Search Results (4,789)

Neurodegenerative diseases (NDs) are increasingly considered neurometabolic disorders driven by early mitochondrial dysfunction, neuroinflammation, and synaptic alterations that precede clinical symptoms. This review summarises pre-clinical and experimental evidence suggesting that intermittent fasting (IF) may influence these early pathogenic processes by promoting metabolic switching, enhancing autophagy and mitochondrial quality control, and modulating neuroimmune pathways. We discuss recent advances in biomarker research supporting the early detection of neurodegenerative changes, including ultrasensitive analytical platforms that can identify neuronal, glial, and synaptic injury during preclinical stages. By integrating these biomarker developments with findings from human and experimental intermittent fasting studies, we highlight how high-sensitivity assays provide quantifiable insights into the neurometabolic effects of fasting. Furthermore, we discuss how precision nutrition strategies incorporating multimarker panels, phenotypic and epigenetic signatures, and longitudinal multi-omics profiling may facilitate personalised intermittent fasting protocols and improve monitoring of biological responses. Overall, these findings underscore the relevance of a clinical biochemistry perspective integrating advanced biomarker technologies to evaluate the neurometabolic effects of intermittent fasting as a potential early neuroprotective strategy for individuals at risk of neurodegeneration. Full article

Objectives: The long-term effects of rheumatoid arthritis (RA) therapies on bone mineral density (BMD) remain incompletely characterized. We aimed to evaluate BMD trajectories over an 8-year follow-up in patients with RA treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biological DMARDs (bDMARDs) in real-world practice. Methods: Patients were selected from an observational RA cohort established at Nice University Hospital between 2001 and 2016. Participants were classified into two groups according to treatment regimen (csDMARD only or any bDMARD exposure). BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 1, 2, 3, 5, and 8 years at the lumbar spine, femoral neck, and total hip. Longitudinal changes in BMD were analyzed using multivariable linear mixed-effects models adjusted for age, sex, body mass index (BMI), disease duration, seropositivity, glucocorticoid use, anti-osteoporosis treatment, and clinical response. Results: A total of 312 patients were included, of whom 181 received bDMARDs and 131 were treated exclusively with csDMARDs. BMD showed limited change during the first two years in both groups. Beyond two years, modest declines were observed at hip sites at subsequent time points, whereas lumbar spine BMD did not demonstrate significant longitudinal change in pointwise analyses. In mixed-effects models, the treatment group–time interaction was significant for lumbar spine (p = 0.004) and total hip (p = 0.04), but not for the femoral neck (p = 0.34), indicating differential BMD trajectories over time between treatment groups. In the csDMARD group, lumbar spine and total hip BMD decreased by a mean of 0.0006 and 0.0005 g/cm² per month, respectively, whereas no significant slopes were observed in the bDMARD group. Older age was associated with lower BMD, while male sex and higher BMI were associated with higher BMD across sites. Conclusions: In this long-term real-world cohort, BMD remained relatively stable during the first two years of follow-up. Longitudinal analyses suggested a less pronounced decline in lumbar spine and total hip BMD trajectories among bDMARD-treated patients compared with those receiving csDMARD alone, underscoring the need for ongoing bone health monitoring in RA. Full article

The detection of biological markers is critical not only for the early diagnosis of cancer but also for adjustments in antitumor therapy. Rapid, sensitive, and selective detection and monitoring of the content of specific biomarkers in real time are key to point-of-care testing diagnostics. We report the detection of heat shock proteins by fluorescence immunoassay with the appropriate phage antibodies, with a minimum detection limit of 1 ng/mL. The fluorescence immunoassay data were confirmed by dot immunoassay and by circular dichroism studies. The results of the study may help in the adaptation of the fluorescence immunoassay to cancer diagnostics. Full article

Groundwater contamination caused by dense non-aqueous phase liquid (DNAPL) has long been recognized as a persistent environmental challenge, particularly in fractured porous media. DNAPL migration is highly uncertain due to the heterogeneity and complexity of fracture networks, which complicates risk assessment and remediation design. This paper begins with an overview of mathematical models for multiphase flow migration in fractured media, followed by a systematic analysis and classification of DNAPL migration mechanisms based on laboratory experiments and numerical simulations. Subsequently, key challenges in current DNAPL remediation practices are discussed, including difficulties in monitoring and characterizing fractured aquifers, limited delivery and utilization efficiency of remedial agents, and the back-diffusion of DNAPL from low-permeability zones. Based on this analysis, three primary DNAPL remediation approaches—physical, chemical, and biological methods—are reviewed and evaluated. Finally, future research directions for understanding DNAPL migration and improving remediation strategies in fractured media are proposed. Overall, this review bridges mechanistic knowledge, simulation research, and remediation practice, providing insights that contribute to future technological progress and management decision-making in DNAPL-contaminated fractured aquifers. Full article

