Search Results (50,277)

Diabetes mellitus (DM) poses an increasingly high global health burden nowadays, while in adults, chronic kidney disease (CKD) associated with DM impacts 20–40% of those with the condition. Effective management of CKD in patients with diabetes necessitates a comprehensive, multidisciplinary approach. Numerous factors, including glomerular hyperfiltration, oxidative stress, inflammation, and hypoxia are linked to the advancement of diabetic kidney disease (DKD). Currently, no specific treatment for DKD has been established, prompting extensive exploration of new approaches. Renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter 2 inhibitors have demonstrated renoprotective effects in various human clinical trials. Additionally, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists have been reported as effective in managing DKD, while new therapeutic candidates are also under investigation, such as soluble guanylate cyclase activators and aldosterone synthase inhibitors. Recent evidence has shown that treating diabetic nephropathy by reducing albuminuria levels and retarding its progression is a complex skill. The purpose of this review is to support the impressive results that appear in reducing albuminuria and the progression of diabetic nephropathy with early and intensive combination treatment compared to the recently emerged conventional monotherapy, with agents that act on different pathophysiological mechanisms. Full article

CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell–extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural stem/progenitor cells, microglia, astrocytes, and selected neuronal populations. The interactions of CD44 with ligands such as hyaluronan and osteopontin regulate critical cellular functions, including migration, differentiation, inflammation, and synaptic plasticity. In microglia and macrophages, CD44 mediates immune signaling and phagocytic activity, and it is dynamically upregulated in neuroinflammatory diseases, particularly through pathways involving Toll-like receptor 4. CD44 expression in astrocytes is abundant during central nervous system development and in diseases, contributing to glial differentiation, reactive astrogliosis, and scar formation. Though its expression is less prominent in mature neurons, CD44 supports neural plasticity, circuit organization, and injury-induced repair mechanisms. Additionally, its expression at nervous system barriers, such as the blood–brain barrier, underscores its role in regulating vascular permeability during inflammation and ischemia. Collectively, CD44 emerges as a critical integrator of neural cell function and intercellular communication. Although the roles of CD44 in glial cells appear to be similar to those explored in other tissues, the expression of this molecule and its variants on neurons reveals peculiar functions. Elucidating the cell-type-specific roles and regulation of CD44 variants may offer novel therapeutic strategies for diverse neurological disorders. Full article

Hydrogels are water-rich polymeric networks mimicking the body’s extracellular matrix, making them highly biocompatible and ideal for precision medicine. Their “tunable” and “smart” properties enable the precise adjustment of mechanical, chemical, and physical characteristics, allowing responses to specific stimuli such as pH or temperature. These versatile materials offer significant advantages over traditional drug delivery by facilitating targeted, localized, and on-demand therapies. Applications range from diagnostics and wound healing to tissue engineering and, notably, cancer therapy, where they deliver anti-cancer agents directly to tumors, minimizing systemic toxicity. Hydrogels’ design involves careful material selection and crosslinking techniques, which dictate properties like swelling, degradation, and porosity—all crucial for their effectiveness. The development of self-healing, tough, and bio-functional hydrogels represents a significant step forward, promising advanced biomaterials that can actively sense, react to, and engage in complex biological processes for a tailored therapeutic approach. Beyond their mechanical resilience and adaptability, these hydrogels open avenues for next-generation therapies, such as dynamic wound dressings that adapt to healing stages, injectable scaffolds that remodel with growing tissue, or smart drug delivery systems that respond to real-time biochemical cues. Full article

α-Cyclodextrin/Moringin (α-CD/MOR) is an isothiocyanate showing neuroprotective and antioxidant properties. In this work, we studied in differentiated NSC-34 motor neurons cell line the molecular pathways activated following a treatment of 96 h with α-CD/MOR at different doses, namely 0.5, 5 and 10 μM. Taking advantage of comparative transcriptomic analysis, we retrieved the differentially expressed genes (DEGs) and we mapped DEGs to synaptic genes using the SynGO database. Then, we focused on the biological pathways in which they are involved. We observed that the prolonged treatment with α-CD/MOR significantly modulated biological processes and cellular components associated with synaptic organization. Interestingly, the KEGG pathway “Regulation of actin cytoskeleton” was overrepresented, alongside pathways related to synapses and axon guidance. Specifically, SPIA analysis indicated that the “Regulation of actin cytoskeleton” pathway was found to be activated with the highest dose of α-CD/MOR. Moreover, α-CD/MOR also modulated transcription factors involved in synaptic plasticity, such as Creb1. These results could indicate that α-CD/MOR can influence synaptic functions and organization, being involved in synaptic plasticity through the modulation of actin dynamics. Full article

