Search Results (4,863)

Heavy metal contamination in mining-affected groundwater may pose potential risks to drinking water safety and human health. In this study, 25 groundwater samples, including 18 from Aquifer IV of the Cenozoic unconsolidated porous aquifer system and 7 from the Taiyuan Formation limestone karst aquifer, were collected from the Zhuxianzhuang Coal Mine, Huaibei Coalfield, China. The Heavy Metal Pollution Index (HPI), Metal Index (MI), Positive Matrix Factorization (PMF), and oral-ingestion health risk model were applied to assess metal contamination, source contributions, and human health risks. HPI values ranged from 8.0 to 37.5, with a mean of 21.5, indicating a low overall pollution level. In contrast, MI values suggested cumulative metal contamination, with higher mean values in Taiyuan Formation limestone karst groundwater (5.60) than in Aquifer IV groundwater (2.38). PMF identified two major factors, interpreted as a natural water–rock interaction source and a combined anthropogenic and mining-related source. Health risks were consistently higher in Taiyuan Formation limestone karst groundwater. Non-carcinogenic risks were higher for children and mainly controlled by As, whereas carcinogenic risks were higher for adults and mainly associated with Cr. These findings highlight the need for aquifer-specific monitoring and source control to reduce toxic metal exposure in coal mining areas. Full article

Nicotinamide adenine dinucleotide (NAD⁺) is a fundamental metabolic cofactor and signaling molecule that supports redox reactions, DNA repair, chromatin regulation, stress adaptation, inflammation, and neuronal maintenance. Age-associated NAD⁺ decline has been implicated in brain aging and neurodegenerative disorders, but the causal node and limiting compartment differ across tissues and disease states. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) catalyzes the final step in NAD⁺ biosynthesis and represents the major nuclear isoform of the mammalian NMNAT family. Direct human genetic evidence establishes NMNAT-1 as a causal gene in inherited retinal degeneration, whereas evidence linking endogenous NMNAT-1 to broader brain aging or sporadic neurodegeneration is mainly convergent preclinical, preliminary, or indirect. Beyond NAD⁺ synthesis, biochemical and Drosophila studies suggest possible chaperone-like and proteostasis-supporting functions, but a separable NAD⁺-independent function of endogenous mammalian NMNAT-1 has not yet been established in vivo. Here, we review the molecular structure, localization, and regulation of NMNAT-1, emphasizing calibrated distinctions among catalytic nuclear NAD⁺ supply, engineered axonal protection, pathway-adjacent NAD⁺ interventions, and putative non-catalytic protection. We further discuss how NMNAT-1 dysfunction may contribute to aging-associated genomic instability, neuroinflammation, synaptic impairment, retinal degeneration, selected neurodegenerative models, and glioma biology. Finally, we evaluate therapeutic strategies targeting NMNAT-1 and NAD⁺ pathways, noting that no human trial has yet established efficacy for an NMNAT-1-directed neurological therapy. A compartment-aware and evidence-stratified view is therefore essential for translating NMNAT-1 biology into interventions for age-related neural disease. Full article

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. Smoking is the primary etiological factor, but growing evidence suggests the involvement of estrogen in its development and progression, although its role remains unclear. This study explores: (i) the effects induced by estrogen, namely, 17β-estradiol (E2), alone or in combination with a mixture of inflammatory cytokines (Mix), in two human NSCLC cell lines, A549 and Calu1, and (ii) whether and how tumor cells can modulate the activation of normal lung fibroblasts. We found that E2 significantly enhances migration, invasion, and epithelial–mesenchymal transition in NSCLC cells, as well as their resistance to cisplatin, particularly in combination with Mix. Pharmacological inhibition of ERβ reversed the E2-induced effects, implicating ERβ in E2-mediated signaling. Furthermore, E2 increased autophagic flux and induced a shift toward secretory autophagy and the release of extracellular vesicles, which activated normal lung fibroblasts, as demonstrated by the increased expression of α-SMA, FAP, PDGFR-β, and PDPN. The clinical relevance of these data was supported by computational analyses revealing an elevated expression of the Mix gene signature, including TGF-β, IL-6, IL-8, CCXL-16, and ERβ, which was associated with shorter overall survival in NSCLC patients. This molecular profile was linked to the elevated expression of secretory autophagy genes and cancer-associated fibroblast markers. Validation in three large clinical cohorts (TCGA-LUNG, OAK and POPLAR) strengthens the clinical relevance of this E2-related pro-tumor axis while suggesting a promising therapeutic avenue for NSCLC patients. Full article

