Search Results (2,369)

Iron, with the unique stability of its nucleus, occupies an unusual position among the elements: its abundance on Earth is not simply a geological accident but a direct consequence of nuclear reactions that happened inside stars billions of years ago. Formed at the final stages of fusion in stars, iron spread through space by supernova explosions and became part of the material that formed Earth, eventually becoming the dominant component of the planet’s core. At the surface, iron’s redox chemistry shaped the early atmosphere and oceans, and its availability as a soluble ferrous ion in the anaerobic Archean ocean made it a natural cofactor for the first enzymatic reactions. That same redox flexibility and the ability of iron to shuttle between Fe²⁺ and Fe³⁺ across a wide range of electrochemical potentials explain why virtually every major metabolic pathway in biology depends on iron in one form or another. Yet iron is also dangerous: free and chelated iron can catalyze the production of toxic hydroxyl radicals through Fenton chemistry, the reactivity of which depends strongly on the nature of the chelating ligand, and every living system must balance its need for iron against the oxidative damage that uncontrolled iron causes. This tension between catalytic necessity and chemical toxicity has driven much of the regulatory complexity we observe in modern iron metabolism. In this review, we first outline iron’s journey from its formation in stars to its role in shaping Earth’s structure and the emergence of early iron-dependent biology. We then discuss in detail how fundamental physical and chemical factors continue to influence living systems. Full article

Secondary fermentation is a critical stage in the production of traditional method sparkling wines, during which yeast metabolism drives major changes in wine composition. However, the biochemical processes occurring during this phase and the influence of bottle closure systems remain poorly understood. This study evaluated the evolution of basic oenological parameters, free amino acids and volatile compounds during the first 90 days of secondary fermentation under two bottle closure systems: crown cap and tirage-cork. Fermentation time was the principal factor governing wine composition, with the most pronounced metabolic changes occurring between 30 and 45 days after bottling. Active nitrogen metabolism was evidenced by substantial amino acid redistribution, particularly involving ASN, ORN, AAA, GLU and ASP, while the accumulation of higher alcohols and other fermentation-derived volatiles reflected intense yeast metabolic activity during bottle fermentation. Although both closure systems successfully completed fermentation, tirage-cork-fermented wines showed a tendency towards faster fermentation progression and distinct patterns of amino acid and volatile compound development. Pearson correlation analysis revealed generally weak to moderate associations between amino acids and their corresponding volatile compounds, supporting the view that aroma formation results from the integration of multiple metabolic processes rather than from precursor availability alone. Overall, the results suggest that closure-associated metabolic divergence becomes detectable during the active phase of secondary fermentation and may contribute to differences in nitrogenous and aroma-related compounds. These findings suggest that bottle closure may represent an important technological variable associated with differences in the metabolic and compositional trajectories observed during the active phase of secondary fermentation. Given the limited biological replication of the present study, these observations should be interpreted with caution and warrant confirmation through studies incorporating biological replication and direct measurements of oxygen transfer. Full article

In spite of at least six discrete classes of drugs available for cancer treatment, the quest for more biologic drugs continues. One type of biologic molecule that occurs naturally in the body is microRNA. MicroRNAs regulate post-transcriptional gene expression and can be under expressed in cancer (tumor suppressor microRNAs) or over expressed (oncogenic microRNAs). Strand-specific mimics of microRNAs have been developed and used successfully in vitro, in vivo, and in clinical trials, to control multiple aspects of cancer including metastasis, apoptosis and proliferation. Each microRNA is capable of binding a specific target mRNA or mRNAs, sometimes simultaneously interfering with multiple genes in a single pathway, or binding with a single nodal mRNA. Some microRNAs can facilitate chemotherapy that has stopped working, addressing the issue of drug resistance. Without chemical modification, microRNAs are too vulnerable to have lasting therapeutic value. Chemical modifications to microRNAs have provided nuclease resistance and greater stability and are the basis for microRNA mimics that can be used therapeutically. However, without a vehicle, microRNA mimics do not cross cell membranes. These nanoparticles can cause inflammatory reactions in patients. Additional modifications that enabled microRNA mimics to cross cell membranes include substituting uracil with 5-fluorouracil. Lessons from an siRNA therapeutic called Patisiran offer a roadmap for future success for microRNAs in cancer. This review provides a historical perspective of the continuing evolution of microRNA mimics for cancer treatment. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has traditionally been conceptualized as a predominantly metabolic disorder driven by obesity and insulin resistance. However, recent advances in human genetics have revealed a more complex picture that encompasses germline susceptibility variants, protective loss-of-function alleles, polygenic risk models, and somatic clonal evolution. Since the discovery of PNPLA3 (patatin-like phospholipase domain-containing 3) I148M, multiple loci—including TM6SF2, MBOAT7, GCKR, HSD17B13, MTARC1, GPAM, and CIDEB—have substantially expanded the mechanistic understanding of disease heterogeneity and hepatocellular vulnerability. Recent studies integrating partitioned polygenic risk scores and unsupervised phenotypic clustering suggest that MASLD may be organized into at least two predominant subtypes: a liver-specific subtype characterized by intrinsic hepatocellular susceptibility, and a cardiometabolic subtype associated with systemic metabolic dysfunction and increased cardiovascular risk. Analyses of cirrhotic liver tissue have, in turn, demonstrated somatic clonal expansion of hepatocytes harboring adaptive metabolic mutations, adding an evolutionary dimension to advanced disease. On this basis, we propose an integrated LS/CM/C framework encompassing liver-specific (LS), cardiometabolic (CM), and clonal (C) components. This model offers a conceptual structure that links germline genetics, metabolic heterogeneity, somatic adaptation, and emerging pharmacogenomic strategies. The recent development of genotype-directed therapies targeting PNPLA3 and HSD17B13, together with the approval of resmetirom and semaglutide, further supports the transition toward biologically stratified hepatology. Although prospective validation remains necessary, the convergence of genetics, clonal biology, and targeted therapeutics suggests that MASLD is moving toward an era of precision medicine. Full article