The presence of various Ag species (Ag⁺ ions, Ag clusters, and Ag nanoparticles (NPs)) in Ag-zeolite nanocomposites strongly influences their catalytic, photocatalytic, and antibacterial properties. To tailor materials for specific applications, it is essential to employ strategies that control the redox processes between Ag⁺ and Ag⁰ and facilitate the formation of active Ag-containing composites. In this study, we present a comparative analysis of Ag-zeolite nanocomposites, focusing on their synthesis methods, structural characteristics, and antibacterial activity against Escherichia coli. Ag NPs were synthesized using three approaches: solid-state thermal reduction, chemical reduction in aqueous solutions with a mild reducing agent (sodium citrate, Na₃Cit), and chemical reduction with a strong reducing agent (sodium borohydride, NaBH₄). The resulting materials were characterized by X-ray diffraction (XRD), diffuse reflectance UV–Vis spectroscopy (DR UV–Vis), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM), while antibacterial activity was assessed using biological assays. Microscopic and spectroscopic analyses confirmed the formation of Ag NPs and the co-existence of immobilized Ag⁺ ions within the zeolite framework. The specific influence of the treatment method of Ag⁺-zeolite on the presence of silver species in the nanocomposites and their role in antibacterial properties were evaluated. The highest antibacterial efficiency was observed in the nanocomposite produced by thermal treatment of Ag-exchanged zeolite. Thus, the crucial function of Ag⁺ ions in the mechanism of bacteria cell death was suggested. Full article

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, and key pathways such as neuroinflammation, oxidative stress, and autophagy are believed to significantly contribute to the mechanisms of neurodegeneration. Calpain activation plays a critical role in neuroinflammation and neurodegeneration, as demonstrated by its impact on microglial activation, reactive oxygen species (ROS) production, and neuronal survival. In this study, we investigated the effects of calpain inhibition using calpeptin (CP) and calpain-2-specific inhibitors in cellular and murine models of neuroinflammation and PD. In BV2 microglial cells, LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-6) and chemokines (MCP-1, IP-10) were significantly reduced by CP treatment with a concomitant decrease in ROS generation. Similarly, in VSC-4.1 motoneuron cells, calpain inhibition attenuated IFN-γ-induced ROS production and improved cell viability, demonstrating its neuroprotective effects. Moreover, in a murine MPTP model of PD, calpain inhibition reduced astrogliosis, ROCK2 expression, and levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-7, and IL12p70) and chemokines (MCP-1 and IP-10) in the dorsal striatum and plasma. The specific role of calpain-2 in immune modulation was further highlighted in human microglia, SV-40 cells. With respect to immune modulation in these cells, siRNA-mediated knockdown of calpain-2, but not calpain-1, significantly reduced antigen presentation to CD4+ T cells. Thus, calpain-2 is likely involved in regulating antigen presentation and activation of inflammatory CD4+ T cells. These findings underscore the therapeutic potential of calpain-2 inhibition in mitigating neuroinflammation and neurodegeneration, particularly in PD, by targeting microglial activation, ROS production, and neuronal survival pathways. Full article

Akebia trifoliata is an emerging fruit crop in China, valued for its medicinal and nutritional properties. To elucidate the developmental dynamics of its bioactive compounds, we performed widely targeted metabolomics using Ultra Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) across four fruit developmental stages (S1–S4). A total of 1595 metabolites were identified, of which 988 were differentially accumulated and categorized into three distinct accumulation patterns. Flavonoids and phenolic acids exhibited a marked decline during fruit maturation, corresponding with decreasing antioxidant and α-glucosidase inhibitory activities. Conversely, functional oligopeptides and specific terpenoids accumulated significantly at later stages. K-means clustering revealed dynamic shifts in metabolic profiles, and 23 functional oligopeptides with antioxidative, antidiabetic, and ACE-inhibitory activities (angiotensin-converting enzyme, ACE) were predicted. KEGG enrichment highlighted stage-specific pathway transitions from flavonoid biosynthesis during early development to sugar metabolism at ripening. Correlation analysis identified key flavonoids, phenolic acids, and amino acid derivatives associated with antioxidant capacity and α-glucosidase inhibition. This study provides comprehensive metabolomic landscape of A. trifoliata fruit development and offers valuable insights for its functional exploitation in food and medicinal applications. Full article

