Search Results (516)

Human airways maintain homeostasis through intricate cellular interactomes combining secretome-mediated signalling and mechanotransduction feedback loops. This review presents the first unified map of bidirectional mechanobiology–secretome interactions between airway epithelial cells (AECs), smooth muscle cells (ASMCs), and chondrocytes. We unify a novel three-component regulatory architecture: epithelium functioning as environmental activators, smooth muscle as mechanical actuators, and cartilage as calcium-dependent regulators. Critical mechanotransduction pathways, particularly YAP/TAZ signalling and TRPV4 channels, directly couple matrix stiffness to cytokine release, creating a closed-loop feedback system. During development, ASM-driven FGF-10 signalling and peristaltic contractions orchestrate cartilage formation and epithelial differentiation through mechanically guided morphogenesis. In disease states, these homeostatic circuits become pathologically dysregulated; asthma and COPD exhibit feed-forward stiffness traps where increased matrix rigidity triggers YAP/TAZ-mediated hypercontractility, perpetuating further remodelling. Aberrant mechanotransduction drives smooth muscle hyperplasia, cartilage degradation, and epithelial dysfunction through sustained inflammatory cascades. This system-level understanding of airway cellular networks provides mechanistic frameworks for targeted therapeutic interventions and tissue engineering strategies that incorporate essential mechanobiological signalling requirements. Full article

To address the premature corrosion failure of chromium-based coatings in harsh environments (e.g., high temperatures, chloride-containing solutions), this work systematically investigates how rare-earth (RE, i.e., Ce and La) elements regulate nitrogen (N) adsorption and diffusion behavior in Cr during the early stages of nitriding, a critical corrosion protection strategy, using first-principles density functional theory (DFT). Results show that RE preferentially occupies Cr substitutional site, increasing the Young’s modulus from 293.5 GPa (pristine Cr) to 344.9 GPa (Ce-doped) and 348.7 GPa (La-doped). Surface RE doping on Cr(110) significantly enhances N adsorption energy from −3.23 eV to −3.559/−3.645 eV (Ce-/La-doped), whereas subsurface doping slightly weakens the adsorption. Moreover, the energy barrier for N penetration into subsurface is reduced from 2.11 eV to 2.03/1.91 eV (Ce-/La-doped), thereby facilitating nitridation. Notably, RE is found to strongly trap vacancies and N atoms, leading to increased migration barriers and thus hindering their long-range transport. These findings demonstrate that RE exhibits a dual role during nitriding: promoting N incorporation at the surface while restricting its deep diffusion into the bulk. The study provides theoretical insights into the atomistic mechanisms by which RE elements modulate nitriding efficiency in Cr-based alloys, offering guidance for the design of RE-doped surface-modified coatings with improved corrosion resistance. Full article

Neutrophils are the most abundant circulating leukocytes and essential components of innate immunity. Through mechanisms such as phagocytosis, reactive oxygen species (ROS) production, degranulation, and neutrophil extracellular trap (NET) formation, they play a crucial role in host defense. However, dysregulated neutrophil responses are linked to chronic inflammatory conditions, including periodontitis. This review summarizes current evidence on neutrophil biology in periodontal health and disease, focusing on functional mechanisms, recruitment pathways, the influence of dysbiosis, and their potential as biomarkers and therapeutic targets. Neutrophils display a dual role in periodontal tissues: while protecting against microbial invasion, their excessive or impaired activity contributes to tissue destruction. Altered chemotaxis, defective phagocytosis, and uncontrolled NET release perpetuate inflammation and alveolar bone loss. Neutrophil-derived enzymes, including myeloperoxidase, elastase, and matrix metalloproteinases, emerge as promising biomarkers for early diagnosis. In parallel, therapeutic strategies targeting oxidative stress, NET regulation, or neutrophil hyperactivity are being explored to preserve periodontal tissues. Neutrophils are central players in periodontal pathophysiology. Understanding their regulation and interaction with the oral microbiome may enable the development of novel diagnostic and therapeutic approaches, ultimately improving periodontal disease management. Full article