To understand the adaptive evolution of endangered plateau freshwater fishes to environmental stress and to better explore the underlying mechanisms in Aspiorhynchus laticeps—a critically endangered fish endemic to the Tarim Basin, Xinjiang, China—a combination of ecological experiments and transcriptome sequencing (RNA-seq) technology was used to study the differences in gene expression patterns among individuals under different salinities and flow conditions. This experiment included four treatment groups (CON, H-SA-S, L-SA, L-SA-S). A. laticeps specimens with an average weight of 2.92 ± 0.62 g and a body length of 58.22 ± 5.10 mm were selected, with three biological replicates for a 96 h combined stress treatment. Moreover, the relationships between these differences and the aquatic environment were analyzed. A total of 1847 differentially expressed genes (DEGs), including 935 upregulated genes and 912 downregulated genes, were identified under different aquatic environment stress modes. GO and KEGG enrichment analyses revealed that TNF signal transduction, the NF-κB pathway, and metabolic regulation were significantly enriched among the DEGs (p < 0.05). High salinity–alkali stress significantly activates the TNF/NF-κB pathway, regulates MST1, LOC107702867, LOC113110979 and other genes to enhance the body’s resistance; water flow changes mainly regulate energy metabolism through genes such as NEHOM01_1600 and gptl. These findings provide an important scientific basis for the ecological adaptability, protection, and proliferation of endemic and endangered fish in China, as well as for germplasm innovation to address ecological deterioration in plateau fishes in alpine and arid areas. This study provides a molecular-level theoretical foundation for artificial habitat regulation and the conservation of endangered Aspiorhynchus laticeps populations in the Tarim River. Full article

In this study, pure hydroxyapatite (HAp) was successfully produced by using eggshells. The eggshells were collected locally and calcined to get CaO from them. The CaO powder was reacted with diammonium hydrogen phosphate in a mechanochemical method using attritor milling. A portion of the synthesized samples was subjected to a second calcination process at 900 °C to investigate the thermal effects on the material. The structures of the samples were investigated by scanning electron microscopy, X-ray diffraction, and infrared spectroscopy. The as-prepared HAp appeared to be nanocrystalline with low-intensity reflections, which transformed into a highly crystalline hexagonal phase after heat treatment, as revealed by XRD analysis. Quantitative analysis revealed the thermal evolution of the secondary Ca(OH)₂ phase, due to the thermal decomposition into CaO without causing HAp decomposition into tricalcium phosphates. FTIR analysis showed characteristic phosphate bands for both samples, but the calcined sample displayed sharper peaks and a clear loss of residual water and carbonates. SEM observations also highlighted the major morphological transformation. The highly aggregated as-prepared nanoparticles formed larger, well-defined grains. Notably, the calcined sample also exhibited a rough, textured surface with a macroporous network with interconnected channels. EDS analysis confirmed a Ca-P-O-rich composition, where the elevated Ca/P ratio (Ca/P = 2.28) suggested the presence of secondary calcium-rich phases. These structural, chemical, and morphological characteristics suggest that eggshell-derived HAp, with or without a second heat treatment, has high potential and may be optimized for different applications in bone tissue engineering. However, biological performance was not evaluated in this study. Full article

