Search Results (9,360)

Dynamic response measurements support bridge monitoring and structural assessment because they are obtainable under operational loading and are sensitive to changes in stiffness, boundary conditions, and mass distribution. This article presents a structured scoping review of dynamic-response-based bridge monitoring and assessment. It covers damage-sensitive indicators, stiffness/capacity proxy inference, interpretation under operational and extreme loading, sensing with acquisition (contact, and indirect/drive-by), and data processing, machine learning and digital-twin integration for decision support. Evidence was identified through targeted searches in Scopus and The Lens with duplicate resolution in Zotero. The cited studies are compiled into a traceable evidence inventory linked to method families and decision objectives. The synthesis shows that global modal properties enable change screening but are highly confounded by environmental/operational variability. Localization and state characterization typically require denser or higher-fidelity sensing and signal conditioning. Finally, capacity-related inference using calibrated conversion models or machine learning (ML) surrogates remains context-bounded and validation-dependent. This review provides an end-to-end pipeline, evidence-maturity rubric, and conservative failure-mode checks with escalation logic that tie SHM outputs to inspection and analysis rather than direct condition declarations for bridge owners. This review is intentionally scoped and does not claim PRISMA-style comprehensiveness. Full article

Pressure fluctuations caused by a jet in crossflow (JICF) can induce cavitation and potentially damage wall surfaces. In mercury targets for a pulsed spallation neutron source, where cavitation damage progresses due to thermal shock, mercury is confined within a vessel that incorporates a double-wall structure—comprising a narrow channel and a main flow channel—to form parallel flows and suppress damage. However, as the damage progressed, penetration holes were formed in the inner wall separating these flows, and characteristic damage patterns were observed that suggest accelerated damage progression caused by JICF, in which a jet flows from the narrow channel into the main channel. The mechanism underlying this phenomenon has not been fully clarified. Therefore, the flow field and pressure fluctuations around the penetration hole were evaluated using PIV measurements in a water loop and numerical simulations of single-phase flow, with varying jet velocity and jet width. The results revealed that inflow through the penetration in the inner wall generates JICF, which produces vortices downstream of the inflow jet and induces pressure fluctuations that may be associated with cavitation. Full article

Virus-like particles (VLPs), nanoscale self-assembled structures lacking viral genetic material, have emerged as a versatile platform for vaccines, targeted delivery systems, and gene-editing applications owing to their strong immunogenicity, favorable biosafety profile, and high engineerability. However, the complex architecture of VLPs, their significant size heterogeneity, and the diversity of process- and product-related impurities generated in different expression systems make downstream purification a major bottleneck limiting product quality, yield, and manufacturability. This review systematically discusses advanced downstream purification strategies for VLPs from the perspective of three major objectives: preservation of structure and biological activity, control of product heterogeneity, and assurance of viral safety. First, strategies for maintaining VLP integrity and function are examined, including optimization of solution conditions, adoption of gentle yet efficient separation operations, and integration of process analytical technology (PAT) to reduce process-induced damage. Second, the review summarizes multi-step purification approaches—spanning clarification, ultrafiltration/diafiltration (UF/DF), chromatography, and disassembly/reassembly—to remove host cell proteins, host cell DNA, and product-related impurities while improving particle homogeneity and stability. Third, viral safety is discussed primarily from the perspective of downstream virus clearance under host-dependent risk, with particular attention to orthogonal clearance steps tailored to VLP properties and expression systems such as CHO cells and insect cell–baculovirus platforms. Overall, this review provides a CQA-oriented framework and practical guidance for the development of robust, scalable, and GMP-compliant downstream purification processes for VLP-based products. Full article