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a biologically distinct entity, typically affecting younger, non-smoking patients and showing improved survival compared to HPV-negative tumors. Accurate HPV status determination is essential for correct staging, prognostic assessment, and treatment de-escalation. Despite advances, substantial variability persists among diagnostic methods and clinical workflows. A narrative review of PubMed, Scopus, and Web of Science databases was conducted up to July 2025. Studies addressing HPV detection techniques in OPSCC—including p16^INK4a^ immunohistochemistry (IHC), HPV DNA and RNA assays, liquid biopsy approaches, and computational surrogates—were critically analyzed regarding diagnostic accuracy, clinical applicability, and emerging innovations. Tissue-based assays remain the diagnostic reference standard. p16 IHC provides high sensitivity but limited specificity and should be confirmed with nucleic acid-based methods such as DNA PCR, in situ hybridization (ISH), or E6/E7 mRNA detection. Combined or “orthogonal” testing minimizes discordance and refines risk stratification. Liquid biopsy detection of circulating HPV DNA using droplet digital PCR or next-generation sequencing has shown high sensitivity and specificity in cohorts of patients with HPV-associated OPSCC, supporting its potential role as a complementary biomarker for treatment monitoring and surveillance. However, circulating HPV DNA alone does not unequivocally identify the anatomic source of HPV DNA and should be interpreted together with clinical, radiologic, and tissue-based findings. Oral rinse and saliva assays show moderate diagnostic performance, while artificial intelligence-based radiomic and histopathologic models are emerging as complementary tools. Reliable HPV attribution in OPSCC requires a multimodal diagnostic strategy integrating p16 IHC, molecular confirmation, and ctHPV-DNA monitoring. Methodological standardization and prospective validation are essential to implement precision-guided, cost-effective workflows in routine clinical practice. Full article

Low-accessible Cultural Heritage, including hypogeal sites, rupestrian architectures, and fragile structures, represents a major challenge for conservation, documentation, and continuous monitoring. These limitations stem from multiple inaccessibility factors, classified as physical (morphological complexity), asset risk (microclimatic instability), health and safety (structural vulnerability), managerial (lack of public access), and cognitive (lack of documentation). This research aims to transform digital models from mere representational tools into integrated cognitive and operational systems supporting decision-making and preventive conservation. The proposed methodological workflow is structured into five main phases: Preliminary Knowledge and Multidisciplinary Data Structuring (Ph1. PK–MDS), Comprehensive Digital Survey (Ph2. CDS), Development of Integrated Digital Models (Ph3. IDMs), Advanced Diagnosis and Monitoring (Ph4. ADM) and the implementation of an Integrated Digital Environment for Hypogeal Heritage Management (Ph5. IDE). Ph4 operates on two complementary scales: at the site scale, range-based point clouds enable the semi-automatic identification of extensive decay patterns, such as biological colonization. At the detail scale, the Random Forest algorithm enables the segmentation and quantification of material loss on frescoed surfaces through a diachronic comparison of historical and current data. Validated on the San Pellegrino complex in Matera, selected as a paradigmatic case study of low-accessibility hypogeal sites, representative of a broader system comprising approximately 150 rupestrian cult architectures, the methodology demonstrates how immersive digital environments function as shared knowledge spaces, supporting more informed, inclusive, and resilient heritage conservative management. Full article

