Search Results (36,577)

Background/Objectives: Ultraviolet (UV) radiation is a major environmental carcinogen responsible for skin damage through oxidative stress, DNA damage, and inflammation. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a central role in regulating cellular antioxidant defences against UV-induced damage. This scoping review aims to evaluate the potential role of sulforaphane (SFN), a known Nrf2 inducer, in protecting against UV-induced skin damage and photocarcinogenesis. Methods: A literature search was conducted in PubMed and Scopus from inception to 27 January 2026, to identify original experimental studies investigating SFN, glucoraphanin, or broccoli sprout extracts in the context of UV-induced skin damage. Eligible studies included in vitro, ex vivo, in vivo, and human models assessing outcomes related to oxidative stress, inflammation, molecular signalling pathways, and tumour development. Following screening and eligibility assessment, twelve studies were included in the qualitative synthesis. Results: The included studies suggest that SFN exerts photoprotective effects across multiple experimental models. In murine studies, SFN and SFN-rich extracts were associated with a reduction in tumour incidence, multiplicity, and volume following UV exposure. In human studies, topical SFN application reduced UV-induced erythema and induced cytoprotective enzyme expression, although clinical evidence remains limited. Mechanistically, SFN consistently activated the Nrf2 pathway, leading to increased expression of antioxidant and phase II detoxifying enzymes, and was associated with modulation of inflammatory responses and inhibition of MAPK/AP-1 signalling. Emerging evidence also indicates potential effects on UV-induced metabolic and epigenetic alterations. Conclusions: Current evidence supports a potential role for sulforaphane in mitigating UV-induced skin damage through activation of endogenous defence pathways. However, the available data are predominantly preclinical, and further well-designed clinical studies are needed to clarify its efficacy and translational relevance in humans. Full article

Endothelial cells (ECs) play a critical role in physiological processes, including regulating blood fluidity, angiogenesis, and regulating the immune response. Integrins, which participate in sensing external stimuli and signal transduction, are crucial for the proper functioning of ECs. Like other cells, ECs undergo senescence, which is associated with their dysfunction and contributes to increased susceptibility to cardiovascular disease. However, the role of integrin-dependent pathways in endothelial senescence is poorly understood. Here, we identify integrin-linked kinase (ILK) as a crucial factor modulating endothelial function and senescence. Using two complementary models, replicative and stress-induced premature senescence, in endothelial cells of different origins, we show that the senescent endothelium shows phenotypic and functional dysfunction. Furthermore, we revealed that these modulations correlated with ILK downregulation. Functionally, ILK depletion in young ECs was sufficient to trigger a senescence-associated phenotype and manifested key features of endothelial dysfunction. In line with this, ILK restoration in senescent cells reduced selected senescence markers and improved endothelial function. Together, these findings show that ILK is not only correlated with endothelial ageing but also works as an active regulator of senescence-linked endothelial dysfunction. Thus, ILK, as a link between adhesion-dependent signalling and endothelial ageing, is a potential target for limiting age-associated vascular decline. Full article

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and interconnected roles in controlling cell survival and mitochondrial integrity. In recent years, naturally occurring flavonoids have attracted considerable attention as potential modulators of these pathways due to their diverse biological activities and relatively low toxicity. This review provides a focused and integrative overview of how different subclasses of flavonoids modulate the p53–Bcl-2 signaling axis to regulate apoptosis in cancer cells. Particular emphasis is placed on the mechanistic interplay between p53 stabilization, transcriptional regulation of apoptotic targets, mitochondrial outer membrane permeabilization, and caspase activation. In contrast to previous general reviews on flavonoids and cancer, this work provides an integrated overview of evidence across multiple flavonoid subclasses and experimental cancer models, highlighting both shared and pathway-specific apoptotic responses. Experimental findings from in vitro and in vivo studies are discussed, including the effects of quercetin, kaempferol, myricetin, epigallocatechin gallate, and related compounds on cell-cycle arrest, oxidative stress, mitochondrial dysfunction, and intrinsic apoptotic signaling. Furthermore, the review examines the relationship between flavonoid chemical structure and biological activity, with particular attention to bioavailability, metabolic transformation, and strategies aimed at improving therapeutic efficacy, including structural modification and nanocarrier-based delivery systems. Despite promising preclinical findings, significant translational challenges remain, including poor pharmacokinetic properties, variability among experimental models, and limited clinical validation. Overall, flavonoids represent a promising class of bioactive compounds capable of targeting apoptosis through modulation of the p53–Bcl-2 network, and a deeper mechanistic understanding of their activity may support the development of novel targeted and combination anticancer therapies. Full article