Background/Objectives: The medial meniscus is crucial for load transmission and knee stability. Meniscal tears disrupt joint biomechanics, increasing the risk of cartilage degeneration. However, few studies have quantitatively compared how different tear types affect stress and contact mechanics using finite element analysis (FEA). This study aims to analyze stress distributions for various meniscal tear types and develop a predictive model for meniscal stress behavior. This study investigates how stress distributions differ between healthy and torn medial menisci under identical loading conditions. The study examines which meniscal tear type produces the highest stress concentrations. The effects of different tear types on penetration, gap formation, pressure distribution, and sliding distance at the meniscus interface are also analysed. Materials and Methods: The FEA model of the knee joint, including femoral and tibial cartilage and the medial meniscus, was developed. Simulations were conducted for a healthy meniscus and for menisci with radial, horizontal and complex tears. Stress, penetration, gap, pressure, and sliding distance were calculated, and a mathematical model describing their relationships was established. Results: All torn menisci exhibited significantly higher stresses than the healthy meniscus (p < 0.001). Radial tears generated the highest stress concentrations (p < 0.001). Pressure was mainly influenced by meniscal geometry, while the gap remained nearly constant. Penetration increased slightly (p < 0.05). The predictive model demonstrated a strong correlation between meniscal stress and interface parameters (R² > 0.9). In a healthy meniscus, stress distribution is homogeneous (≈26 MPa). Stress concentration increases depending on the tear type: limited in a horizontal tear (≈26.5 MPa), significant in a vertical tear (≈30.8 MPa), and highest in a radial tear (≈40.6 MPa). These results indicate that as the tear progresses, the load-bearing capacity of the meniscus decreases, and stresses concentrate at the tear edges. Conclusions: Meniscal tears, especially radial ones, substantially alter knee biomechanics and elevate tissue stress. These biomechanical insights highlight the importance of early diagnosis and targeted rehabilitation strategies to prevent further cartilage damage and osteoarthritis progression. Full article

To address the prominent fatigue failure risk of planetary gears in power-split hybrid buses and the lack of quantitative damage analysis across various operating modes in existing studies, this paper focuses on the front planetary gear set of a power-split hybrid bus. Based on a full-vehicle co-simulation model, loads under full operating conditions are decomposed into 11 operating modes, mode-switching loads are analyzed and extracted, and mode-decomposed and mode-switching fatigue loading spectra are compiled. Fatigue simulation is then conducted using Miner’s linear damage accumulation rule. Results show that the sun gear directly coupled to motor is the system’s most fatigue-susceptible component, exhibiting significant asymmetric unilateral tooth flank damage. The hybrid electric vehicle (HEV) mode contributes approximately 88% of total damage to the sun gear’s right flank, dominating system fatigue damage. Transient mode-switching conditions account for approximately 60% of total damage to the sun gear’s left flank, serving as the core damage source. Compared with the traditional full-condition merging method, the proposed mode-decomposed method improves the conservatism of life prediction. This work provides methodological support for refined strength design and targeted optimization of power-split hybrid transmission systems. Full article

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) represents a dynamic and multistage pathological process driven by maladaptive intercellular communication. Rather than resulting from isolated cellular injury, AKI-CKD progression unfolds through a spatially and temporally coordinated dysregulation of cellular networks. In the acute phase, damaged tubular epithelial cells act as instigators, releasing damage-associated molecular patterns (DAMPs) and activating a storm of inflammatory crosstalk among immune cells, endothelium, and fibroblasts. During the subacute repair phase, imbalance in macrophage polarization (M1 persistence/M2 dysfunction) and the emergence of senescent tubular cells with a senescence-associated secretory phenotype (SASP) together create a pro-fibrotic microenvironment. In the chronic phase, activated myofibroblasts—derived from multiple sources—establish self-sustaining feedback loops via autocrine signaling, mechanical memory from the stiffened extracellular matrix (ECM), and ongoing dialogue with immune and resident cells, ultimately leading to irreversible fibrosis. Current therapeutic strategies focused on single molecular targets often fail to disrupt this resilient network homeostasis. Therefore, we propose a paradigm shift toward spatiotemporally precise network-remodeling therapies, which require integrated use of liquid biopsy-based staging, smart nanocarriers for cell-specific delivery, and AI-powered multi-omics modeling. This review systematically delineates the evolving cell-to-cell communication networks across AKI-CKD continuum and highlights innovative strategies to intercept disease progression by targeting the pathophysiology of cellular crosstalk. Full article