Herbal melanin (HM), previously reported for its antiproliferative and pro-apoptotic properties, has garnered interest as a promising anti-colorectal cancer drug. However, HM’s biological effects and underlying molecular mechanisms and the related signaling pathways in colorectal cancer (CRC) cell motility are poorly investigated. To evaluate the impact of various concentrations (50, 100, and 200 μg/mL) of HM on cell migration, invasion, and tumorigenicity on human HT29 and SW620 CRC cell lines, a real-time cell analyzer instrument and colony formation assays were employed, respectively. An angiogenesis-related protein array was also used, and the levels of protein expression contributing to colony formation and extracellular proteolysis-driven cell migration and invasion, such as E-cadherin, N-cadherin and urokinase-type plasminogen activator receptor (uPAR), were monitored using Western blotting and RT-qPCR technologies. HM significantly decreased CRC cell motility, invasiveness, and formation of colonies, associated with E-cadherin upregulation and N-cadherin downregulation. In addition, HM specifically inhibited uPAR expression levels, which were also decreased by the pharmacological mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor UO126 and Jun N-terminal kinase (JNK) inhibitor SP600125, in both CRC cell lines, including metastatic CRC (mCRC) SW620 cell line. Addition of HM to cells pretreated with JNK and MEK inhibitors attenuated the blockade of JNK and ERK phosphorylation and alleviated HM-downregulated uPAR expression and HM-inhibited mCRC cell migration. In conclusion, our in vitro studies demonstrate that HM exhibits an inhibitory effect on CRC migration and invasiveness, associated with uPAR downregulation through JNK and ERK pathways. Full article

Excessive accumulation of copper ions (Cu²⁺) in the environment and biological systems poses severe risks to ecological balance and human health, necessitating accurate detection and monitoring of Cu²⁺. Schiff base derivatives with favorable optical properties provide an efficient strategy for copper ion recognition. In this paper, fluorescent probe L (5-methyl-2-hydroxybenzaldehyde-(7-diethylaminocoumarin-3-formyl) hydrazone) was synthesized through a three-step reaction using 4-diethylaminosalicylaldehyde and diethyl malonate as starting materials. The structure of probe L was confirmed by melting point analysis, infrared spectroscopy, and nuclear magnetic resonance. Single-crystal X-ray analysis revealed that probe L crystallized into a triclinic lattice with space group $P_1^{-}$. Optical investigations, including UV–Vis spectroscopy, fluorescence spectroscopy, and aggregation-induced emission studies, demonstrated highly sensitive and selective fluorescence “turn-off” behavior of probe L towards Cu²⁺ ions in DMSO, with negligible interference from other metal ions. Job’s plot and crystallographic analysis revealed a 1:1 binding stoichiometry between probe L and Cu²⁺, forming the complex [Cu(L)]. Fluorescence titration experiments revealed a binding constant (K_b) of 5.2 × 10⁶ L/mol and a detection limit of 7.8 × 10⁻⁷ mol/L, indicating excellent sensitivity. These results suggest that probe L has considerable promise for Cu²⁺ detection in aqueous environments, with potential applications in environmental monitoring and public health protection. Full article

Flexible conductive hydrogels hold great promise in wearable electronics and biomonitoring applications, yet their practical use is constrained by issues such as poor low-temperature tolerance, susceptibility to dehydration, and limited multifunctional sensing capabilities. This study successfully synthesized a dual-conductive lithium-ion and calcium-ion hydrogel based on acrylamide/gelatin via a simplified low-temperature one-pot polymerization method. At 60 °C, mixing acrylamide, gelatin, lithium chloride, and calcium chloride within 40 min constructed a network structure featuring covalent bonds, ionic bonds, and hydrogen bonds. The resulting material exhibited exceptional extensibility with a break elongation of 1408.5% and tensile strength of 134.2 kPa while maintaining strong adhesion to nine different substrates. It retained flexibility at −20 °C and demonstrated minimal mass loss (3% of initial value) after 10 days of aging. As a sensor, this hydrogel reliably responds to pressure, temperature, large-amplitude body movements, and subtle physiological signals like pulse and vocal cord vibrations. In animal simulation monitoring, its electrical resistance signals increased linearly with model body weight and remained stable between −20 °C and 20 °C. These results demonstrate the hydrogel’s broad application potential in wearable sensing, ecological monitoring, and smart agriculture. Full article

