Search Results (715)

An approach based on a multi-relaxation (MR) test, in conjunction with a spring-dashpot model for data analysis, was employed to evaluate the influence of hydrothermal treatment at 65 °C on the viscous and quasi-static stress responses of polycarbonate (pure PC) and its short glass fibre composite (GF-PC) during the relaxation stages. The findings indicate that while this hydrothermal treatment did not affect the ductility of pure PC, it resulted in a significant ductility decrease in GF-PC. Furthermore, results from the modelling indicated that a parallel three-branch model was sufficient to simulate the stress decay during the relaxation stages of pure PC, but an additional branch (designated as the M-branch) was required for GF-PC. The study also found that for GF-PC, the hydrothermal treatment led to a distinct increase in the viscous stress response of the M-branch, but not in the other two viscous branches. This phenomenon is believed to stem from the coexistence of two types of PC matrix in GF-PC: one influenced by the presence of fibres and the other unaffected. Without the hydrothermal treatment, both types of PC matrix exhibit a similar deformation-dependence (based on stroke of the test machine) in their stress response; however, because the hydrothermal treatment affects the strength at the fibre–matrix interface, the stress responses of the two matrix types differ during relaxation. Consequently, the M-branch is believed to capture the altered stress response of the fibre-influenced PC matrix. The study concludes that under the investigated hydrothermal conditions, the reinforcing effect of the short fibre on the mechanical strength of GF-PC could be lost. Therefore, the addition of short glass fibre does not inherently guarantee mechanical reinforcement of PC. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an idiopathic, multisystem disorder marked by debilitating fatigue, post-exertional malaise, cognitive dysfunction and neuroinflammation. Its etiology remains unclear, yet emerging evidence implicates a complex interplay between immune dysregulation, metabolic impairment, mitochondrial bioenergetics, and environmental stressors such as viral infection or low-dose ionizing radiation (LDIR). To develop treatments for ME/CFS, it is essential to identify suitable targets for therapy. In this narrative review, we discuss recent findings on the overlap of ME/CFS with LDIR effects and examine potential mechanistic links that may arise from LDIR-induced bystander effects (RIBEs). We highlight potential candidate biomarkers that bridge these domains: mitochondrial respiratory dysfunction, altered ornithine transport via SLC25A15 (ORNT1), possible roles of CD38 in the context of immunity and NAD+ depletion, cyclin D1–dependent metabolic reprogramming and modulation of gene expression, and α-synuclein as a potential neuroinflammatory damage-associated molecular pattern (DAMP). While the involvement of these biomarkers in ME/CFS is yet to be confirmed experimentally, evidence from in vitro studies of irradiated cells, exosome profiling, and patient samples suggests that RIBEs can, in theory, produce prominent cellular ME/CFS phenotypes through associated mechanisms, including those exhibiting oxidative stress, impaired ATP production, and immune modulation. We propose a hypothetical, exploratory model wherein LDIR initiates or contributes to adaptive metabolic shifts (including CD38 upregulation and cyclin D1 stabilization) that, coupled with persistent bystander signaling, could potentially culminate in chronic fatigue and neurocognitive symptoms in some reported ME/CFS cases. Finally, we outline a research agenda encompassing the establishment of standardized diagnostic criteria, multi-omics profiling of patient cohorts, exosome analysis, functional mitochondrial assays, and targeted therapeutic trials focusing on possible anti-CD38 antibodies and NAD+ precursor therapy. By integrating recent findings in low-dose radiation biology with ME/CFS pathophysiology, this review aims to promote interdisciplinary investigations that may uncover mechanistic insights and novel biomarkers for diagnosis and treatment of ME/CFS. We further review steps in a proposed model taking us from low-dose radiation exposure to a number of possible targets. Full article

Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy arising from a single-nucleotide transversion (GAG → GTG) at codon six of the HBB gene on chromosome 11, substituting glutamic acid with valine in the β-globin chain and producing hemoglobin S (HbS). Under hypoxic conditions, HbS polymerizes and distorts erythrocytes into the characteristic sickle shape, initiating a cascade of vaso-occlusion, chronic hemolytic anemia, and progressive multi-organ damage that defines the clinical burden of this disease. Although SCD has ancient origins in sub-Saharan Africa, the Indian subcontinent, the Middle East, and the Mediterranean, regions where it conferred heterozygous resistance to malaria, the ease of human migration has long since made it a global health concern, affecting an estimated 300,000–400,000 newborns annually. Advances in molecular and genomic research have deepened our understanding of SCD pathophysiology, revealing the central contributions of hemoglobin polymerization, oxidative stress, endothelial inflammation, and nitric oxide depletion to disease progression. Current management rests on supportive pharmacological interventions, including hydroxyurea, chronic transfusion therapy, L-glutamine, and multimodal pain management, complemented by lifestyle modifications. Curative approaches have advanced substantially: hematopoietic stem cell transplantation (HSCT) remains the established standard of cure, while the regulatory approvals in late 2023 of the CRISPR/Cas9-based exagamglogene autotemcel (Casgevy) and the lentiviral vector-based lovotibeglogene autotemcel (Lyfgenia) represent the most transformative development in the history of SCD therapeutics. This review traces the disease from its ancient origins and molecular characterization through to its clinical manifestations, inheritance patterns, screening strategies, and the full spectrum of current and emerging therapies. Persistent challenges, prohibitive treatment costs, healthcare inequities, the ethical dimensions of genome editing, and the urgent need for long-term safety data, are examined critically, with a view to informing the research and policy agenda that must accompany these remarkable scientific advances. Full article

The decline in cultivating crops like lupin in the Arab region and globally is due to climate change, old local varieties with low yield, and the long cultivation season that delays subsequent crops. This study tested a treatment protocol using zinc sulfate, salicylic acid (SA), and aloe vera extract on three Egyptian varieties: Giza 1, Giza 2, and Giza 3. A multi-environment trial was conducted over two seasons across two contrasting locations. Advanced linear mixed-effects modeling revealed that genotype was the dominant source of phenotypic variance, accounting for 5.8% and 4.9% of the variation in days to blooming (DTB) and days to maturity (DTM), respectively. SA was the most effective, significantly reducing DTB by 10.7% (7.9 days) and DTM by 5.9% (9.8 days) compared to the control. A significant genotype × treatment interaction (p < 0.001) identified Giza 2 as the most responsive cultivar, achieving the shortest DTB (60.0 days) under SA. Variance component and AMMI stability analyses confirmed strong environmental modulation, with treatment efficacy amplified at the site with greater abiotic stress potential. However, Giza 3 with zinc sulfate offers stable performance under high-fertility conditions. Such results suggest that the careful management of genotypes and diverse stimuli under continuous environmental changes can significantly accelerate growth and enhance adaptability, thereby achieving stability and increasing productivity. Full article

Inflammation and oxidative stress induced by high glucose levels constitute essential factors impeding wound healing in diabetes, posing a significant threat to public health. Despite its notable anti-inflammatory and antioxidant potential, the clinical applicability of quercetin is hampered by its hydrophobicity and limited oral bioavailability. To address these issues, the thin-film hydration method was used to encapsulate quercetin into FQ micelles. Subsequently, 3-aminophenylboronic acid-modified oxidized alginate was crosslinked with polyvinyl alcohol, and simultaneously loaded with glucose oxidase (GOX) and FQ micelles, to construct a glucose-activated cascade acidification-triggered controlled-release hydrogel (OSSP@FQ&GOX). The phenylboronic ester bonds in the hydrogel are responsive to glucose and undergo cleavage. GOX-mediated oxidation of glucose produces gluconic acid, resulting in a lower local pH and subsequently triggering FQ micelle release. The released FQ micelles alleviate oxidative stress and exert immunomodulatory effects, while the hydrogel also provides self-healing, and biocompatible properties that facilitate cutaneous regeneration in diabetic mice. Thus, this study highlights the potential of combining GOX with natural products and multi-stimuli-responsive hydrogels for the treatment of chronic diabetic wounds, while also opening new avenues for the development of multifunctional wound dressings. Full article

