Search Results (3,055)

Swarm Intelligence (SI) algorithms were applied widely in solving complex optimization problems because they are simple, flexible, and efficient. The current paper proposes a new SI algorithm, which is based on the bird-like actions of swallows, which have highly synchronized behaviors of foraging and migration. The optimization algorithm (SWSO) makes use of these behaviors to boost the ability of exploration and exploitation in the optimization process. Unlike other birds, swallows are known to be so precise when performing fast directional alterations and making intricate aerial acrobatics during foraging. Moreover, the flight patterns of swallows are very efficient; they have extensive capabilities to transition between flapping and gliding with ease to save energy over long distances during migration. This allows instantaneous changes of wing shape variations to optimize performance in any number of flying conditions. The model used by the SWSO algorithm combines these biologically inspired flight dynamics into a new computational model that is aimed at enhancing search performance in rugged terrain. The design of the algorithm simulates the swallow’s social behavior and energy-saving behavior, converting it into exploration, exploitation, control mechanisms, and convergence control. In order to verify its effectiveness, (SWSO) is applied to many benchmark problems, such as unimodal, multimodal, fixed-dimension functions, and a benchmark CEC2019, which consists of some of the most widely used benchmark functions. Comparative tests are conducted against more than 30 metaheuristic algorithms that are regarded as state-of-the-art, developed so far, including PSO, MFO, WOA, GWO, and GA, among others. The measures of performance included best fitness, rate of convergence, robustness, and statistical significance. Moreover, the use of (SWSO) in solving real-life engineering design problems is used to prove (SWSO)’s practicality and generality. The results confirm that the proposed algorithm offers a competitive and reliable solution methodology, making it a valuable addition to the field of swarm-based optimization. Full article

Reprogramming is recognized as a promising target in cancer therapy. It is well known that the altered metabolism in cancer cells, in particular malignancies, are characterized by increased aerobic glycolysis (Warburg effect) which promotes rapid proliferation. The effort to design compounds able to modulate these hallmarks of cancer are gaining increasing attention in drug discovery. In this context, the present review explores recent progress in the development of small molecule inhibitors of key metabolic pathways, such as glycolysis, glutamine metabolism and fatty acid synthesis. In particular, different mechanisms of action of these compounds are analyzed, which can target distinct enzymes, including LDH, HK2, PKM2, GLS and FASN. The findings underscore the relevance of metabolism-based strategies in developing next-generation anticancer agents with potential for improved efficacy and reduced systemic toxicity. Full article

The inherent complexity of modern supply chains obscures significant hidden CO₂ and Water Pollution Equivalent (WPE) emissions, presenting mounting challenges for integrated environmental governance. While prior research has largely treated carbon and water pollution metabolic systems in isolation, this study addresses the critical gap in understanding their bidirectional interactions under socioeconomic dynamics. We develop a novel Three-Dimensional Evaluation Method for the Metabolic Interaction System of Industrial CO₂ and Water Pollution (TDE-ISCW). This framework integrates Environmental Input–Output Analysis and Ecological Network Analysis to: (1) identify key industrial sectors and utility relationships within individual CO₂ and WPE systems; (2) quantify the mutual disturbance responses between the CO₂ and WPE metabolic systems through changes in sectoral emissions/output, inter-sectoral relationships, and sector–system linkages; and (3) propose optimized industrial restructuring strategies for synergistic pollution and carbon reduction. Applied to the highly industrialized Yangtze River Economic Belt, key findings reveal: (i) substantial upstream dependency, exemplified by Advanced Equipment Manufacturing’s 95.7% indirect CO₂ emissions; (ii) distinct key sectors for CO₂ (e.g., MOO, FTO, MNM) and WPE (e.g., MPM, OTH, FTO) reduction based on competitive relationships; and (iii) complex trade-offs, where emission reductions in one system (e.g., CO₂ via FTO restructuring) can trigger heterogeneous responses in the other (e.g., altered WPE influence or downstream CO₂/economic shifts). The TDE-ISCW framework provides actionable insights for designing coordinated, adaptive emission reduction policies that account for cascading cross-system effects, ultimately supporting regional industrial upgrading and resource efficiency goals. Future research should incorporate temporal dynamics and full industrial–metabolic cycles. Full article