This study investigates the determinants of household borrowing choices in Thailand, with a focus on the risks associated with formal and informal credit markets. Using cross-sectional survey data from 6949 respondents across 77 provinces collected in September 2021, we employ multinomial regression models to analyze how demographic, occupational, and income factors shape debt outcomes. The results indicate that younger and lower-income individuals in Bangkok are more likely to remain debt-free, while older, higher-income, and farming households are strongly associated with formal borrowing. In contrast, unemployed individuals, retirees, business owners, and freelancers disproportionately rely on informal credit channels, exposing them to high interest rates, repayment difficulties, and heightened financial risk. Regional disparities further underscore structural inequalities: households in the north and northeast are more likely to access formal finance, whereas those in Bangkok and the south tend to turn to informal lenders. These findings highlight the risks of financial exclusion and the persistence of informal lending in emerging economies. Policy measures that expand access to regulated credit, promote microfinance, and strengthen consumer protection frameworks are essential to mitigate household financial vulnerability and reduce exposure to debt traps. Full article

Cancer survivors (CS) constitute an expanding population with underrecognized cardiometabolic risk. Despite substantial improvements in five-year survival rates, both childhood and adult survivors remain at high risk for premature morbidity and mortality. These risks are particularly pronounced following exposure to anthracyclines and/or chest radiotherapy, typically in a dose-dependent manner. In Chile, the establishment of the National Pediatric Antineoplastic Drug Program (PINDA) in 1998 marked a milestone in improving equitable access to high-quality pediatric oncology care through evidence-based treatment protocols across the public health system; the adult counterpart (PANDA) has developed diagnostic, treatment, and monitoring protocols for hematological neoplasms. Few prospective cohort or mechanistic studies have clarified risk stratification or surveillance strategies in survivor populations. The regulated, short-term activation of inflammation and innate immunity can be an adaptive and protective response to tissue injury, whereas persistent low-grade inflammation may trigger neutrophil extracellular traps formation (NETosis) and other maladaptive pathways that accelerate endothelial injury, thrombosis, and adverse cardiovascular remodeling. NETosis represents a putative immunomodulatory target for therapeutic immunomodulation in heart failure and maladaptive left ventricular remodeling in preclinical models. Concurrently, skeletal muscle-derived and hormonal mediators known as exerkines—together with increased NET activity—may modulate the pathophysiology of chronic cardiometabolic disease and contribute to cancer progression, particularly in the context of obesity, diabetes, and insulin resistance. Structured exercise is a promising non-pharmacological intervention that modulates inflammatory and metabolic pathways and may thereby help prevent non-communicable diseases, including cancer. We synthesize basic and clinical evidence to (1) define how cancer therapies promote low-grade inflammation and NETosis; (2) describe how exerkines and structured exercise influence cardiometabolic biology; and (3) evaluate exercise as a mechanistic and clinically pragmatic strategy to reduce long-term CVD risk in pediatric and adult CS. Full article

Outdoor thermal comfort is a critical determinant of urban livability and public health, particularly in the face of the increasing frequency and intensity of extreme weather events. While meteorological variables are well-established drivers of thermal stress, the influence of ambient air pollution on human thermal perception remains poorly understood and largely overlooked in urban climate research. To address this gap, this study investigates the multidimensional effects of six major air pollutants PM_2.5, PM₁₀, SO₂, NO₂, O₃, and CO on the Universal Thermal Climate Index (UTCI) across 370 Chinese cities from 2020 to 2024. Using integrated spatiotemporal analysis, we found significant seasonal, diurnal, and climatic heterogeneity in pollutant–UTCI interactions. Our findings reveal that O₃ and PM₁₀ amplify thermal stress during summer daytime through photochemical heating and radiative forcing, whereas PM_2.5 and CO reduce nocturnal heat loss in winter by trapping long-wave radiation, effectively acting as thermal insulators. These effects are further modulated by local climate: arid regions (e.g., Lanzhou) experience exacerbated O₃-driven heat stress, while cold zones (e.g., Harbin) benefit from particulate-induced warming in winter. Meteorological factors serve as dual regulators; temperature and solar radiation directly elevate the UTCI, while wind and humidity govern pollutant dispersion and thus indirectly shape thermal comfort. This study not only advances the scientific understanding of air pollution’s role in urban thermal environments but also provides actionable, data-driven insights for climate-resilient urban planning, public health interventions, and integrated environmental policies that jointly address air quality and thermal comfort in rapidly urbanizing regions. Full article