Chitosan (CTS) is a biodegradable and biocompatible biopolymer derived from chitin. Thanks to its diverse biological activities and environmentally friendly nature, it has emerged as a promising agent in plant tissue culture. Recent studies have highlighted its role as a natural elicitor that can enhance plant growth, seed germination, and the biosynthesis of secondary metabolites in vitro. In plant tissue culture, it acts as a biotic elicitor, mimicking a pathogen attack and activating the pathogenesis-related proteins to induce secondary metabolite production. In vitro tissue culture is a scientifically meaningful and cost-effective approach to testing the elicitation mechanisms of various abiotic elicitors, including CTS. However, the methodology of CTS elicitation in plant tissue cultures is not straightforward or uniform due to the differences in the CTS origin, molecular weight, and degree of deacetylation, all of which directly affect solubility. This review summarizes the methodological approaches to the use of CTS in plant tissue culture elicitation and highlights specific features of these procedures. Full article

This study evaluated the effects of different doses of the herbicide fluroxypyr on soil microbial communities under controlled laboratory conditions. Specific enzymatic activities ((dehydrogenase (DA), urease (UA), catalase (CA), phosphatase (PA)) and quantitative variations in bacterial and fungal populations were measured regarding key physico-chemical soil parameters (temperature, pH, electrical conductivity, moisture, organic matter, ammonium, nitrate nitrogen, and available phosphate content). The effects of the herbicide on the targeted parameters were dose- and time-dependent. Fluroxypyr induced a clear decrease in DA, CA, and PA during the first 14 days after administration, while UA showed a decrease in the first 7 days, followed by a slight increase starting on day 14, closely related to the applied dose. Microbial populations decreased in direct relation to the fluroxypyr dose. Organic matter content exhibited a positive correlation with DA, UA, CA, as well as with microbial populations. In addition, three natural compounds structurally similar to fluroxypyr were identified via 3D virtual screening, demonstrating potential herbicidal activity. Fluroxypyr can alter soil metabolic activity and disrupt microbial communities, thereby affecting soil fertility. Used as a reference in 3D screening, fluroxypyr helped identify three natural compounds with potential herbicidal activity as safer alternatives to synthetic herbicides. Full article

Context: It has been claimed that recently, in England, the places with the greatest amount of housing built were the places that least needed them. This is an accusation that has echoes in a number of countries around the globe. The lack of construction leads to greater unaffordability and a lower level of economic activity than could have been achieved if labour, particularly those with high human capital, was not so constrained as to where they could afford to live. The recent National Planning Policy Framework for England imposes mandatory targets on housing planning authorities. As such, the following question is raised: will the targets result in additional residential homes being located in places of greater need than the prevailing pattern? Research Questions: The paper sets out to consider the spatial mismatch between housing additions and national benefit in terms of unaffordability and productivity. Specifically, do the concentrations of high and/or low rates of the prevailing rates of additional dwellings and the target rates of adding dwellings correspond with the clusters of high and/or low unaffordability and productivity? A further question considered is: does the spatial distribution of additional dwellings match the clusters of population growth? Method: The values of the variables are transformed at the first stage into Anselin’s LISA categories. LISA maps can reveal unusually high spatial concentrations of values, or clusters. The second stage entails comparing sets of the transformed data for agreement of the classifications. An agreement coefficient is provided by Fleiss’s kappa. Data: The data used is of additional dwellings, the total number of dwellings, population estimates, gross value added per hour worked (productivity data), and house price–earnings ratios. The period of study covers the eight years prior to 2020 and the two years after, omitting 2020 itself due to the unusual impact on economic activity. All the data is at local authority district level. Findings: The hot and cold spots of additional dwellings do not correspond those of house price–earnings ratios or productivity. However, population growth hot spots show moderate agreement with those of where additional dwellings are concentrated. This is in line with findings from elsewhere, suggesting that population follows housing supply. Concentrations of districts with relatively high targets per unit of existing stocks are found correspond (agree strongly) with clusters of house price–earnings ratios. Links between productivity and housing are much weaker. Conclusions: The strong link between targets and affordability suggests that if the targets are met, the claim that the places that build the most housing are the places that least need them can be challenged. That said, house-price–earnings ratios present a view of unaffordability that will favour greater building in the countryside rather than cities outside of London, which runs against concentrating new housing in urban areas consistent with fostering clusters/agglomerations implicit in the new modern industrial strategy. Full article