In the Mexican Caribbean, the demand for tourism services led to the expansion of the hotel industry from the coast inland. This caused rural and urban communities in the region to become involved in tourism activities, initiating the formulation of an international model of sustainable development with a focus on cultural tourism. Considering the tourism potential that the study area can offer to nearby rural communities, as well as the limited number of studies aimed at estimating tourism carrying capacity (see examples of TCC for environmental management units in communal land areas like Baja California, Mexico and the Huagapo cave in Peru), the present research aims at estimating the tourism carrying capacity in the southern region of the Mexican Caribbean. A mixed methodological approach was adopted for the present study entailing a detailed description of flora and fauna in the study area using natural resource mapping tools, social diagnosis of the communities in the study area using the Participatory Action Research (PAR) technique in the communities of Caobas and San José de la Montaña and the estimation of tourism carrying capacity (TCC), Physical Carrying Capacity (PCC), Real Carrying Capacity (RCC), and Effective Carrying Capacity (ECC) using information gathered through fieldwork and bibliographic review. It was found that the area can support a tourism carrying capacity of 538.33 visits per day. In this initial assessment, it was estimated that the implementation of an ecotourism project in a rural community would not alter its environmental conditions. The estimated indicators provide appropriate tools for designing and planning long-term sustainable tourism proposals. Moreover, they integrate environmental, economic, and social aspects in a balanced manner, generating tangible and lasting benefits. Full article

Amphibians are particularly vulnerable to hydric stress due to their permeable skin, biphasic life cycle, and strong dependence on aquatic and moist terrestrial environments. In the Northwestern Mediterranean Basin—one of Europe’s most climate-sensitive regions—the intensification of droughts associated with climate change poses a critical threat to amphibian populations. Increased aridification, either due to higher temperatures or to more frequent, prolonged, and severe drought episodes, can affect both aquatic and terrestrial life stages, directly altering breeding opportunities, larval development, post-metamorphic survival, and dispersal capacity. This review aims to gather and synthesize current knowledge on the ecological, physiological, and demographic impacts of drought on amphibians of the Northwestern Mediterranean across habitat types, including ephemeral ponds, permanent water bodies, lotic systems, and terrestrial landscapes, including a final section on possible mitigation actions. Drought-induced shifts in hydroperiod can drastically reduce reproductive success and accelerate larval development with fitness consequences while, on land, desiccation risk and habitat degradation could limit access to refugia and fragment populations by reducing structural connectivity. These environmental constraints are compounded by the interactions between drought and emerging infectious diseases. We discuss the current knowledge on how chytrid fungi (Batrachochytrium dendrobatidis and B. salamandrivorans) and ranaviruses may respond to temperature and moisture regimes, and how drought may affect their transmission dynamics, host susceptibility, and pathogen persistence. In these cases, microbiome disruption, pollutant concentration, and increased contact rates between species may amplify disease outbreaks under dry conditions, but a better understanding of the multifactorial effects of drought on amphibian biology and disease ecology is needed for predicting species vulnerability, identifying high-risk populations, and guiding future conservation and management strategies in Mediterranean environments. Full article

Lactylation, a recently identified post-translational modification (PTM) triggered by excessive lactate accumulation, has emerged as a crucial regulator linking metabolic reprogramming to pathological processes in liver diseases. In hepatic contexts, aberrant lactylation contributes to a range of pathological processes, including inflammation, dysregulation of lipid metabolism, angiogenesis, and fibrosis. Importantly, lactylation has been shown to impact tumor growth, metastasis, and therapy resistance by modulating oncogene expression, metabolic adaptation, stemness, angiogenesis, and altering the tumor microenvironment (TME). This review synthesizes current knowledge on the biochemical mechanisms of lactylation, encompassing both enzymatic and non-enzymatic pathways, and its roles in specific liver diseases. From a therapeutic perspective, targeting lactate availability and transport, as well as the enzymes regulating lactylation, has demonstrated promise in preclinical models. Additionally, combinatorial approaches and natural compounds have shown efficacy in disrupting lactylation-driven pathways, providing insights into future research directions for hepatic diseases. Although the emerging role of lactylation is gaining attention, its spatiotemporal dynamics and potential for clinical translation are not yet well comprehended. This review aims to synthesize the multifaceted roles of lactylation, thereby bridging mechanistic insights with actionable therapeutic strategies for liver diseases. Full article