Background: Bone metastasis of breast cancer (BC) is a key reason for poor prognosis. Recently, natural ingredients derived from plants have been found to exert a broad anti-tumor effect and are considered to be promising candidates for adjuvant therapy. Astragalin (AS) was found to inhibit the progression of several types of tumors; however, the role of AS in regulating the bone metastasis of BC is still unclear. Methods: The effects of AS on the progression of bone metastasis of BC were detected in vivo through safranin O and fast green staining, in vivo living imaging and microCT. The BrdU assay and Annexin V-PI analysis were used to detect the effects of AS on the growth of BC cells. Furthermore, TRAP staining was performed to examine the formation of osteoclasts regulated by AS. A transcriptome was performed to explore the downstream effects of AS on regulating the growth of BC cells, and the mechanism was further confirmed by Western blot and real-time PCR. Results: Administration of AS could effectively attenuate the bone destruction and the progression of bone metastasis of BC. The growth of BC cells can be inhibited by AS by inducing ER stress-mediated upregulation of Ddit3. In addition, AS can also prevent osteoclastogenesis through inhibiting the activation of the AKT pathway. Conclusions: Our studies suggest that AS could be an ideal adjuvant therapy for attenuating the progression of bone metastasis of BC, since it can directly restrict the growth of tumor, as well as attenuate osteolysis. Full article

Background/Objectives: Osteoporosis is caused by excessive osteoclast activation via the receptor activator nuclear factor kappa B ligand (RANKL), which is released from osteoblasts or osteocytes. RANKL regulates osteoclast activity by binding to the receptor activator of nuclear factor kappa B (RANK) in the canonical pathway or leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) in the non-canonical pathway. In this study, we attempted to develop an intact small-fragment protein based on RANKL by removing the RANK-binding site and transforming the amino acid residues at crucial sites to inhibit osteoclast activity and treat osteoporosis. Methods: We expressed a small-fragment variant of RANKL as a soluble glutathione S-transferase (GST) or 6x histidine (His)-tagged fusion protein using a GST- or His-binding domain tag expression vector system. To generate an intact form of small-fragment RANKL, ribosome-inactivating protein–His-fusion RANKL was purified using HisTrap affinity chromatography and treated with tobacco etch virus nuclear inclusion endopeptidase to remove the His-tag fusion protein. Tartrate-resistant acid phosphatase (TRAP) and bone resorption pit formation assays were performed to analyze the inhibitory effects on osteoclast differentiation and activation. Results: The intact forms of 225RANKL295P and 225RANKL295A showed the strongest inhibitory effects on TRAP activity and bone resorption pit formation. Conclusions: Using an optimal construct design, a large and diverse range of small RANKL fragments could be generated. This suggests that the generation of small-fragment RANKL provides a promising avenue for the advancement of novel therapeutic approaches to osteoporosis. Full article

Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a critical pathogenic mechanism and a highly promising therapeutic target in sensorineural hearing loss (SNHL). The irreversible loss of auditory hair cells, the hallmark of SNHL, creates an urgent need for novel therapeutic strategies. This review provides a translational perspective on ferroptosis, connecting its core molecular machinery to tangible opportunities for otoprotection. We systematically analyze three key targetable nodes: the iron metabolic pathways that fuel the process; the lipid peroxidation machinery that executes membrane damage; and the collapse of the System Xc⁻–GSH–GPX4 antioxidant axis. By framing the disease mechanism through these actionable targets, we highlight a clear rationale for developing new hearing preservation therapies. We conclude by surveying the most promising pharmacological approaches, including iron chelators, radical-trapping antioxidants, and bioactive natural products, offering a strategic roadmap for future drug discovery in audiology. Full article