Forests of Lualaba Province (DR Congo) form a compositionally complex mosaic of dry dense forest, gallery forest, and Miombo woodland. Yet, categorical land-cover maps impose discrete boundaries on these inherently continuous vegetation gradients, systematically discarding subpixel compositional information critical for forest monitoring and carbon accounting. The magnitude of this information loss at the landscape scale, however, remains largely unquantified. In this study, we train a Multi-Output Neural Network (MONN) using Sentinel-2 spectral and textural predictors (2025) to estimate the proportional cover of three forest types across the province. Model performance is benchmarked against a normalised Random Forest (RF) using spatial block cross-validation. Categorical information loss is quantified pixel-wise using two complementary metrics, dominant class proportion and Shannon compositional entropy, alongside a derived interpretive quantity, categorical information loss. The MONN slightly outperformed RF (R² = 0.648 vs. 0.630; RMSE = 0.224 vs. 0.229), yet the results reveal a fundamentally heterogeneous landscape structure. The mean dominant-class proportion was only 56.2%, indicating that categorical maps discard, on average, 43.8% of compositional information per pixel. Only 7.9% of forested pixels exceeded the 75% dominance threshold, while Shannon entropy reached 74.1% of its theoretical maximum, indicating that forest types coexist in near-equal proportions across most pixels. This renders categorical attribution structurally inadequate for most of the forested landscape. Across 92.1% of forested pixels, no single forest type achieved clear dominance. These results show that compositional mixing is the dominant structural condition of the landscape, and that compositional mapping is essential for representing tropical forest structure in heterogeneous drylands. By formally quantifying categorical information loss at the landscape scale, this study shows that continuous compositional mapping converts this structural ambiguity into a spatially explicit ecological signal, with direct implications for monitoring vegetation dynamics and biodiversity, suggesting a structural source of error in carbon stock estimation in tropical dry forests that warrants empirical validation. Full article

Basonuclin 2 (BNC2) is a highly conserved cysteine–histidine (C2H2)-type zinc-finger nuclear regulatory protein characterized by three pairs of zinc-finger domains, a putative nuclear localization signal, a serine-rich region, broad tissue distribution, and remarkable transcript diversity generated through alternative promoter usage, alternative splicing, and polyadenylation. Increasing evidence from human genetics, animal models, functional genomics, and transcriptomic studies indicates that BNC2 links nuclear regulatory mechanisms to tissue-specific developmental and disease phenotypes. In the nervous system, BNC2-positive neuronal populations and BNC2-derived circular RNAs have been implicated in energy-balance circuits and neuroinflammatory regulation. In the skeletal system, BNC2 contributes to osteochondral development, periosteal stem-cell activation, chromatin remodeling, fracture repair, and genetic susceptibility to adolescent idiopathic scoliosis. BNC2 variants have also been associated with congenital lower urinary tract obstruction, whereas its expression and regulatory landscape are closely related to germ-cell development, epithelial ovarian cancer susceptibility, pigmentation traits, fibrosis, and several tumor contexts. Mechanistically, BNC2-associated phenotypes appear to involve cysteine–histidine zinc-finger-mediated transcriptional regulation, non-coding enhancer activity, epigenetic alterations, RNA-processing-associated nuclear functions, and chromatin-remodeling-dependent control of cell proliferation, differentiation, and stromal activation. This review integrates current evidence on the molecular architecture and regulatory functions of BNC2, critically discusses its context-dependent roles across development and disease, and highlights unresolved questions regarding isoform-specific activity, cell-type-specific regulation, downstream target networks, and clinical translation. A clearer understanding of these mechanisms may support the future evaluation of BNC2 as a biomarker, genetic susceptibility locus, molecular stratification factor, and potential therapeutic regulatory node. Full article