Lifespan is increasing throughout the world leading to a rise in non-communicable diseases in the global population that impacts over 800 million individuals with metabolic disorders, such as diabetes mellitus. Metabolic disease presents a significant challenge for clinical care since multi-organ disease progression ensues despite a broad array of treatment protocols. The pursuit of innovative strategies with mammalian forkhead transcription factors of the “O” class (FoxOs) and intimately related pathways of aging, cellular senescence, telomere integrity, oxidative stress, programmed cell death with apoptosis, autophagy, ferroptosis, pyroptosis, and cuproptosis, Wnt/β-catenin signaling, Wnt1 inducible signaling pathway protein 1, and the gut microbiome becomes vital to address the clinical hurdles of metabolic disorders. Platforms incorporating novel diagnostics with artificial intelligence and machine learning can further address the underlying mechanisms tied to FoxOs that include the mechanistic target of rapamycin, AMP activated protein kinase, silent mating type information regulation 2 homolog 1 (S. cerevisiae), and glucagon-like peptide-1 receptor agonists that can markedly influence biological outcomes. Given the premise that it is essential to comprehend the intimate relationship that FoxO signaling pathways hold, FoxOs offer an exciting and promising approach to address the clinical aspects of disease onset, progression, and treatment with metabolic disorders. Full article

Canopy temperature (T_c) is an important indicator for characterizing crop water status and serves as the core variable for constructing the Crop Water Stress Index (CWSI). Timely and accurate diagnosis of crop water stress is of great significance for precision irrigation and yield improvement. Owing to its non-contact and high-efficiency characteristics, unmanned aerial vehicle (UAV) remote sensing has become an effective approach for high-spatiotemporal-resolution monitoring of crop water conditions. However, variations in observation geometry can introduce thermal directional effects in canopy temperature, thereby reducing the stability and reliability of CWSI estimation. In this study, multi-angular thermal infrared imagery acquired by a UAV platform was utilized to investigate the directional characteristics of winter wheat canopy temperature. A kernel-driven model was employed to separate the directional components of canopy temperature and retrieve isotropic temperature parameters that more closely represent the actual thermal status of the crop canopy. Based on these temperature parameters, three CWSI models were constructed and evaluated for crop water stress diagnosis. The results demonstrated that (1) winter wheat canopy temperature exhibited pronounced directional characteristics, and the observed temperature generally decreased with increasing relative azimuth angle between the viewing direction and solar incident direction; (2) after angular correction, the isotropic canopy temperature simulated by the kernel-driven model showed an improved correlation with soil moisture content at a depth of 30 cm (R² = 0.54); and (3) when angular-corrected canopy temperature was used as the input variable for different CWSI models, the sensitivity of all models to crop water variation was substantially enhanced, resulting in improved discrimination among different irrigation treatments. Among the evaluated approaches, the empirical CWSI model achieved the best performance in diagnosing crop water stress variations (R² = 0.73, RMSE = 1.59%). These findings provide a theoretical basis for UAV-based thermal infrared remote sensing of crop water status and offer technical support for precision irrigation management. Full article

Isodon serra is a medicinal plant distributed in the Lingnan region of China. However, I. serra seeds are sensitive to heat, limiting germination in Lingnan’s climate. Seed priming technology provides an effective means to address this problem. Meanwhile, karrikin (KAR) enhances plant growth and stress tolerance, but its mechanism in I. serra remains unclear. Therefore, in this study, different KAR concentrations were selected for priming to examine the phenotypic and physiological responses, and multi-omics analysis was used to explore the molecular mechanism of promoted germination under heat stress. The optimal concentration of 0.05 µmol/L KAR raised the seed germination rate under heat stress. This priming treatment reduced membrane damage, indicated by lower malondialdehyde (MDA) levels and relative electrical conductivity (REC) and oxidative stress, by regulating antioxidant enzymes and increasing glutathione (GSH) content. Multispectral phenotyping revealed distinct spectral features at 880 nm and 970 nm in primed seeds, correlating with enhanced vigor. Integrated multi-omics analysis demonstrated that the alleviation of heat stress was primarily mediated through the glutathione metabolism pathway, with key roles played by genes such as cluster-23509.3, cluster-15076.0, and cluster-22471.0. In summary, KAR priming enhances osmotic adjustment, improves reactive oxygen species (ROS)-scavenging enzyme activities, and regulates glutathione metabolism to mitigate heat stress in I. serra. These findings provide valuable insights for optimizing the cultivation and management of I. serra under heat stress conditions. Full article