The article reflects on the care for the work of creation within Benedictine spirituality and within the broader tradition of the Cistercian Order. It seeks to demonstrate that monastic spirituality, though developed in a pre-modern context, contains enduring theological and ethical intuitions that remain relevant for contemporary ecological reflection. The starting point of the analysis is the Rule of Saint Benedict written by Benedict of Nursia, which, although it does not employ the modern vocabulary of ecology or environmental ethics, nevertheless articulates a coherent vision of human life characterized by reverence, moderation, and responsibility toward the created world. Particular attention is given to key spiritual and anthropological dimensions of the Benedictine tradition, such as attentive listening (obsculta), humility, moderation, stability, and responsible work, expressed synthetically in the principle ora et labora. These elements are interpreted not only as monastic disciplines shaping individual and communal life, but also as forming a relational anthropology in which the human person is understood as fundamentally embedded within a network of relationships with God, other people, and creation. In this sense, Benedictine spirituality already implies a non-exploitative attitude toward the natural world. The article then examines how concern for creation has been deepened and concretized in the spirituality, institutional practice, and historical development of the Cistercian Order. Drawing on selected Cistercian documents as well as contemporary monastic reflections, the study shows that care for the natural environment is inseparably linked with spiritual attentiveness to God, interior silence, openness of heart, and readiness to serve. The Cistercian tradition, with its emphasis on simplicity of life, manual labor, and harmonious integration with the surrounding environment, develops these Benedictine intuitions in a particularly concrete and historically embodied form. From this perspective, a pro-ecological attitude is not interpreted merely as a reactive response to contemporary environmental crises, but rather as a structural consequence of a theologically grounded vision of reality. It emerges from a deep relationship with God as Creator and from a sense of entrusted responsibility for creation understood as a gift rather than as an object of domination. Ecological sensitivity is thus presented as an intrinsic dimension of monastic spirituality rather than an external adaptation to modern concerns. The main research question of the article is: to what extent and in what way do Benedictine and Cistercian spiritual traditions provide theological, anthropological, and ethical foundations for an ecological attitude toward creation within the framework of contemporary integral ecology. To address this problem, the study employs qualitative research methods grounded in theological inquiry. The primary method is textual analysis of the Rule of Saint Benedict and selected Cistercian documents, complemented by theological–hermeneutical interpretation aimed at identifying key spiritual principles and their implicit ecological implications. In addition, the study applies a historical–critical perspective in order to situate monastic sources within their original cultural and theological context, as well as a comparative theological approach, which enables a dialogue between classical monastic spirituality and contemporary ecological theology. These methods are used not only to reconstruct historical meanings, but also to interpret monastic texts in light of contemporary debates on integral ecology, sustainability, and the ethics of responsibility for our common home. In this way, the article highlights a significant continuity between monastic wisdom and modern ecological reflection, showing their mutual capacity for enrichment. Full article