The nematode-trapping fungus (NTF) Arthrobotrys oligospora (A. oligospora) is a promising biocontrol agent, but the transcriptional regulators governing its predation remain poorly understood. Here, we demonstrated that the APSES transcription factor AoMbp1 is a master regulator of its development and stress adaptation. Deletion of AoMbp1 severely impaired mycelial growth, conidiation, trap formation, and tolerance to oxidative and osmotic stresses. Transcriptome analysis revealed that these defects were associated with the widespread downregulation of genes, including those within the MAPK signaling pathway. Crucially, we showed that AoMbp1 directly binds to the promoter of AoSho1, a key upstream sensor of the MAPK cascade, and activates its expression. This finding establishes a direct AoMbp1-AoSho1 regulatory axis controlling trap morphogenesis and environmental adaptation. Our study provides novel mechanistic insights into the regulation of nematode trapping and identifies a potential target for enhancing the efficacy of A. oligospora as a biocontrol agent. Full article

Utilization of solid waste as building material (USB) is a promising strategy that effectively addresses the challenges of safety and environmental pollution posed by solid waste and alleviates the scarcity of natural resources to facilitate the sustainable production of building materials. However, USB implementation and promotion have not yet matured in China because of various barriers. Therefore, this study employed the GT-DEMATEL-ISM-MACMIC model to identify the critical factors in USB implementation and examine the interactions and relationships among barriers to propose targeted recommendations. The results identified 33 barriers and revealed a distinct causal hierarchy. It was found that the macro-level barriers at the apex of the hierarchy, ‘incomplete policies and legislation’, ‘poor supervision and regulation of solid waste’, and ‘insufficient financial subsidies and incentives’, are critical barriers to USB implementation. A key outcome of this study is the identification of the most critical and obstinate barrier path evolution in USB implementation, where incomplete policies and regulations (P1, P2) lead to underdeveloped markets and capital (M6, E2), as well as low stakeholder motivation (S4), which in turn, exacerbates policy inertia and traps USB development in a state of deadlock. Conversely, detail-level barriers at the technical and managerial levels, such as ‘limited innovation in management models’ and ‘single type and limited application of renewable building material’, tend to be less influential than other barriers. Therefore, USB promotion can be achieved by strengthening policies and legislation, improving policy systems, and increasing financial subsidies. The results of this study will assist China and other developing countries in identifying critical barriers to USB implementation, offer practical approaches for promoting USB implementation, and provide methodological guidance for similar studies. Full article

Historically, predator control has been a frequent practice conducted in the hunting grounds of Spain. After the approval of Law 42/2007 on Natural Heritage and Biodiversity, and the enforcement of international regulations, predator control methods are required to be selective, non-massive, and conducted by trained specialists when traps are used; however, there is a lack of research on the current status of predator management. Data was gathered from 16 regional wildlife departments and from 373 questionnaires from hunting grounds targeting the conservation of small game species. Seven predatory species were included in the regional game species lists, the most frequently controlled being the red fox (Vulpes vulpes, 90.4%), wild boar (Sus scrofa, 78.3%), and Eurasian magpie (Pica pica, 51.5%), with control intensity differing among regions. In total, 87% of the questionnaire respondents declared controlling at least one predator species, while 49.3% employed gamekeepers to perform the control. In all surveyed regions, shooting was authorized, and it was the most frequent control method in hunting grounds for the aforementioned species (ranging from 76 to 100%), while the use of approved restraint methods was allowed in 11 regions but only used in 7 for foxes (8%) and magpies (25%). The control intensity (animals culled/km²) for foxes was higher when conducted by full-time keepers, while for magpies and wild boars, it was higher when conducted by hunters. The implementation of habitat management (agricultural and forest measures) that helps to reduce predation was higher in hunting grounds not conducting predator control. Based on our results, we propose a national predation management framework focused on controlling rather than removing predators. Full article