Cisplatin (CIS)-induced peripheral neuropathy and associated comorbidities have a detrimental effect on the lives of cancer patients. Currently, there are no effective therapies to alleviate these symptoms. Duloxetine (DULO) is a recommended treatment, but it is linked with important side effects, thus making it essential to explore novel approaches. We examined the impact of a prophylactic treatment with a low dose of DULO combined with hydrogen-rich water (HRW) on CIS-injected C57BL/6 male and female mice as a possible therapy for allodynia, muscle and body weight deficits, and emotive syndromes accompanying this type of chemotherapy. The prophylactic treatment with DULO and HRW prevented mechanical allodynia caused by CIS in both sexes and had greater effects than either treatment given individually. The combined treatment also prevented cold allodynia in male mice but only reduced it in females. Moreover, the coadministration of DULO with HRW avoided muscular deficits in both sexes. Furthermore, the body weight reduction induced by CIS in both sexes was not entirely mitigated by the combined therapy. However, all treatments avoided the anxiety- and depressive-like behaviors elicited by CIS. The antiallodynic actions and prevention of muscular deficits produced by the combined treatment might be explained by the inhibition of oxidative stress, inflammatory responses, and plasticity alterations provoked by CIS in the dorsal root ganglia of these subjects. This study proposes, for the first time, the cotreatment of DULO with HRW as an effective therapy for CIS-induced peripheral neuropathy and reveals the influence of sex on these actions. Full article

The bulk linearization technique is a design strategy used to extend the linear region of a metal oxide semiconductor field effect transistor (MOSFET) by increasing its saturation voltage through a composite structure and a gate biasing circuit. This allows us to develop compact and flexible pseudo-resistor elements for integrated circuit designs. In this paper we propose a new simple yet effective design approach, focused on the biasing circuit, that optimizes area, offset, and power consumption without altering the design complexity of the original solution. Post-layout simulations verify the presented design strategy, which is then applied for designing a band-pass filter for neural action potential acquisition. Results of harmonic distortion and noise analysis strengthen the validity of the proposed strategy. Full article

This study aimed to investigate the cytological and biochemical effects of tyrosol on bronchoalveolar lavage fluid (BALF) in an experimental lung injury model induced via intratracheal bleomycin (BLM) administration at 4 mg/kg. Tyrosol is a compound found in olive oil with antioxidant, anti-inflammatory, and antifibrotic activity, and there are no publications on its effect on broncho-alveolar lavage. A total of fifty male Sprague Dawley rats were randomly divided into five groups: control, BLM only, and BLM combined with tyrosol at doses of 20, 40, and 80 mg/kg. Following a two-week treatment period, BALF samples were collected and evaluated cytologically and biochemically. BLM administration led to significant increases in the proportions of lymphocytes, neutrophils, and epithelial cells (p < 0.05) and a decrease in macrophage percentages in BALF. Tyrosol treatment modulated these cellular alterations in a dose-dependent manner, with notable increases in macrophage ratios and reductions in inflammatory cells, particularly at 40 and 80 mg/kg doses. Furthermore, the presence of foamy macrophages—commonly observed in the BLM group—was found to decrease in a dose-dependent manner with tyrosol administration. Biochemical analyses showed that BLM significantly elevated malondialdehyde (MDA) levels (p < 0.05), while reducing the levels of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). Tyrosol treatment improved these parameters in a dose-dependent manner, thereby reducing oxidative stress. In cytokine analysis, BLM increased all proinflammatory cytokine levels, whereas tyrosol treatment, particularly at higher doses, significantly decreased IL-6 levels (p < 0.05). In conclusion, tyrosol demonstrated notable protective effects against bleomycin-induced lung injury by exerting anti-inflammatory and antioxidative actions at the BALF level. Full article