Mechanical stress is thought to be involved in the pathogenesis and pathophysiology of osteoarthritis (OA). However, much remains to be elucidated regarding how chondrocytes sense and respond to mechanical stress (stress sensing and response factors). Additionally, it still remains unclear whether there are defensive responses and mechanisms to protect against pathological agents and mechanical stress in articular cartilage tissue. This study was designed to determine whether repetitive mechanical force, at physiologic levels, affects the expression of factors regulating autophagy such as the autophagy-related proteins ATG5, Beclin-1, and Parkin, and the autophagy process as well as cellular activity in cultured chondrocytes. Three-dimensional cultured tissue was generated from human chondrocytes using a collagen sponge scaffold. After physiological mechanical loading of the 3D cell–collagen sponge construct, comparative analyses of expression levels of ATG5, Beclin-1, and Parkin were performed in human chondrocytes. Chondrocyte activity and Transmission Electron Microscopy (TEM) analysis for detecting autophagy process were also analyzed with or without repetitive compressive loading. In chondrocytes, 60 min or 180 min repetitive compressive loading significantly decreased the expression of ATG5, Beclin-1 and Parkin in comparison with the non-loading group. TEM analysis indicated that, in normal chondrocytes of the non-loading group, the autophagy process was shown to be progressing. In contrast, repetitive loading decreased the number of autophagosomes and autolysosomes in chondrocytes. In addition, numerous degenerated organelles that had not undergone autophagy were observed within the chondrocytes under repetitive loading. The ATG5 and Beclin-1 proteins are known to play crucial roles in regulating cellular autophagy. Furthermore, repetitive mechanical loading caused a decreased expression of Parkin, a mitophagy regulator in chondrocytes. Our results indicate for the first time that a decrease in mitophagy, as well as cellular autophagy, in response to mechanical stress, even at the physiologic level, leads to the accumulation of defective mitochondria and abnormal cellular proteins, resulting in reduced chondrocyte activity and affecting the maintenance of cartilage tissue homeostasis, ultimately contributing to the progression of OA. Full article

Despite growing regulatory and investor attention to human capital as a core pillar of corporate sustainability and ESG reporting, it remains unclear how human capital-related information is priced in financial markets. This study examines the associations between human capital disclosure, management practices, and firms’ financing costs. Using a global panel of 1180 non-financial firms across 53 countries from 2017 to 2023, we employ Bloomberg ESG data to construct measures of human capital disclosure, management practices, and materiality. Panel regression analyses indicate that while human capital management practices exhibit no significant standalone associations, human capital disclosure is positively associated with the cost of equity, cost of debt, and the weighted average cost of capital. However, we document a significant complementary effect: when coupled with strong management practices, disclosure is associated with a lower cost of equity, particularly in contexts where human capital is financially material. Furthermore, the positive association between disclosure and capital costs becomes weaker as human capital materiality increases. Overall, our findings suggest that capital markets do not uniformly price human capital information; rather, its valuation is highly conditional, depending on the substantive credibility of management practices and contextual materiality. Full article

Non-human animals are systematically excluded from public narratives, rarely recognized as sentient subjects, and instead framed within anthropocentric narratives of production and consumption; efforts to challenge this pattern and make the more-than-human world visible often encounter editorial resistance and structural constraints. This study examines how anti-speciesist journalists in Spanish written media navigate such resistance to make non-human animals legitimate subjects of news. Drawing on semi-structured interviews with nine self-identified anti-speciesist journalists, analysed through reflexive thematic analysis, the study identifies strategies organized across four non-mutually exclusive categories, namely, discursive, relational, framing, and structural, ranging from self-censorship and strategic language use to coalition-building and the creation of independent platforms. Findings reveal a key distinction between visibility strategies, which succeed in securing publication, and root-level strategies, which challenge the carnist and anthropocentric assumptions structuring newsworthiness itself. These practices reveal the pragmatism, creativity, and resilience of journalists working under structural, ideological, and normative constraints, while also highlighting the limits of anti-speciesist reporting within mainstream media. The study contributes to Critical Animal Media Studies, environmental communication, and journalism research by illuminating the intersection of ethical advocacy, professional strategy, and counter-hegemonic practice and offers recommendations for expanding coverage of the more-than-human world across ideological, editorial, and structural divides. Full article

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection and the primary etiological agent of cervical cancer. Despite the high global disease burden, the Middle East and North Africa (MENA) region faces substantial challenges in HPV prevention and control. This narrative review aimed to synthesize existing evidence on the prevalence, genotypic distribution, awareness, vaccination status, clinical outcomes, and the role of HPV in non-cervical malignancies in the MENA region. Methods: PubMed, Web of Science, Scopus, and Google Scholar were searched, and 122 studies were included. Findings were synthesized qualitatively and descriptively. Cohort studies, systematic reviews, and meta-analyses were prioritized to support inferences about associations and potential causal relationships. Results: HPV prevalence in the general female population of the MENA region ranged from 4.7% to 53.3%, exceeding 90% in high-risk groups and patients with malignancies. The most common genotypes were HPV16 and HPV18; however, distribution patterns varied across populations. Key risk factors included younger age, multiple sexual partners, early age at first sexual intercourse, smoking, and alcohol consumption. General awareness was low to moderate, and vaccination coverage was very low in most countries. Barriers included lack of knowledge, fear of side effects, religious concerns, and social stigma. Evidence also indicates an association between HPV and non-cervical malignancies (head and neck, esophageal, gastric, breast, and thyroid cancers), with HPV DNA detected in tumor tissues. Conclusions: HPV poses a significant public health challenge in the MENA region, characterized by high prevalence, genotypic diversity, limited knowledge and awareness, and unsatisfactory vaccination coverage. Expanding screening and vaccination through financial support, culturally and religiously appropriate education, and longitudinal studies to monitor genotypic changes and associations with other malignancies are essential measures to reduce the burden of HPV-related diseases in the region. Full article