Background: Breaststroke performance in young swimmers is influenced by a complex interaction of anthropometric, physiological, and technical factors. However, existing studies predominantly focus on pre-selected or elite youth swimmers, limiting insight into performance development in non-elite populations without early selection bias. Purpose: This study aimed to identify key predictors of 50-m breaststroke performance and to examine longitudinal changes in selected characteristics in pre-adolescent, non-elite female swimmers. Methods: Fourteen female swimmers (baseline biological age: 10.52 ± 0.37 years) who entered swimming training without prior anthropometric or physiological selection were followed over three consecutive years. Measurements were collected at six time points and included anthropometric dimensions, body composition, aerobic and anaerobic capacity, respiratory volumes, and 50-m breaststroke performance. This investigation was a prospective longitudinal cohort study. Data were analysed using generalised estimating equations. Results: The correlation-filtered model explained 76% of the variance in 50-m breaststroke time. Chest depth (B = −0.16, p = 0.03), foot length (B = −0.17, p = 0.04), foot width (B = 0.30, p < 0.001), and shoulder width (B = −0.07, p = 0.04) emerged as significant anthropometric predictors. Maximal oxygen uptake also showed a significant association with performance (B = −0.33, p = 0.02). Conclusions: In pre-adolescent, non-elite female swimmers, selected anthropometric characteristics—particularly trunk dimensions and foot morphology—are associated with short-distance breaststroke performance. Aerobic capacity appears to play an indirect, supportive role. These findings highlight the importance of longitudinal monitoring without early selection and support a development-oriented approach to youth swimming training. Full article

Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are biologically distinct hematologic malignancies with heterogeneous clinical courses, and minimally invasive molecular biomarkers are needed to support blood-based discrimination. We performed a comprehensive in silico analysis to derive cross-cohort, direction-consistent transcriptomic programs for CLL and MM and to nominate regulatory microRNAs (miRNAs) linked to these signatures. Public gene-expression datasets from the NCBI Gene Expression Omnibus (two cohorts per disease) were processed with a reproducible workflow to define disease-biased consensus gene sets. Experimentally validated miRNA–target interactions from miRTarBase were integrated with consensus genes for miRNA target over-representation analysis, and miRNA–mRNA networks were constructed to prioritize candidate miRNAs by connectivity. A strict intersection strategy yielded a large, direction-consistent CLL consensus program, whereas a vote-based approach produced a smaller MM program due to a weaker signal in one cohort. Enrichment and network analyses identified compact regulatory modules in CLL, including a highly connected candidate miRNA linked to many CLL-up genes. This framework provides reproducible disease-biased gene programs and evidence-anchored miRNA candidates to support targeted experimental validation and the development of hypothesis-driven blood-based biomarker studies for differential diagnosis and monitoring. Full article

Telemedicine, driven by the Internet of Things (IoT) and wireless connectivity, is essential for managing cardiovascular diseases, where hypertension remains the primary risk factor. In preclinical research, rabbits are superior biological models compared to rodents due to their human-like lipid metabolism. However, continuous blood pressure monitoring in this species remains challenging. The gold-standard technique (direct carotid catheterization) requires terminal procedures, and indirect methods (Doppler, oscillometric) show limited agreement with direct measurements. Furthermore, commercially available implantable telemetry platforms, while enabling real-time monitoring in freely moving animals, require costly surgical implantation, specialized proprietary hardware, and post-operative recovery periods that may confound early hemodynamic data. To address these limitations, this study presents a low-cost, customizable, and minimally invasive monitoring system utilizing a pressure transducer in the central auricular artery. The device integrates an ESP32 microcontroller with IoT technology for digital signal processing and seamless wireless data transmission to the ThingSpeak cloud platform. Unlike implantable telemetry, the proposed approach avoids surgical implantation and its associated costs and recovery time, while still enabling continuous, real-time hemodynamic tracking throughout the experimental period. A pilot evaluation against the BIOPAC MP100 reference (carotid artery) demonstrated relative errors of 1.60% for mean arterial pressure, 8.58% for systolic blood pressure, and 2.43% for diastolic blood pressure. By reducing invasiveness and enhancing remote data accessibility, this system provides a promising framework for the preclinical evaluation of antihypertensive agents and cardiovascular mechanisms, bridging the gap between edge computing and remote clinical diagnostics. Full article