This study reviews existing research on the effects of the interaction between in-plane (IP) and out-of-plane (OOP) behaviors on the seismic response of non-framed unreinforced masonry (URM) structures. During earthquakes, masonry buildings exhibit complex behaviors. First, walls may experience simultaneous IP and OOP actions, or pre-existing IP and OOP damage, deformation, or loads that can alter their unidirectional IP or OOP seismic response. Second, the IP and OOP action of one wall can affect the behavior of its intersecting walls. However, the effects of these behaviors, referred to as “direct IP-OOP interactions” and “Flange effects”, respectively, are often disregarded in design and assessment provisions. To address this gap, this study explores findings from experimental and numerical research conducted at the wall level currently available in the literature, identifying the nature of these interaction effects and the key parameters that affect their extent. The available body of work includes only a few experimental studies on interaction effects, whereas numerical investigations are more extensive. However, most numerical studies focus on how OOP pre-damage/deformation influences the IP behaviors (OOP/IP interactions) and the role of flanges in IP response (F/IP interactions), leaving significant gaps in understanding the effects of IP pre-damage/deformation on the OOP response (IP/OOP interactions) and the OOP response in the presence of flanges (F/OOP interactions). Among the parameters studied, boundary conditions, wall height-to-length aspect ratio, and vertical overburden are found to have the most significant influence on interaction effects because of their relevance for the IP and OOP failure mechanisms. Other parameters, such as the restriction of top uplift, the presence of openings, or changes in slenderness ratio, are not comprehensively studied, and the available data are insufficient for definitive conclusions. Methodologies available in the literature for extrapolating the findings observed at the wall level to building-level analyses are reviewed. The current predictive equations primarily address the effects of OOP pre-load and Flange effects on IP response. Furthermore, only a few macro-element models are proposed for cost-effective, large-scale building simulations. To bridge these gaps, future research must expand experimental investigations, develop more comprehensive design and assessment equations, and refine numerical modeling techniques for building-level applications. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) constitutes a significant and progressive liver disease, characterized by a complex pathogenesis that involves dysbiosis of the gut microbiota. While the multifaceted nature of MASH is widely recognized, its underlying mechanisms remain the subject of active investigation. Contemporary research highlights the critical role of the gut–liver axis, suggesting that disturbances in the gut microbiome may contribute to the progression of the disease. Probiotics have notably emerged as a promising therapeutic approach for MASH, with the potential to modulate the gut microbiome and mitigate symptoms. This review aims to examine the alterations in the gut microbiome associated with MASH pathogenesis, the interaction of probiotics with the gut–liver axis, and their significance in the development and management of MASH. By synthesizing current evidence on the mechanisms of action of probiotics, clinical trials, and comparative efficacy of different strains, as well as existing controversies, challenges, and future research directions, this review seeks to establish a scientific foundation for probiotic-based interventions as an innovative therapeutic strategy for MASH. Full article

The EU’s Circular Economy Action Plan promotes the use of organic waste as fertilizer, thus allowing the recycling of nutrients in the agricultural system. Research on the agronomic reuse of composted substrates previously employed for mushroom cultivation remains limited, despite their rich content of plant residues and fungal biomass, which could be repurposed as soil amendments under suitable conditions. This study evaluated the agronomic potential of spent mushroom substrates from Agaricus bisporus and Pleurotus ostreatus, including recomposted A. bisporus residues. A range of analytical procedures was employed to assess their suitability for soil improvement and the formation of humic-like substances, including physical, chemical, microbiological, phytotoxicity, and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) analyses. The spent Pleurotus substrate exhibited low nutrient content (1.1% N, negligible P, 0.9% K), but high water retention (820 kg water Mg⁻¹) and 48% organic carbon (OC), indicating its potential as a soil amendment or seedling substrate. In contrast, spent and composted Agaricus substrates showed moderate nutrient content (1.8–2.7% N; 0.8–0.7% P and 1.3–1.8% K), appropriate C/N ratios (10–15), and sufficient OC levels (24–30%), supporting their use as fertilizers. However, elevated salinity levels (18–23 dS m⁻¹) may restrict their application for salt-sensitive crops. No significant phytotoxic effects on seed germination were observed, and microbiological analyses confirmed the absence of Salmonella spp. in the three substrates. Py-GC/MS revealed a humic acid-like fraction comprising altered lignin structures enriched with lipid and nitrogen compounds. Overall, the studied materials demonstrate promising agronomic value and the capacity to contribute to long-term soil carbon storage. Full article