Efficient data processing and signal acquisition are becoming increasingly critical. Pipeline networks present unique topological constraints that complicate the balance between signal sampling efficiency and data-transmission reliability. In this paper, we propose a bi-objective optimization model for the urban pipeline network (UPN). The model optimizes autonomous mobile sensor (AMS) path planning using an Euler path scheme and communication node (CN) deployment using a deterministic deployment scheme. The model aims to minimize both monitoring time (MMT) and data delay (MDD). These two indicators are used as quality of service (QoS) metrics for communication and sensing. By representing the UPN as a graph structure, we establish two mathematical models for the MMT and MDD problems. Then, we introduce a topology-guided heuristic virtual-edge strategy to construct an Euler traversal for the MMT problem. An adaptive simulated annealing (ASA) algorithm is designed to solve the MMT problem. On this basis, the MDD problem is solved using an enhanced ant colony optimization (EACO) algorithm. Simulation results show that the proposed scheme achieves shorter monitoring times and lower data delays. Specifically, the Euler path scheme for the AMS reduces MMT by more than 43.26%, and the deterministic CN-deployment scheme reduces MDD by more than 44.10%. Full article

Equine asthma is a chronic inflammatory disease of the lower respiratory tract, primarily associated with inhalation of organic dust, microbial particles and environmental aeroantigens. Although the inflammatory and immunological mechanisms underlying equine asthma have been extensively investigated, the potential contribution of neuroimmune pathways remains poorly understood. In humans and rodent models, asthma is increasingly recognised as a disorder involving complex bidirectional interactions between the nervous and immune systems. Sensory nerve activation, neuropeptide release, autonomic dysregulation and neuronal remodelling contribute to bronchoconstriction, airway hyperresponsiveness, mucus hypersecretion and chronic airway remodelling. This review summarises current knowledge of the neuroimmune mechanisms involved in asthma, with particular emphasis on comparative aspects across humans, rodents and horses. Literature searches were conducted using the PubMed database, focusing on studies investigating neurogenic inflammation, airway innervation, neuropeptides, transient receptor potential channels and neuronal remodelling in asthma and chronic airway disease. Existing equine evidence indicates the presence of substance P- and calcitonin gene-related peptide-immunoreactive nerve fibres in the equine airways, increased neurokinin-mediated bronchoconstriction in severe equine asthma, and enhanced airway innervation in affected horses. However, compared with human and rodent studies, horse-specific data remain extremely limited. Current evidence suggests that neuroimmune pathways are unlikely to be the primary initiating mechanism of equine asthma, but may act as important modulators of chronic airway dysfunction and disease progression. The marked scarcity of equine studies investigating neuroimmune signalling represents a major knowledge gap and highlights an important direction for future research in equine respiratory medicine. Full article

Spermatogenesis is a highly coordinated biological process in which diploid spermatogonia undergo mitotic expansion, meiotic division, and terminal differentiation into haploid spermatozoa. This process is tightly regulated by intrinsic germ cell programs and extrinsic signals from Sertoli cells within the seminiferous epithelium. Among the signaling pathways governing male germ cell development, all-trans retinoic acid (RA), a bioactive metabolite of vitamin A, has emerged as a master regulator of meiotic initiation and spermatogonial differentiation in mammals. RA functions through nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which regulate transcriptional networks essential for germ cell progression, including the activation of Stimulated by Retinoic Acid 8 (STRA8), a key determinant of meiotic entry. Intratesticular RA homeostasis is maintained by a balance between synthesis via aldehyde dehydrogenase (ALDH) enzymes and degradation by cytochrome P450 family 26 (CYP26) enzymes, ensuring precise temporal and spatial control of germ cell development. While rodent models have defined core mechanisms of RA signaling, the canine testis provides a valuable comparative and translational system due to its physiological similarity to human spermatogenesis and relevance to reproductive management. Recent studies highlight conserved RA signaling pathways in dogs, including receptor-mediated transcriptional regulation, feedback control of RA metabolism, and post-transcriptional modulation via microRNAs. Importantly, pharmacological manipulation of RA signaling can reversibly disrupt spermatogenesis, supporting its potential applications in non-hormonal male contraception. This review integrates molecular, developmental, pharmacological, and comparative evidence and presents RA signaling as a central regulatory axis of spermatogenesis with important translational applications. Full article