Skeletal disorders, including osteoporosis, osteoarthritis, rheumatoid arthritis, and osteonecrosis of the femoral head, are common chronic conditions that substantially affect health and quality of life. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has increasingly been implicated in abnormal bone remodeling, cartilage degeneration, synovial pathology, and impaired skeletal homeostasis. Aerobic exercise is an important non-pharmacological approach for maintaining skeletal health, but the role of ferroptosis in its protective effects remains incompletely understood. Previous reviews have mainly discussed ferroptosis in skeletal disorders or the beneficial effects of exercise on skeletal health as separate topics. In contrast, this review places aerobic exercise, ferroptosis, and skeletal disorders within a unified framework and summarizes current evidence across osteoporosis, osteoarthritis, rheumatoid arthritis, and osteonecrosis of the femoral head. We further discuss how aerobic exercise may influence ferroptosis through the regulation of iron homeostasis, lipid peroxidation, antioxidant defense, and inflammatory responses, with attention to recently emerging molecular evidence and to the distinction between direct findings from bone- and joint-related tissues and supportive evidence from non-skeletal systems. Current direct evidence is concentrated mainly in osteoblast-related bone loss and osteoarthritis and is derived predominantly from animal and cellular studies, whereas direct clinical evidence in humans remains limited. Overall, available evidence supports ferroptosis as a potential mechanistic link between aerobic exercise and skeletal protection, but its role in mediating exercise-induced benefits in humans has yet to be established. Further clinical validation of this relationship may help clarify the biological basis of aerobic exercise interventions and support the development of more targeted exercise strategies for the prevention and management of skeletal disorders. Full article

Industrialization and mining raise the heavy metal burden of soil ecosystems and create risks for both the environment and human health. Apportionment becomes difficult when neighboring facilities emit overlapping metal signatures, and conventional receptor models compound the difficulty by returning contribution shares without an attached uncertainty statement. This study develops a probabilistic apportionment framework for the coal–steel industrial zone of Zonguldak, Turkey, using 93 georeferenced topsoil stations and eight priority metals. Graphical Lasso estimates a sparse conditional dependency graph whose nodes are the measured metals; fixed propagation over that graph expands each observation into a 24-dimensional relational representation; and a Dirichlet neural posterior estimator maps the representation to source contribution distributions. The Dirichlet parameterization enforces non-negativity and unit sum by construction and delivers 95% credible intervals at every station; empirical coverage on held-out simulations was 0.957 against a nominal 0.95. Averaged across the province, posterior mean contributions were 0.25 for the iron-and-steel sector, 0.25 for thermal power generation, and 0.50 for a composite residual class that combines geogenic background with unmodelled anthropogenic inputs. The two industrial signals concentrate around Ereğli and Çatalağzı, while the residual class dominates elsewhere. The graph employed here encodes chemical relationships among metals and not geographical relationships among stations; maps of the posterior estimates are reported as post hoc visualizations. The framework is offered as an uncertainty-aware methodological contribution, and comparison against established receptor models remains to be carried out. Full article