Background: Skin photoaging, primarily induced by chronic ultraviolet (UV) radiation exposure, is characterized by dryness, wrinkle formation, pigmentation abnormalities, and reduced skin elasticity, resulting from oxidative stress, inflammation, and degradation of the extracellular matrix. Codonopsis pilosula, a traditional food–medicine homologous plant, is recognized for its anti-aging properties. However, its lipophilic components (designated as CP-L) remain insufficiently explored. Methods: Herein, we developed a thermosensitive nanogel encapsulating CP-L-loaded transferosomes (CP-L nanogel) to enhance topical delivery and evaluated its effects in both a UV-induced photoaging mouse model and UVB-irradiated HaCaT keratinocytes. Results: In UV-induced mice, topical application of the nanogel markedly reduced skin wrinkling and epidermal hyperplasia, with epidermal thickness decreased by 83.2% compared to the model group (p < 0.01), and restored skin elasticity and collagen deposition, as evidenced by a 35.5% increase in collagen area fraction (p < 0.01). Correspondingly, in UVB-irradiated HaCaT cells, it significantly increased cell viability from 53.0 ± 9.6% to 89.4 ± 1.0% (p < 0.01) and suppressed apoptosis from 30.1 ± 0.48% to 12.4 ± 0.66% (p < 0.01). Furthermore, the CP-L nanogel consistently attenuated oxidative stress, with SOD, CAT, and GSH-Px activities increased by 73.1%, 188.1%, and 18.2%, respectively (p < 0.01), and MDA levels reduced by 71.0% (p < 0.01), while inflammatory responses were suppressed, as TNF-α, IL-1α, IL-1β, and IL-6 levels decreased by 28.3%, 22.6%, 12.8% and 31.9%, respectively (p < 0.01). Mechanistically, transcriptomic and molecular analyses revealed that the nanogel potently inhibited the UV-induced activation of the FGFR/PI3K/AKT/mTOR/p70S6K signaling cascade at both transcriptional and protein levels, with the phosphorylation levels of FGFR, PI3K, AKT, mTOR, and p70S6K significantly reduced by 43.9%, 30.9%, 38.8%, 34.9%, and 57.3%, respectively (p < 0.01). Molecular docking and dynamics simulations identified isofuranodienone and aromadendrene oxide-(2) as key constituents with high-affinity, stable binding to FGFR1 and AKT1. The cytoprotective effect of the nanogel was completely abolished by co-treatment with the FGFR inhibitor PD173074, confirming functional reliance on this pathway. Enhanced cellular delivery of the formulation was directly demonstrated by flow cytometry, showing an approximately 1.8-fold increase in cellular uptake compared to the free drug (p < 0.01). Conclusions: Collectively, these results demonstrated that the CP-L nanogel alleviated skin photoaging through a multi-faceted mechanism involving enhanced cellular delivery, potent antioxidant and anti-inflammatory activities, and specific inhibition of the FGFR/PI3K/AKT/mTOR signaling cascade, highlighting its potential as a multitargeted topical agent derived from an edible plant. Full article

Problematic subgrade soils degrade pavement performance, while conventional cement/lime stabilizers generate excessive carbon emissions. Unlike earlier reviews that focus on single-material systems—such as industrial by-products, alkali-activated binders for expansive soils, or geopolymers for pavement applications—an integrated framework spanning reaction mechanisms, microstructural evolution, engineering parameterization, and life-cycle validation is proposed The work offers three distinctive contributions: (i) a four-level evidence chain hierarchy (strength → microstructure → durability → leaching/LCA) to grade research completeness; (ii) repositioning resilient modulus, permanent deformation, and pore-connectivity evolution as core engineering outputs bridging material design and structural response; and (iii) a comparative assessment of alkali-activated geopolymers, low-clinker calcium-based composites, and multi-scale reinforcement strategies under consistent durability and environmental boundaries. Quantitative synthesis reveals the following: strength retention after 12 wet–dry/freeze–thaw cycles ranges from 60% to 85%; resilient modulus improvements over untreated soils reach 30%–120%, yet stress-dependent characterization remains essential; leaching concentrations of hazardous elements (Cr, Ba, Pb) can increase by 50%–200% after durability cycling if pore connectivity rebounds. Life-cycle carbon comparisons are boundary-sensitive—geopolymer advantages shrink from 60% to ≤20% when activator transport and pre-treatment are included. We conclude that the primary barrier to engineering adoption is not the absence of high-strength formulations, but the lack of extrapolatable design parameters and closed-loop evidence chains. A decision-support framework incorporating durability retention, leaching safety, carbon footprint, and field validation is proposed to guide robust design and industrial scaling. Critically, the review identifies that engineering adoption is constrained not by the absence of high-strength formulations, but by the lack of standardized construction protocols, quality control procedures, and long-term field performance data—gaps that must be addressed through coordinated field-scale demonstration projects. Full article