Glioblastoma (GBM) is an extremely invasive and incurable tumor. We previously reported predominant ALDH1A3 expression at the invasive front of GBM tumors, which was associated with shorter patient survival, and further showed that ALDH1A3 promoted tumor angiogenesis involving plasminogen activator inhibitor-1 (PAI-1). Here, we investigated whether ALDH1A3 drives cell invasion through retinoic acid (RA) and PAI-1 signaling. Analysis of the TCGA-GBM dataset revealed a positive association between ALDH1A3 and PAI-1 (SERPINE1) expression. Overexpression of ALDH1A3 in GBM cells markedly increased PAI-1 mRNA and protein levels, with cellular colocalization of both proteins, accompanied by robust migration and invasion. These effects were reversed by treatment with a pan-RA receptor (RAR) antagonist AGN193109 (AGN), with a specific PAI-1 inhibitor tiplaxtinin (Tip) or by CRISPR/Cas9-mediated knockout of PAI-1. In a chick chorioallantoic membrane (CAM) model, ALDH1A3-overexpressing cells showed increased invasion, which was reduced by tiplaxtinin (Tip) treatment or PAI-1 knockout. Mechanistically, ChIP-qPCR demonstrated that RA treatment or ALDH1A3 overexpression increased RARα occupancy at the PAI-1 regulatory region, accompanied by increased PAI-1 expression, both of which were diminished by AGN. Collectively, the present study defines an ALDH1A3-RA-PAI-1 signaling axis that contributes to GBM cell motility and invasion. Full article

Commutation failure is likely to occur when an AC fault occurs at the receiving end of an LCC-HVDC system. This threatens transient stability. Conventional commutation failure prevention (CFPREV) control mainly responds to commutation-voltage magnitude variation. However, commutation-voltage phase variation is not fully considered. Its fixed start-up threshold also makes it difficult to adapt to different fault severities. To address these problems, this paper establishes a transient nonlinear large-signal model of the inverter. The model incorporates power angle variation and describes the coupled effects of DC current rise, commutation-voltage drop, and power angle deviation on the extinction angle. Phase-portrait analysis is then used to illustrate the transient evolution and critical characteristics of first commutation failure (FCF). The critical commutation voltage is predicted under different fault severities and further converted into a dynamic CFPREV start-up threshold. Simulations based on the CIGRE LCC-HVDC benchmark model verify the prediction accuracy. They also show that the improved CFPREV strategy suppresses FCF mainly by starting up at an appropriate instant rather than increased compensation strength. Full article

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cell populations with potent immunosuppressive activity. MDSCs accumulate during states of chronic inflammation in response to inflammatory cytokine signaling that triggers emergency myelopoiesis in the bone marrow. In rheumatoid arthritis and experimental models of inflammatory arthritis, MDSCs were initially thought to serve as a regulatory checkpoint that limits excessive inflammation. However, subsequent studies have shown that these cells can either alleviate or worsen arthritis depending on immunophenotype, disease timing, microenvironment, cytokines/chemokines, and transcriptional states. Taken together, the seemingly paradoxical roles of MDSCs in inflammatory arthritis likely reflect a highly plastic and context-dependent myeloid continuum. This review examines current knowledge of MDSCs in inflammatory arthritis, highlighting the conditions that direct their functional diversity and the factors that determine whether they alleviate or exacerbate disease. We also discuss emerging therapeutic strategies and emerging concepts to better understand these immune cell populations in the context of inflammatory arthritis. Full article

Diabetic neuropathy is typically diagnosed with distal sensory and nerve conduction abnormalities. These symptoms may reflect earlier disturbances of axonal maintenance. This review examines axonal transport and cytoskeletal failure as convergent cellular mechanisms of diabetic axonopathy. Long peripheral axons are particularly vulnerable to damage because their integrity depends on continuous communication between the neuronal soma and distal terminals. This process involves the continuous renewal of cytoskeletal and functional proteins and the involvement of organelles such as mitochondria. Diabetes in experimental models disrupts this system at several levels. It slows cargo transport. The supply of neurofilaments, tubulin and retrograde signaling is reduced, and regenerative growth after injury is weakened. Carbonyl stress and AGEs cause modifications of neural proteins, the extracellular matrix, vascular barriers, and the excitability of sensory neurons. RAGE ligands, including AGEs and the proteins HMGB1 and S100, link the diabetic tissue environment to redox and inflammatory signaling. This occurs in neural and glial compartments, as well as in vascular tissue and the immune system. RAGE interacts with DIAPH1 to activate GTPase signaling and remodel the cytoskeleton. The RAGE–DIAPH1 interaction provides a plausible route from diabetic ligand accumulation to cytoskeletal remodeling. These observations provide a mechanistic context for axonal transport, although not all represent direct measurements of cargo movement. Direct evidence for transport impairment comes mainly from experimental studies showing altered slow cytoskeletal transport, impaired retrograde signaling, and weakened regenerative responses. This work highlights the possibility of developing therapies that go beyond symptomatic relief. Verifying the effectiveness of interventions in protecting axonal transport and nerve fiber integrity in diabetic neuropathy may be therapeutically beneficial. Full article