Wildfire occurrence in temperate Europe is increasingly shaped by the interaction of human activities and short-term climatic anomalies rather than by natural ignition processes alone. This study analyses national wildfire statistics from Slovakia covering the period 2010–2025 to investigate temporal trends in wildfire occurrence, ignition causes, and fire-related impacts, including economic damages and human casualties. Official fire records provided by the Fire Research Institute of the Ministry of the Interior of the Slovak Republic were analyzed using descriptive and exploratory statistical methods. The dataset includes annual information on wildfire frequency, detailed ignition cause classifications, direct economic losses, fatalities, and injuries. European-scale wildfire patterns were considered for contextual comparison using data from the European Forest Fire Information System (EFFIS). Results show that wildfire occurrence in Slovakia is overwhelmingly dominated by human-caused ignitions, with negligence-related activities forming a persistent baseline of ignition pressure throughout the study period. The extreme wildfire year 2012, during which more than 11,000 wildfire events were recorded, illustrates how routine human behaviors can be strongly amplified under climatically favorable conditions without altering the underlying cause structure. Importantly, wildfire impacts were found to be weakly correlated with fire frequency, as years with moderate numbers of fires occasionally generated disproportionately high economic damages and casualties. These findings demonstrate that wildfire risk in Slovakia is primarily driven by behavioral ignition patterns modulated by short-term climatic variability. The results support a shift towards prevention-oriented and impact-focused wildfire risk management strategies, consistent with current European policies emphasizing integrated risk assessment, early warning, and targeted prevention in temperate regions. Full article

Hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase, a key acyltransferase in the phenylpropanoid pathway and a canonical member of the BAHD acyltransferase family (BAHD), catalyzes the formation of pivotal intermediates in the biosynthesis of secondary metabolites such as lignin, chlorogenic acid, and flavonoids. These compounds serve indispensable protective functions in terrestrial plants, underpinning their adaptive responses to abiotic stresses such as drought, ultraviolet (UV) radiation, and oxidative damage. Although the role of HCT/HQT in the core phenylpropanoid pathway has been extensively characterized, its precise functional contributions to the flavonoid biosynthetic branch—particularly with respect to substrate selectivity, kinetic regulation, and metabolic channeling—remain incompletely understood. This review systematically analyzes the structural features, spatial conformation, catalytic mechanism, and substrate promiscuity of HCT/HQT to clarify its molecular determinants of activity and specificity. Furthermore, it highlights regulatory factors influencing HCT/HQT gene expression, such as transcription factors (MYB, bHLH, WRKY), phytohormones (GA₃, Eth, MeJA, 6-BA, MT), and abiotic/biotic stressors (temperature, blue light, nitric oxide, nano-selenium). Collectively, these insights illuminate how plants dynamically fine-tune phenylpropanoid metabolism in coordination with developmental programs and environmental challenges. This work provides a foundation for further research on HCT/HQT and supports efforts to develop improved crop varieties through targeted regulation of this central metabolic node. Full article

Ultraviolet (UV) irradiation induces complex skin damage, including hyperpigmentation, oxidative stress, and alterations in proteins related to keratinocyte differentiation and epidermal barrier-associated status. This study investigated the multifunctional protective effects of Padina arborescens ethanolic extract (PAEE) against skin damage in melanocytes, keratinocytes, and zebrafish. In alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells, PAEE effectively suppressed the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling pathway, which was associated with reduced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, leading to decreased melanin synthesis. PAEE also exhibited photoprotective properties by reducing reactive oxygen species (ROS), inhibiting interleukin-1 beta (IL-1β), and attenuating matrix metalloproteinase-1 (MMP-1) upregulation associated with UVB (ultraviolet B)-induced photodamage in HaCaT keratinocytes. Notably, PAEE restored the UVB-reduced expression of filaggrin and involucrin, representative markers of keratinocyte differentiation and epidermal barrier-associated status, in HaCaT keratinocytes. In zebrafish embryos, PAEE suppressed α-MSH-induced melanin accumulation and UVB-induced ROS generation at non-toxic concentrations. Taken together, these results suggest that PAEE exerts anti-melanogenic and photoprotective effects in cellular and zebrasfish models and may serve as a promising marine-derived ingredient for cosmeceutical applications targeting UVB-related skin damage. Full article