Automated license plate readers (ALPRs) are often evaluated as discrete police tools, although their public power arises from cross-vendor socio-technical infrastructure. This article examines roadside and mobile sensors, vehicle-attribute classification, cloud archives, commercial databases, real-time crime center integration, interagency access, automated alerts, and police action. Flock Safety supplies the principal documentary case because unusually extensive public records permit system-level tracing; Axon/Fusus, Motorola Vigilant/VehicleManager, and federal access to commercial ALPR data establish the wider vendor-independent boundary. A structured documentary analysis of 59 sources triangulates official records, peer-reviewed research, vendor materials used only for stated functions, and record-based investigations. It integrates boundary critique, control-structure mapping, feedback analysis, constitutional doctrine, a STRIDE-informed threat model, and empirical research on policing effectiveness and surveillance effects through 3 August 2026. The analysis identifies four conditional mechanisms: infrastructure aggregation, authority diffusion, asymmetric feedback, and rights invisibility. The article reformulates the Rights Control Deficit (RCD) as a non-arithmetic profile relation between operational demands and effective governance capacity and applies it to three documented configurations and a clearly labeled normative benchmark. Seven falsifiable propositions specify variables, indicators, suitable methods, and disconfirming conditions for later empirical study. A rights-preserving hybrid-intelligence architecture combines bounded automation with judicial authorization, short retention, sensitive-location protections, immutable audit, availability safeguards, independent review, contestability, sanctions, and credible termination authority. The evidence identifies capabilities, activated pathways, and conditional risks; it does not estimate population prevalence or a universal ALPR-specific causal effect. Meaningful human oversight is an institutional control property, not merely an officer’s presence at an interface. Full article

Forensic genetics is moving from locus-based DNA profiling toward genome-wide inference enabled by high-density single-nucleotide polymorphism (SNP) data. While short tandem repeats remain central to routine human identification, SNP-based technologies and massively parallel sequencing have expanded the analysis of distant kinship through detection of identity-by-descent (IBD) segments and shared autosomal DNA. This narrative review synthesizes the biological basis of SNP-based distant kinship inference, the statistical and computational frameworks used to model genomic relatedness, and the operational transition from relatedness detection to forensic genetic genealogy (FGG). It distinguishes genetic genealogy database matching from formal forensic kinship testing, targeted SNP panels, SNP capture, low-coverage sequencing, Bayesian and machine-learning approaches, and independent forensic confirmation. Applications in criminal investigations, unidentified human remains, historical identifications, and broader relationship-inference contexts are discussed. The review also examines limitations related to recombination, stochastic inheritance, marker density, genotype quality, degraded or mixed forensic samples, population structure, endogamy, database composition, and genealogical record availability. Ethical and regulatory issues involving consent, privacy, database governance, law-enforcement access, data retention, and non-consenting relatives are considered. Overall, SNP-based forensic genomics can generate powerful investigative leads, but its outputs must be interpreted within method-specific analytical and evidentiary boundaries. Full article

Background: Parkinson’s disease (PD) exhibits remarkable clinical heterogeneity, with substantial variability in motor progression, cognitive decline, and the development of non-motor manifestations. Although the propagation of pathological alpha-synuclein is considered a central mechanism of PD pathogenesis, it does not fully explain why specific neuronal populations demonstrate differential susceptibility to degeneration. Emerging evidence suggests that selective neuronal vulnerability is determined by the interaction of multiple biological domains, including calcium homeostasis, mitochondrial bioenergetic capacity, lysosomal function, axonal architecture, synaptic resilience, and neuroinflammatory responses. Methods: A structured critical narrative review was performed using PubMed/MEDLINE, Scopus, and Web of Science databases from inception to March 2025. Only full-text articles published in English and peer-reviewed journals were included. Evidence from human post-mortem studies, genetic analyses, biomarker investigations, experimental models, induced pluripotent stem cell studies, and longitudinal clinical cohorts were systematically synthesised to identify the principal mechanisms underlying selective neuronal vulnerability and their potential translational application. To capture evidence published after this electronic cut-off, a supplementary manual review of reference lists of key systematic reviews and landmark publications was conducted up to the date of manuscript submission; references with 2025 or 2026 publication dates entered through this supplementary process. The supplementary manual review was conducted as a targeted scan of reference lists of key systematic reviews and high-impact publications identified during the primary search and did not constitute an independent updated systematic search. Results: Five interconnected biological domains emerged as key determinants of neuronal susceptibility in PD: calcium-mediated metabolic stress associated with autonomous pacemaker activity, mitochondrial dysfunction and energetic failure, impaired lysosomal degradation and proteostasis (particularly involving the GBA1–glucocerebrosidase pathway), vulnerability related to extensive axonal and synaptic architecture, and neuroinflammatory mechanisms involving microglial and astrocytic activation. Among these domains, the lysosomal pathway currently provides the strongest translational link between molecular mechanisms and measurable clinical outcomes. Based on this integrated framework, we propose the Parkinson’s Vulnerability Index (PVI), a hypothesis-generating multidimensional model combining genetic, enzymatic, alpha-synuclein seeding, cognitive, olfactory, and neuroimaging biomarkers to facilitate biological stratification and improve the design of mechanism-targeted clinical trials. Conclusions: Selective neuronal vulnerability provides a complementary framework to alpha-synuclein propagation models for understanding the heterogeneity of PD. The proposed PVI is not intended as a diagnostic or prognostic clinical instrument but as a research tool requiring prospective validation. Future precision medicine approaches in PD may benefit from integrating vulnerability-related biomarkers with existing biological staging systems to identify patients most likely to benefit from targeted disease-modifying therapies. Full article