Cytochrome P450 (CYP450) enzymes play an essential role in the metabolism of drugs, particularly in phase I metabolic reactions. In this article, we present a comprehensive review of fifteen selected enzymes belonging to the CYP450 family. The enzymes included in this analysis are CYP7A1, CYP3A4, CYP3A5, CYP2D6, CYP2E1, CYP2C8, CYP2C18, CYP2C9, CYP2C19, CYP2B6, CYP2A6, CYP2A13, CYP1B1, CYP1A1, and CYP1A2. We examined the influence of natural, polymorphic variations within their primary amino acid sequences on their enzymatic function and mechanisms of action. To begin, we compiled a dataset of naturally occurring polymorphic variants for these enzymes. This was achieved through a detailed analysis of entries in the UniProt database, as well as an extensive review of the current scientific literature. For each variant, we included commentary regarding its potential impact on enzyme activity or drug response, based on evidence observed in in vitro experiments, in vivo studies, or clinical trials. Particular emphasis was placed on how such polymorphisms might alter the metabolism of xenobiotics, thereby potentially affecting pharmacological outcomes. In this respect, the work represents the first comprehensive source in the scientific literature that systematically gathers and organizes data on CYP450 polymorphisms, including an assessment of their potential significance in processes mediated by these enzymes. A more detailed comparison of the polymorphism-related in vitro studies is devoted to CYP3A4, an enzyme that displays the largest fraction of clinically significant polymorphs. Secondly, we aimed to establish possible molecular explanations for why specific polymorphisms exhibit clinically or experimentally observable effects. To explore this, we performed a qualitative structural analysis of the enzymes, focusing on shared structural characteristics among the examined members of the CYP450 family. The results of this analysis demonstrate that there is no single universal mechanism by which polymorphisms influence the function of CYP450 enzymes. Instead, the mechanisms vary and may include alterations in the orientation of the enzyme within the lipid membrane, changes affecting the association or dissociation of substrates and products at the active site, structural stabilization or destabilization of the enzyme’s reactive centers, modifications in the way the enzyme interacts with its ligand, or alterations in the character of the interface involved in contact with its redox partner (electron transfer protein). Furthermore, among the polymorphisms that significantly impact enzyme function, mutations involving the substitution of arginine residues for other amino acids appear to be overrepresented. Full article

This study used NMR-based metabolomics to investigate the mode of action (MoA) of 6-hydroxydopamine (6-OHDA) toxicity in the SH-SY5Y neuroblastoma cell model. 6-OHDA, a structural analogue of dopamine, has been used to create a Parkinson’s disease model since 1968. Its selective uptake via catecholaminergic transporters leads to intracellular oxidative stress and mitochondrial dysfunction. SH-SY5Y cells were treated with 6-OHDA at its IC₅₀ concentration of 60 μM, and samples of treated and untreated groups were collected after 24 h. The endo metabolome was extracted using a methanol–water mixture, while the exo metabolome was represented by the culture media. Further, endo- and exo metabolomes of treated and untreated cells were analysed for metabolic changes. Our results demonstrated significantly high levels of glutathione, acetate, propionate, and NAD⁺, which are oxidative stress markers, enhanced due to ROS production in the system. In addition, alteration of myoinositol, taurine, and o-phosphocholine could be due to oxidative stress-induced membrane potential disturbance. Mitochondrial complex I inhibition causes electron transport chain (ETC) dysfunction. Changes in key metabolites of glycolysis and energy metabolism, such as glucose, pyruvate, lactate, creatine, creatine phosphate, glycine, and methionine, respectively, demonstrated ETC dysfunction. We also identified changes in amino acids such as glutamine, glutamate, and proline, followed by nucleotide metabolism such as uridine and uridine monophosphate levels, which were decreased in the treated group. Full article

Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive malignancies, with dismal survival rates. Cannabinoids have shown anticancer properties in various cancers, including PDAC. This study aimed to evaluate the anticancer effects of cannabinoids, individually and in combination, and to elucidate their mechanisms of action in a murine PDAC model (KPC mice, KRASWT/G12D/TP53WT/R172H/Pdx1-Cre+/+) that mimics human disease. Additionally, the study explored the potential link between cannabinoid action, gut microbiota modulation, and bile acid (BA) metabolism. PDAC cell lines and KPC mice were treated with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), either as monotherapy or in combination. Faecal pellets, caecal contents, plasma, and tissues were collected at the survival endpoint for analysis. BA profiling was performed using mass spectrometry, and the faecal microbiota was characterised by sequencing the V3-V4 region of the 16S rRNA gene. While CBD and THC synergistically reduced cell viability in PDAC cell lines, only CBD monotherapy improved survival in KPC mice. Extended survival with CBD was accompanied by changes in gut microbiota composition and BA metabolism, suggesting a possible association. Notably, the effects of CBD were different from those observed with THC alone or in combination with CBD. The study highlights a distinct role for CBD in altering BA profiles, suggesting these changes may predict responses to cannabidiol in PDAC models. Furthermore, the findings propose that targeting BA metabolism could offer a novel therapeutic strategy for PDAC. Full article