Cancer development arises from dynamic interactions between inherited susceptibility and modifiable environmental exposures, among which diet plays a central role. Carotenoids, lipophilic plant-derived pigments including lycopene, α-carotene, and β-carotene, and retinoids, the vitamin A derivatives that regulate gene transcription via retinoic acid receptors (RARs) and retinoid X receptors (RXRs), have been extensively investigated for their chemopreventive and therapeutic potential. This review aims to provide an integrated, mechanism-based synthesis of the roles of lycopene, α- and β-carotene, and retinoids in cancer chemoprevention and to clarify the conditions under which they are most likely to be effective. Beyond summarizing established antioxidant and nuclear-receptor mechanisms, we highlight as a novel emphasis the epigenetic actions of these compounds, including effects on DNA methylation, histone modification, and microRNA regulation, and we integrate these with the well-recognized divergence between dietary and high-dose supplement outcomes. Experimental evidence demonstrates that carotenoids modulate oxidative stress, inflammation, proliferation, apoptosis, angiogenesis, and metastasis through pathways such as Nrf2/ARE, NF-κB, STAT3, Akt/mTOR, MAPK, and Wnt/β-catenin. Lycopene, in particular, exhibits strong antioxidant capacity and multi-target signaling effects, while provitamin A carotenoids additionally influence retinoid-mediated transcriptional programs. Retinoids exert broader differentiation-inducing and antiproliferative effects through direct nuclear receptor signaling and represent one of the few successful differentiation therapies in oncology, most notably in acute promyelocytic leukemia. Epidemiologic studies generally associate higher dietary carotenoid intake with reduced risk of several malignancies, including prostate, breast, lung, colorectal, and gastric cancers. However, randomized trials of isolated high-dose supplementation, particularly β-carotene in smokers, have demonstrated null or harmful effects, highlighting a critical divergence between whole-food dietary patterns and pharmacologic supplementation. In conclusion, carotenoids and retinoids possess biologically plausible anticancer properties, yet their clinical utility remains context dependent. Future research should prioritize biomarker-guided, precision-based strategies, standardized formulations, and whole-food dietary approaches to clarify their role in cancer prevention and treatment. Full article

Genomic instability is a defining feature of cancer progression and therapeutic resistance, yet contemporary oncology interprets it largely through tumor-intrinsic genetic alterations, with less attention to the evolving host physiological context in which DNA damage accumulates and genome maintenance operates. In this perspective, we propose a longitudinal host-transfer-state framework that treats host physiology not as a static background but as a continuously evolving adaptive system. Gut microbial ecology, micronutrient physiology, inflammatory signaling, circadian organization, hydration, environmental exposures, and chronic stress are framed as interacting biologic transfer systems that shape DNA repair fidelity, oxidative buffering, immune coordination, and adaptive tumor behavior over time. These influences are proposed to vary by tumor type, treatment context, and individual physiologic reserve, and clinically observable disease may lag behind deeper latent biologic dynamics. We further outline how longitudinal multi-omic integration and constrained, bounded artificial intelligence—used for longitudinal data integration, normalization, contextualization, and bounded analytical support rather than autonomous decision-making—could identify patient-specific constraints on genome maintenance and treatment tolerance. Host-directed strategies are presented as complementary to, not replacements for, established tumor-directed therapies. Full article