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the microbiota-gut-brain axis. Objective: This systematic review aims to comprehensively evaluate the role of the microbiota-gut-brain axis in Alzheimer’s disease, with a particular focus on its mechanistic links to oxidative stress, mitochondrial dysfunction, and amyloid pathology, as well as its therapeutic potential. Methodology: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, focusing on studies evaluating gut microbiota composition, metabolomic changes, oxidative stress markers, mitochondrial activity, and therapeutic interventions in AD models and patients. Results: Altered gut microbial composition in AD is associated with increased pro-inflammatory taxa (Escherichia-Shigella, Bacteroides) and depletion of short-chain fatty acid (SCFA) producing bacteria (Faecalibacterium, Roseburia). Dysbiosis contributes to systemic inflammation, disrupted intestinal permeability, and microglial activation, leading to oxidative damage and mitochondrial impairment in neurons. Preclinical and clinical studies indicate that probiotics, prebiotics, and fecal microbiota transplantation can restore redox balance, reduce neuroinflammation, and improve cognitive outcomes. Multi-omics and AI-based models are emerging as tools for identifying microbiome-derived biomarkers for early AD detection. Conclusion: The gut microbiota-mitochondria-oxidative stress axis represents a promising therapeutic target in Alzheimer’s disease. Future research should focus on longitudinal human studies, standardized microbial profiling, and personalized microbiome-based interventions to translate these mechanistic insights into clinical benefit. Full article

A distinct form of chronic kidney disease of unknown etiology (CKDu) has emerged in tropical regions of Sri Lanka, predominantly affecting individuals aged 30–60 years in the North Central Province. Unlike conventional chronic kidney disease (CKD), CKDu occurs independently of diabetes or hypertension and is characterized by tubulointerstitial damage, including tubular atrophy, interstitial inflammation, and fibrosis. Epidemiological studies showed familial clustering, suggesting an underlying genetic predisposition. This study aimed to identify genetic variants associated with CKDu in Sri Lankan populations using whole-exome sequencing (WES). Eighty-six individuals (47 CKDu patients and 39 controls) were recruited from endemic and non-endemic regions. Physiological, biochemical, and geographic parameters were recorded. DNA extracted from blood was subjected to WES to identify variants associated with CKDu. Results: A total of 171 unique variants across 121 genes were identified. Among the most prevalent genes were ATXN3, LFNG, PNLDC1, LINC02456, and HLA-DRB1. In the case–control comparison, only LFNG showed statistically significant enrichment in affected individuals, whereas signals in ATXN3, PNLDC1, and LINC02456 were not statistically significant, but have an association with renal dysfunction, and thus are included as hypothesis-generating variant observations. HLA-DRB1 variants showed trends toward a protective haplotype. LFNG showed the greatest prevalence in affected individuals (71.7%), followed by PNLDC1 (63%), ATXN3 (56%), FIP1L1 (41%), and HLA-DRB1 (32%). Conclusion: Findings suggest genetic variants in combination with environmental factors may contribute to CKDu susceptibility in the Sri Lankan population. We underscore the multi-factorial nature of CKDu and highlight the need for integrative genomic and environmental research to elucidate disease mechanisms and inform targeted prevention strategies. Full article

Primary Sjögren’s disease (SjD) is characterized by lymphocyte infiltration into exocrine glands. Mitochondrial dysfunction is a critical pathological mechanism underlying SjD, and mitophagy plays a vital role in clearing damaged mitochondria. This study used bioinformatic analysis to explore the potential roles of mitophagy-related genes in SjD pathogenesis and immune infiltration. Bioinformatic analysis was performed on the SjD microarray datasets to identify differentially expressed genes (DEGs). Mitophagy-related DEGs were selected and analyzed using functional enrichment, protein–protein interaction (PPI) networks, and machine learning (Least Absolute Shrinkage and Selection Operator [LASSO] and Random Forest) to identify hub genes. Their diagnostic value was assessed by receiver operating characteristic (ROC) curves. Immune infiltration and its correlation with hub genes were also evaluated. Hub gene expression in the salivary glands of patients was validated using qRT-PCR. Regulatory networks were also predicted. Three hub genes (GABARAPL1, PINK1, and SQSTM1) were identified. They showed high diagnostic specificity and were downregulated in SjD salivary glands. Immune infiltration analysis revealed increased levels of activated natural killer (NK) cells, memory B cells, plasma cells, CD8+ T cells, Tfh cells, and M1 macrophages, but decreased levels of Tregs and M2 macrophages. Hub gene expression was correlated with specific immune cell subsets. Regulatory network predictions highlighted potential upstream regulators and therapeutic compounds. This study identified three mitophagy-related hub genes linked to immune dysregulation in SjD, providing novel insights into disease mechanisms and potential therapeutic targets. Full article