Interest in sustainable protein sources is increasing because of environmental concerns related to animal agriculture and the growing burden of chronic non-communicable diseases. Plant-derived bioactive peptides (PDBAPs), amino acid sequences released from dietary proteins, are gaining attention because experimental studies have reported activities relevant to hypertension, type 2 diabetes, and cancer-associated processes. Although animal proteins have long been major sources of bioactive peptides, plant materials may offer advantages such as abundance, potentially lower production costs, and broad cultural acceptability; however, these benefits depend on the source, processing requirements, safety, and scale-up conditions. This review integrates plant sources, processing technologies, proposed mechanisms of action, and translational barriers. Current research covers traditional sources, including legumes and cereals, as well as agro-industrial by-products such as potato peels, spent coffee grounds, and broccoli stems. Modern processing strategies increasingly combine enzymatic hydrolysis or microbial fermentation with process-assisting technologies, including ultrasound treatment and subcritical water processing, to improve protein recovery or peptide release. Recent studies also examine proposed mechanisms of PDBAP activity, including Keap1/Nrf2-associated responses and inhibition of enzymes involved in metabolic disorders. Evidence is interpreted according to the stage of experimental validation, from computational prediction and cell-free assays to cellular, animal, and human studies. Key challenges remain, particularly digestive instability, uncertain systemic bioavailability, bitterness, safety standardization, and limited human clinical evidence. Future work should prioritize standardized extraction and analytical methods, optimized delivery systems, and robust clinical trials. Full article

Tuberculosis (TB) remains a global health problem, and attention is focused on host immunometabolic pathways influencing antimicrobial immunity, tissue injury, and treatment response. This comprehensive review integrates evidence on the kynurenine pathway (KP) of tryptophan (TRP) metabolism in TB and evaluates its potential as a host-directed therapeutic target. Evidence from human cohorts, in vitro systems, animal models, and non-human primates indicates that Mycobacterium tuberculosis activates the KP across myeloid, antigen-presenting, non-hematopoietic lung, granulomatous, pleural, and central nervous system compartments. KP activation is shaped by interferon-γ signaling, mycobacterial burden, infection duration, strain virulence, and host regulatory mechanisms. Increased indoleamine 2,3-dioxygenase-related (IDO) activity, TRP depletion, kynurenine accumulation, and kynurenine–aryl hydrocarbon receptor (AhR) signaling are associated with impaired T-cell proliferation and recruitment, suppressive myeloid phenotypes, and spatially restricted immunoregulatory niches within granulomas. Accumulated data indicate context-dependent protective effects of the KP manipulations, through restriction of excessive inflammation. Furthermore, the KP-related changes may have biomarker value. Integrated assessment of enzyme expression, kynurenine-to-tryptophan ratio (K/T ratio), downstream metabolites, and signaling pathways will be essential for translational studies. Future studies should therefore evaluate KP activity using integrated readouts, including IDO expression, metabolites and their ratios, and KYN–AhR signaling, and should determine whether context-specific pathway modulation can safely improve outcomes when combined with conventional anti-TB therapy. Full article