The aim of this study was to examine the hepatoprotective activity of multicomponent mixtures of natural origin in the BALB/C mouse model (n = 59), with acute direct toxic liver injury (DTLI) induced by the administration of streptozotocin (STZ) (100 mg/kg) in combination with a high-fat and high-fructose diet (HFFD). The hepatoprotective activity of activated hydrolytic lignin (Bp-Cx-1), methanolic fraction of Bp-Cx-1 (Bp-Cx-M) and isoflavones from kudzu Pueraria lobata roots (IFL) were evaluated on molecular level using mass spectrometry (MS)-based omics technologies. Untargeted label-free DIA quantitation resulted in 7214 protein groups identification (FDR 1%) after filtering across 40 liver tissue extracts. All treatment groups were closer to the control samples on the liver proteomic landscape compared to the untreated DTLI group, with the best results shown for the Bp-Cx-M and IFL groups. In order to identify differences between specific groups, we applied the post hoc Dunn’s test and used Hedges’ g as the effect size metric, revealing 64 proteins that tended to return to their normal level after treatment. In-depth proteomic liver tissue analysis enabled us not only to reveal the main pathways such as inflammation and oxidative stress, which are in a good agreement with DTLI and non-alcoholic liver disease pathophysiology, but also to evaluate hepatoprotective activity of multicomponent mixtures of natural origin containing polyphenols and mostly associated with protein metabolism (e.g., PSMD7, HCFC1) and deubiquitination pathways (e.g., UCHL3). It is worth noting that the Bp-Cx-1 isolated methanol fraction (Bp-Cx-M) demonstrated a pronounced increased hepatoprotective activity compared to the parent material due to the enrichment with active components such as polyphenols. Consistent with the proteomic findings of restored ubiquitin–proteasome function, assessment by comet assay revealed that treatments with Bp-Cx-M and IFL significantly reduced DNA damage by 50% compared to the untreated DTLI group. The developed MS-based multi-omics approach may be implemented for the robust and high-throughput screening method during assessment of new hepatoprotective agents of synthetic or natural origin. Full article

Objectives: Aspidopterys obcordata has been traditionally used by the Dai people in Xishuangbanna, China, for the prevention and treatment of renal calculi. This study aimed to investigate the inhibitory effect of A. tomentosa extracts on calcium oxalate stone formation. Methods: The extracts of A. tomentosa (EA) were obtained via 95% ethanol reflux extraction, followed by multi-polar solvent extraction and elution. The HK-2 cell injury model induced by calcium oxalate and the renal calculus mouse model established by intraperitoneal injection of glyoxylic acid were established to assess drug efficacy. EA intervention was performed to evaluate its effects on calcium oxalate crystal deposition, renal tubular injury, cell apoptosis, and serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Furthermore, the potential mechanism underlying, particularly the regulation of PERK/ATF4/CHOP signaling pathway and endoplasmic reticulum stress-mediated apoptosis, was investigated. Results: EA treatment significantly reduced renal calcium oxalate crystal deposition, alleviated renal tubular injury, inhibited cell apoptosis, and decreased Scr and BUN levels. Mechanistically, the protective effects of EA were mediated by the downregulation of the PERK/ATF4/CHOP signaling pathway and the suppression of endoplasmic reticulum stress-mediated apoptosis. Conclusions: These findings provide experimental evidence supporting that A. tomentosa can be developed as a promising agent for the prevention of nephrolithiasis. Full article

Major depressive disorder (MDD) is a prevalent psychiatric disorder in which epigenetic mechanisms, particularly DNA methylation (DNAm), may contribute to disease vulnerability and treatment response. Epigenome-wide association studies (EWAS) have increasingly investigated longitudinal methylomic changes associated with therapeutic interventions in depression; however, methodological heterogeneity limits comparability across studies. This critical review examined the methodologies and findings of longitudinal EWAS evaluating DNAm changes related to treatment response in MDD and treatment-resistant depression (TRD). A literature search identified seven studies published up to 20 June 2026. Six studies investigated non-pharmacological interventions, including electroconvulsive therapy, trauma-focused psychotherapy, and cognitive interventions, and one study explored pharmacotherapy. Considerable heterogeneity was observed regarding sample size, biospecimen type, methylation platforms, preprocessing pipelines, covariate adjustment, statistical modeling, and longitudinal sampling schedules. Most studies used Illumina EPIC array-based workflows and mixed-model analytical approaches, while one study employed sequencing-based methylation profiling. Overall, treatment-related methylation changes were modest and often limited to specific CpG sites or differentially methylated regions associated with immune, inflammatory, stress-related, and neurobiological pathways. Current evidence supports the feasibility of longitudinal EWAS approaches in depression research but highlights the need for larger cohorts, methodological standardization, and integration with multi-omics and clinical data to improve reproducibility and biomarker discovery. Full article