Background/Objectives: Pediatric acquired brain injury (ABI) often results in persistent challenges that extend beyond motor impairments, affecting quality of life (QoL), social participation, and engagement in physical activity. Given the complexity and chronicity of these outcomes, there is a pressing need for multidimensional interventions grounded in the International Classification of Functioning, Disability and Health (ICF). Sport-based exercise interventions, when developmentally adapted and tailored to individual interests, may promote intrinsic motivation, peer connection, and sustainable engagement—factors especially relevant in pediatric ABI populations, who often experience reduced physical activity and social isolation. However, standardized, replicable protocols specifically tailored to this population remain scarce. This study presents the protocol for a randomized controlled trial evaluating the effects of a 16-week sport-based intervention on QoL, social participation, physical activity engagement, and motor functioning tailored for adolescents with pediatric ABI. Methods: Participants will be randomly assigned to an intervention group or a control group receiving usual care. The intervention consists of one weekly 60-minute session, led by trained professionals in adapted physical activity and pediatric neurorehabilitation. It combines sport-based motor skill training, cooperative games, and group activities specifically tailored to each child’s developmental level, motor abilities, and preferences. Outcomes will be assessed at baseline and following the 16-week intervention period, focusing on QoL, participation, physical activity engagement, and motor functioning. Discussion: This study introduces a structured, child-centered model that bridges clinical rehabilitation and community-based sport. By integrating motor and psychosocial targets through a group sport-based intervention, it aims to enhance recovery across ICF domains. Findings may inform interdisciplinary practice and support the development of sustainable strategies to promote long-term engagement and well-being in adolescents with ABI. Full article

Fast fashion is a rapidly expanding sector characterized by high production volumes, low costs, and short product lifecycles. While recent efforts have focused on improving sustainability within supply chains, consumer behavior remains a critical yet underexplored driver of environmental impacts. This study presents a web-based calculator tool designed to estimate both the carbon and plastic footprints associated with individual fast fashion consumption, with a particular focus on shopping behaviors, garment disposal, and laundry habits. Adopting a geographical perspective, the analysis explicitly considers the spatial dynamics of consumption and logistics within the urban context of Milan (Italy), a dense metropolitan area representative of high fashion activity and mobility. By incorporating user-reported travel patterns, logistics routes, and localized emission factors, the tool links consumer habits to place-specific environmental impacts. By involving over 360 users, the tool not only quantifies emissions and plastic waste (including microfibers) but also serves an educational function, raising awareness about the hidden consequences of fashion-related choices. Results reveal high variability in environmental impacts depending on user profiles and behaviors, with online shopping, frequent use of private vehicles, and improper garment disposal contributing significantly to emissions and plastic pollution. Our findings highlight the importance of integrating consumer-focused educational tools into broader sustainability strategies. The tool’s dual function as both calculator and awareness-raising platform suggests its potential value for educational and policy initiatives aimed at promoting more sustainable fashion consumption patterns. Full article