Soil salinization is a major threat to global crop production. Tartary buckwheat (Fagopyrum tataricum), valued for its hardiness in marginal environments, provides an excellent system for studying plant salt tolerance. Using an integrated multi-omics approach, we deciphered the physiological, metabolic, and transcriptional responses of Tartary buckwheat to prolonged NaCl stress. Physiological profiling confirmed membrane damage alongside osmotic adjustment via proline accumulation and a phased antioxidant response. Metabolomics revealed extensive reprogramming, with dynamic enrichment in pathways of flavonoid biosynthesis, lipid metabolism, and the TCA cycle. Transcriptomics delineated a time-specific cascade from early signaling to late defense activation. Critical regulators within ABA and MAPK signaling pathways showed fine-tuned, divergent expression; for instance, SnRK2.3 was suppressed while specific PP2Cs were induced, and FtMAPK10 was dramatically up-regulated. Integrated analysis demonstrated coordinated induction of osmoprotectant synthesis (e.g., galactinol and betaine pathways) and a rewiring of central carbon metabolism. Our findings reveal a sophisticated, multi-layered adaptation strategy in Tartary buckwheat, integrating enhanced osmolyte production, antioxidant defense, membrane remodeling, and metabolic reprogramming, orchestrated by key signaling networks. This study provides a comprehensive molecular framework for salt tolerance and identifies valuable genetic targets for improving crop resilience. Full article

Arsenic exposure increases lung cancer risk, yet its molecular mechanisms remain unclear but are linked to peroxisome proliferator-activated receptor gamma (PPARγ). We investigated PPARγ-related molecules affected by sodium arsenite (NaAR) in non-small cell lung cancer (NSCLC) cells using immunochemical, gene knockdown, and immunoprecipitation approaches. PPARγ was critical for NSCLC growth, as high PPARγ-expressing A549 cells proliferated more than low-expressing H1299 cells after NaAR treatment. In A549 cells, NaAR upregulated polyubiquitinated PPARγ, activating cell cycle arrest and DNA damage response pathways. Rather than inducing significant caspase-dependent apoptosis, NaAR activated nuclear factor-kappa B and downregulated mixed lineage kinase domain-like (MLKL) via K63-linked polyubiquitinated receptor-interacting protein kinase 1, thereby inhibiting apoptosis and necroptosis. PPARγ knockdown or NAD⁺ supplementation induced PARP-1 hyperactivation and MLKL upregulation, leading to DNA damage and necroptosis. PARP-1 inhibition by 3-aminobenzamide induced apoptosis, indicating that PPARγ regulates apoptosis and necroptosis through PARP-1 activation. Proteasome inhibition increased polyubiquitinated PPARγ but not p53. Leptomycin B induced PPARγ degradation and p53 accumulation, promoting necroptosis and apoptosis, suggesting cytoplasmic p53 contributes to cell death. p62 interacted with PPARγ and p53, and its knockdown suppressed their NaAR-induced upregulation. In conclusion, NaAR-induced PPARγ promotes A549 cell survival by enhancing DNA repair and inhibiting apoptosis and necroptosis via cooperation with p53 and p62, highlighting PPARγ as a potential therapeutic target. Full article

Ferroptosis is an iron-dependent cell death driven by lipid peroxidation and failure of cellular antioxidant defenses. It is triggered by oxidative stress and can be aggravated by aging, inflammation, and dysregulation of iron homeostasis. In the central nervous system, iron dyshomeostasis, mitochondrial dysfunction, and membrane lipid remodeling can amplify oxidative injury and increase susceptibility to ferroptotic damage, particularly in vulnerable neurons. There is growing evidence that ferroptosis-related processes are linked to Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis. This review addresses novel approaches to track ferroptosis in vivo, such as imaging and biomarker techniques, and important molecular mechanisms linking iron metabolism, reactive oxygen species, and PUFA-driven lipid peroxidation to neuronal damage. We also explore upstream transcriptional control via NRF2, iron chelation and iron-handling modulation, inhibition of lipid peroxidation, and reinforcement of the System Xc-GSH-GPX4 and CoQ10-linked defense pathways. Subsequently, we highlight translational issues that need attention to further progress ferroptosis-targeted therapies for neurodegenerative disease. Full article