Serpulids are among the few annelid groups capable of building skeletal structures by secreting calcium carbonate. Compared with other biomineralizing organisms, their control over tube construction is relatively limited, making them vulnerable to environmental changes. To distinguish between intrinsic biological regulation and extrinsic environmental influence in tube formation, we examine the calcareous tube of Hydroides elegans, focusing on the tube ultrastructure, mineral composition, elemental distribution, organic-inorganic constituents, and biomineralization mechanism. The results show that the tube consists of three superimposed layers: an innermost organic sheet, an intermediate lamello-fibrillar calcite layer, and an outermost spherulitic prismatic calcite layer. The outer spherulitic prismatic layer frequently exhibits bioerosion, trapped sedimentary particles, and fan-shaped aragonite aggregates, indicating pronounced environmental influence. In contrast, the middle lamello-fibrillar calcite fabric is highly organized and closely integrated with the innermost organic sheet, indicating strictly biological controls. This study highlights the combined effect of biological controls and environmental influences in serpulid tube calcification, contributing to our understanding of their adaptive evolution in changing oceans. Full article

In the context of China’s “double carbon” goals, examining the spatial–temporal characteristics and influencing factors of the synergistic effect of pollution control and carbon reduction (SEPCR) in the Chengdu–Chongqing region (CCR) is crucial for advancing both air pollution (AP) control and carbon emissions (CE) mitigation. This study uses data on AP and CE from 2007 to 2022 and employs the coupling coordination degree (CCD) model, spatial autocorrelation analysis, and kernel density estimation to investigate the spatial–temporal distribution and dynamic evolution of the CCD between AP and CE in the CCR. Additionally, the Tobit regression model is applied to identify the key factors influencing this synergy. The results indicate that (1) during the study period, the air pollutant equivalents (APE) in the CCR showed a declining trend, while CE continued to increase; (2) the overall level of coupling coordination remained low, exhibiting an evolutionary pattern of initial increase, subsequent decrease, and then recovery, with synergistic effects showing slight improvement but significant fluctuations; (3) the SEPCR in the CCR was generally dispersed, exhibiting no significant spatial autocorrelation. A “core–periphery” structure emerged, with Chongqing and Chengdu as the core and peripheral cities forming low-value zones. Low–low clusters indicative of a “synergy poverty trap” also appeared; (4) economic development (PGDP), openness level (OP), and environmental regulation intensity (ER) are significant positive drivers, while urbanization rate (UR), industrial structure upgrading (IS), and energy consumption intensity (EI) exert significant negative impacts. Full article

Glyoxalase 1 (Glo1) functions as a catalyst that neutralizes methylglyoxal (MG), a highly reactive glycating agent predominantly produced during glycolysis—a metabolic pathway upregulated in cancer cells. MG primarily reacts with the amino groups of proteins (especially at arginine residues), leading to the formation of a major advanced glycation end product known as MG-derived hydroimidazolone 1 (MG-H1). We previously demonstrated in PC3 human prostate cancer (PCa) cells that the PTEN/PKM2/ERα axis promotes their aggressive phenotype by regulating the Glo1/MG-H1 pathway. In this study, after confirming our earlier findings, we investigated the downstream mechanisms of the PTEN/PKM2/ERα/Glo1/MG-H1 axis in controlling PC3 cell growth, focusing on the role of RAGE, a high-affinity receptor for MG-H1; hydrogen peroxide (H₂O₂); and Krev interaction trapped 1 (KRIT1), an emerging tumor suppressor. Using genetic approaches and specific inhibitors/scavengers, we demonstrated that the PTEN/PKM2/ERα/Glo1/MG-H1 axis promotes PC3 cell growth—measured by proliferation and etoposide-induced apoptosis resistance—through a mechanism involving MG-H1/RAGE pathway desensitization that leads to H₂O₂-mediated KRIT1 downregulation. These findings support and expand the role of PTEN signaling in PCa progression and shed light on novel mechanistic pathways driven by MG-dependent glycative stress, involving KRIT1, in this still incurable stage of the disease. Full article