The present investigation evaluated the therapeutic potential of ethanol-derived extracts from Kadsura coccinea root (KCR) against alcohol-induced liver injury (ALI) utilizing a murine experimental system. Male Balb/c mice were administered alcohol intragastrically in a stepwise manner over 8 weeks to establish the ALI model. Experimental outcomes demonstrated that KCR administration substantially improved hepatic functional status, evidenced by marked reductions in circulating hepatic enzymes, specifically aspartate aminotransferase (AST) and alanine aminotransferase (ALT). KCR also increased glutathione (GSH) activity, reduced malondialdehyde (MDA) levels in the liver, and exerted antioxidant effects by boosting the expression of enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase 4 (GPX4). Additionally, metabolomic and transcriptomic analyses identified metabolites and pathways closely linked to oxidative stress, including Glutathione metabolism and the MAPK signaling pathway. Further mechanistic studies revealed that KCR could decrease the phosphorylation of p38, JNK, and ERK, while increasing the expression of Nrf2, HO-1, and NQO1. In conclusion, KCR alleviates ALI by modulating the MAPK/Nrf2 pathway, restoring redox homeostasis, enhancing antioxidant defenses, and improving metabolic disorders. Full article

With the increasing embeddedness of AI robots and other intelligent technologies in organizational workplaces, leader AI-focused attention has emerged as an important reference point for employees as they use and adapt to AI-related technologies. Drawing on work-related rumination theory, this study develops and tests an integrated mediation model to examine how leader AI-focused attention is related to employee proactive behavior through two parallel pathways: problem-solving pondering and affective rumination. It further investigates the moderating role of AI job role clarity. Based on structural equation modeling of multi-wave survey data from 514 employees, the results show that leader AI-focused attention positively predicts employees’ problem-solving pondering and affective rumination. Problem-solving pondering is positively related to employee proactive behavior, whereas affective rumination is negatively related to employee proactive behavior. In addition, AI job role clarity positively moderates the relationship between leader AI-focused attention and problem-solving pondering; specifically, this positive relationship is stronger when employees report higher AI job role clarity. From the perspective of work-related rumination, this study extends the explanation of the psychological mechanisms linking leader AI-focused attention to employee proactive behavior. It also provides theoretical insights and practical implications for understanding the boundary condition of leaders’ attentional signals in AI-related work contexts and for supporting employee proactive behavior. Full article

A comprehensive multiregional characterization of the spectral response of cassava leaves across different ontogenetic stages was performed. For this, ultraviolet (UV), visible (VIS) and shortwave near-infrared (UV-VIS-NIR; 200–900 nm) regions were used to identify spectral signatures and indices for their potential use as biomarkers of leaf development and physiological status of plants under induced senescence conditions. Manihot esculenta Crantz (HMC-1 variety) was used as a model. Spectral signatures were obtained from leaves at two phenological stages (4 and 6 months after planting) using UV-VIS-NIR spectroscopy by the diffuse reflectance technique. Classical and experimental spectral indices were evaluated, and their discriminatory power through different ontogenies was assessed using ANOVA/Kruskal–Wallis and post hoc tests. Senescence effects were further examined by postharvest monitoring (1–20 days), with temporal, ontogenetic, and interaction effects validated using linear mixed models (LMMs), while multivariate structure and spectral convergence were explored via principal component analysis and hierarchical clustering (PCA-HCA). Functionally Enhanced Derivative Spectroscopy (FEDS), comparative analysis, and spectral correlation mapping allowed signal’s selective enhancement and the identification of phenolic compounds, photosynthetic pigments, and structural molecular components. Results showed high ontogenetic stability of UV-associated phenolic signals (~210–220 nm), whereas the VIS region (420–600 nm) clearly differentiated young leaves. The NIR region was stable across ontogeny but highly sensitive to temporal degradation, reflecting changes in water status and internal structure. UV-VIS-NIR indices effectively differentiated young leaves and changes by stress. It is concluded that multiregional characterization of the spectral response supported by FEDS allows the extraction of robust indices with strong potential as biomarkers of leaf maturation and senescence in cassava. Full article