Urban wetlands are acoustic hotspots where vegetation structure, hydrological dynamics, and anthropogenic noise interact, yet multi-season assessments of how vegetation influences avian soundscapes are limited. This study explored bird soundscape dynamics across forest, open forest grassland, and meadow habitats in Nanjing Xinjizhou National Wetland Park, eastern China, using passive acoustic monitoring during spring and autumn 2023. Twelve sampling points (four per vegetation type) were established, and six acoustic indices were calculated, including the Acoustic Complexity Index (ACI), Acoustic Diversity Index (ADI), Acoustic Evenness Index (AEI), Bioacoustic Index (BIO), Normalized Difference Soundscape Index (NDSI), and Acoustic Entropy Index (H). were calculated from 48-h recordings each season. Random forest models and redundancy analysis assessed the relationships between acoustic indices, fine-scale vegetation parameters (e.g., crown width, tree height, species richness), and anthropogenic factors (e.g., distance to roads/trails, surface hardness). Vegetation structure, particularly crown width, was the primary driver of avian acoustic diversity, with broad-crowned forests consistently exhibiting the highest acoustic complexity. In spring, anthropogenic factors such as trail and road proximity dominated soundscape variation, suppressing biological sounds. In autumn, with reduced human presence, vegetation structure emerged as the dominant factor, while bioacoustic activity remained elevated despite reduced peaks in acoustic complexity. Proximity to roads increased low-frequency (1–2 kHz) noise and suppressed mid-frequency (4–8 kHz) bird vocalizations, but trees with crown widths ≥4 m maintained higher acoustic diversity even near disturbance sources. This study demonstrates that vegetation structure mediates both resource availability and sound propagation, buffering the effects of anthropogenic disturbance in frequency-specific ways. Multi-season sampling is crucial for understanding the dynamic interplay between vegetation phenology and human activity that shapes urban wetland soundscapes. Full article

Phytoecdysteroids have garnered increasing interest due to their broad biological and pharmacological properties. The present study reports on the development and validation of a reliable liquid chromatography–mass spectrometry method for the detection and quantification of 20-hydroxyecdysone, turkesterone, and ponasterone. The optimized procedure improved ionization efficiency and chromatographic resolution through gradient elution using 0.1% formic acid in water and acetonitrile. Data acquisition in selective ion monitoring modes ensured high analytical precision, reproducibility, and sensitivity. The method demonstrated excellent linearity, accuracy, repeatability, and low detection limits, making it suitable for routine phytochemical and quality control applications. Application of the method to extracts from nutrient-rich superfoods, including kaniwa, spinach, quinoa, and asparagus, confirmed these plants as natural sources of phytoecdysteroids. Additionally, thirteen commercially available dietary supplements labeled as containing extracts of Rhaponticum carthamoides, Cyanotis arachnoidea, Ajuga turkestanica, or ecdysteroids were analyzed. Several products standardized to 80–95% ecdysterone contained substantially lower amounts than declared, with measured 20-hydroxyecdysone levels ranging from below the limit of detection to approximately 50 mg per capsule, whereas some non-standardized products exhibited moderate to high levels, reaching up to approximately 105 mg per capsule. Variability in turkesterone content was also observed among products marketed as standardized extracts. The method provides a simple, reliable, and accessible approach for the quantitative analysis of major phytoecdysteroids in complex plant matrices and dietary supplements. Its implementation may support phytochemical research, routine quality control, and anti-doping monitoring of ecdysteroid-containing products. Full article

Background: Urticaria, particularly chronic urticaria (CU), is a highly prevalent inflammatory skin disorder characterized by recurrent wheals and/or angioedema with a fluctuating and unpredictable course that significantly impairs quality of life and requires long-term monitoring. Despite established therapeutic guidelines, disease control remains suboptimal in a considerable proportion of patients. Telemedicine has emerged as a promising adjunctive strategy for chronic disease management. This review aims to critically evaluate the role, applications, benefits, and limitations of telemedicine and digital health interventions in urticaria management. Methods: A scoping review of the literature was conducted focusing on studies addressing telemedicine, digital patient-reported outcomes, mobile health applications, and remote monitoring strategies in urticaria. Evidence from pandemic and post-pandemic telemedicine models was also analyzed to identify transferable approaches. Results: Telemedicine demonstrates significant potential in urticaria management by enabling structured symptom monitoring, facilitating remote follow-up during therapeutic escalation (including biologic therapies), improving patient empowerment and adherence, and reducing healthcare utilization and indirect costs. Digital tools such as electronic diaries and validated PRO-based applications support continuous disease assessment. However, telemedicine cannot replace direct clinical examination, and limitations include diagnostic uncertainty, digital inequalities, data privacy concerns, and lack of large disease specific trials. Conclusions: Telemedicine represents a valuable complementary and integrative model for urticaria care, particularly suited for chronic disease monitoring. Hybrid care pathways combining remote and in-person management appear to be the most effective and sustainable strategy. Further high-quality urticaria-specific studies and standardized digital frameworks are required to optimize its clinical implementation. Full article