Aim: To investigate the synergistic effects of exercise training and Brassica oleracea var. italica (broccoli sprout) supplementation on Apolipoprotein A-I, B-100, and J levels in men with Type 2 diabetes mellitus (T2DM). Methods: Forty-four males with T2DM were randomly assigned to four groups: Control (CG), Supplement (SG), Training (TG), and Training + Supplement (TSG) groups. Participants in the supplement groups (SG and TSG) received 10 g of broccoli supplement after meals for 12 weeks, while those in the training groups (TG and TSG) participated in a structured exercise program (resistance and aerobic), performed three times per week for 12 weeks, at intensities of 60–70% one-repetition maximum (1RM) for resistance training and 60–70% peak oxygen uptake (VO_2peak) for aerobic training. Results: Circulating levels of apolipoproteins improved after 12 weeks in the TSG, TG, and SG groups. However, the TSG group exhibited the most pronounced improvements across metabolic and lipoprotein markers, reflecting an additive effect of both interventions. Specifically, the TSG group demonstrated absolute reductions in ApoB-100 (−48.30 ± 7.20 mg/dL) and ApoJ (−44.05 ± 5.76 mg/dL), along with an increase in ApoA-I (+44.92 ± 6.05 mg/dL). Main effect analysis revealed that exercise training elicited the most substantial improvements across metabolic and lipoprotein markers, with large effect sizes for glucose (η²p = 0.787), insulin (η²p = 0.640), HOMA-IR (η²p = 0.856), ApoA-I (η²p = 0.685), ApoB-100 (η²p = 0.774), ApoJ (η²p = 0.848), and HDL-C (η²p = 0.535). Supplementation showed moderate effects, particularly on HOMA-IR (η²p = 0.370), ApoA-I (η²p = 0.383), and ApoB-100 (η²p = 0.334), supporting an additive but exercise-dominant benefit. The combined intervention group (TSG) showed the most pronounced improvements across all measured outcomes, with large effect sizes for ApoA-I (η²p = 0.883), glucose (η²p = 0.946), insulin (η²p = 0.881), HOMA-IR (η²p = 0.904), and ApoJ (η²p = 0.852). Conclusions: The effects of combining training and broccoli sprout supplementation on apolipoprotein levels are likely to result from the activation of two separate pathways, one from training and the other from supplementation. This dual-modality intervention could serve as an effective complementary strategy in managing metabolic and cardiovascular risk factors for individuals with T2DM. However, the magnitude of change induced by the combination of exercise training and broccoli supplementation was largely driven by the training component, with supplementation providing complementary but less consistent benefits. Full article

:Solvents represent the quiet majority in biomolecular systems, yet modeling their influence with both speed and ri:gor remains a central challenge. This study maps the state of the art in implicit solvent theory and practice, spanning classical continuum electrostatics (PB/GB; DelPhi, APBS), modern nonpolar and cavity/dispersion treatments, and quantum–continuum models (PCM, COSMO/COSMO-RS, SMx/SMD). We highlight where these methods excel and where they falter, namely, around ion specificity, heterogeneous interfaces, entropic effects, and parameter sensitivity. We then spotlight two fast-moving frontiers that raise both accuracy and throughput: machine learning-augmented approaches that serve as PB-accurate surrogates, learn solvent-averaged potentials for MD, or supply residual corrections to GB/PB baselines, and quantum-centric workflows that couple continuum solvation methods, such as IEF-PCM, to sampling on real quantum hardware, pointing toward realistic solution-phase electronic structures at emerging scales. Applications across protein–ligand binding, nucleic acids, and intrinsically disordered proteins illustrate how implicit models enable rapid hypothesis testing, large design sweeps, and long-time sampling. Our perspective argues for hybridization as a best practice, meaning continuum cores refined by improved physics, such as multipolar water, ML correctors with uncertainty quantification and active learning, and quantum–continuum modules for chemically demanding steps. Full article

This study aims to assess the role of headwater systems (HS) in enhancing ecological connectivity and supporting Green Infrastructure in the Centre Region of Portugal. Specifically, it identifies restoration opportunity areas within HS by analysing land-use changes over the past 70 years, modelling land-use scenarios to promote ecological resilience, and evaluating connectivity between HS and Natura 2000 sites. The methodology integrates spatial analysis of historical land-use data with connectivity modelling using least-cost path approaches. Results show substantial transformation in HS areas, notably the expansion of eucalyptus plantations and a decline in agricultural land. Approximately 58% of the HS are identified as requiring restoration, including areas within the Natura 2000 network. The connectivity assessment reveals that HS can function as effective ecological corridors, contributing to improved water regulation, soil conservation, gene flow, and wildfire mitigation. A total of 61 potential ecological linkages between Natura 2000 sites were identified. These findings highlight the strategic importance of integrating HS into regional and national Green Infrastructure planning and supporting the implementation of the EU Biodiversity Strategy for 2030. The study recommends prioritising headwater restoration through multi-scale planning approaches and active involvement of local stakeholders to ensure sustainable land-use management. Full article