Radiotherapy is a cornerstone of breast cancer treatment, but its efficacy is frequently limited by intrinsic and acquired radioresistance as well as dose-limiting toxicity to surrounding normal tissues. Nanoparticle-mediated radiosensitization has emerged as a promising strategy to enhance the therapeutic index of irradiation by combining physical dose amplification with biological, microenvironmental, and immunological modulation. In this systematic review, we evaluated preclinical evidence on nanoparticle-mediated radiosensitization in breast cancer, with emphasis on nanoplatform design, mechanistic patterns, therapeutic efficacy, and translational relevance. A total of 66 studies published between 2015 and 2026 were included. The identified systems encompassed a broad range of materials, including gold-, silver-, platinum-, bismuth-, gadolinium-, polymer-, lipid-, and hybrid-based nanoplatforms, frequently incorporating targeting ligands, catalytic components, biomimetic coatings, or therapeutic payloads. Enhanced radiation responses were most commonly associated with high-atomic-number (high-Z)-mediated energy deposition, increased reactive oxygen species generation, and enhanced DNA damage persistence. Additional mechanisms, including redox modulation, hypoxia targeting, regulated cell death, and immune activation, reflect the evolution of nanoparticle-assisted radiotherapy from predominantly physical radioenhancement toward multifunctional physicobiological strategies. Triple-negative breast cancer models predominated throughout the literature. Across preclinical models, nanoparticle-assisted irradiation consistently improved clonogenic survival, tumor control, and, in selected studies, survival. However, substantial heterogeneity in study design and limited use of rigorous radiobiological endpoints restricted cross-study comparability. The available preclinical evidence indicates that the most promising nanoparticle-mediated radiosensitization strategies integrate physical dose enhancement with biologically active mechanisms targeting oxidative stress, hypoxia, persistent DNA damage, immune signaling, and tumor microenvironmental resistance. Collectively, these findings suggest that the field is evolving from predominantly physical radioenhancement toward multifunctional, mechanism-driven physicobiological strategies. However, clinical translation remains constrained by methodological heterogeneity and limited radiobiological validation, highlighting the need for standardized preclinical evaluation and clinically feasible nanoplatforms tailored to subtype-specific mechanisms of radioresistance. Full article

Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker in multiple myeloma (MM), providing dynamic insight into tumor burden, clonal evolution and molecular heterogeneity. Unlike conventional bone marrow-based diagnostics, ctDNA analysis offers a systemic approach to disease assessment and may better reflect spatially heterogeneous and extramedullary disease. Recent advances in highly sensitive molecular techniques, including digital droplet polymerase chain reaction and next-generation sequencing, have improved the feasibility of ctDNA detection and longitudinal disease monitoring in MM. Increasing evidence demonstrates substantial concordance between ctDNA and bone marrow genomic profiles, while also highlighting the ability of ctDNA to identify resistant subclones, molecular relapse and genomic evolution during therapy. ctDNA has shown potential clinical utility in molecular profiling, therapeutic monitoring and minimal residual disease assessment. ctDNA may become increasingly relevant in the era of novel immunotherapies, including chimeric antigen receptor T-cell therapy and bispecific antibodies. Despite these promising applications, several biological and technical limitations still restrict routine clinical implementation, including low ctDNA concentration in patients with minimal disease burden and lack of methodological standardization. Overall, ctDNA represents a rapidly evolving tool with significant potential to improve personalized disease monitoring and therapeutic strategies in MM. Full article

Cardiomyopathies have traditionally been regarded as disorders driven primarily by cardiomyocyte injury resulting from genetic defects, infection, metabolic stress, or toxic exposure. This paradigm has substantially advanced diagnosis and treatment. Still, it does not fully account for the marked heterogeneity in disease progression, persistent fibrosis, or variable therapeutic responses among patients with similar phenotypes. Increasing evidence indicates that immune remodeling is not merely a secondary consequence of myocardial injury but a dynamic process that actively shapes disease evolution. In this review, we integrate recent advances in cardiovascular immunology, single-cell and spatial transcriptomics, immunometabolism, and systems biology to propose a unified framework of immunological reprogramming in cardiomyopathies. We discuss how danger-associated molecular patterns, inflammasome activation, trained immunity, the cGAS–STING pathway, fibroblast–immune interactions, and the cardio–bone marrow axis converge to establish chronic inflammatory circuits that promote fibrosis, electrical remodeling, and progressive ventricular dysfunction. We further examine the emerging concept of immunotypes, emphasizing that distinct immune programs may underlie the biological heterogeneity of cardiomyopathies beyond conventional phenotypic or genetic classification. Finally, we discuss the translational potential of immune profiling, advancing a shift toward viewing cardiomyopathies as disorders of a dysregulated cardiac immune ecosystem. We propose that immune ecosystem organization constitutes an additional biological dimension that complements traditional phenotypic and genetic classifications of cardiomyopathies. Full article

Mumps virus (MuV) genotype G is widely represented among circulating strains, but the evolutionary patterns of the hemagglutinin–neuraminidase (HN) gene remain incompletely understood. In this study, we analyzed publicly available full-length genotype G HN sequences using phylogenetic, phylodynamic, codon-based selection, and structure-guided epitope prediction approaches. The genotype G HN sequences were categorized into Clade 1, an operationally defined Diverse group, and Clade 2. Clade 1, which was composed mainly of Japanese strains, showed a relatively structured pattern over time. In contrast, Clade 2 showed more recent diversification and an overall increase in relative genetic diversity, although this phylodynamic pattern was sensitive to sampling structure. The Diverse group was phylogenetically heterogeneous, and its Bayesian skyline estimates were not used for biological interpretation because repeated analyses showed unstable posterior behavior. Root-to-tip regression supported temporal structure in the complete dataset, with the strongest signal in Clade 2. Bayesian molecular dating estimated the time to the most recent common ancestor of the sampled genotype G HN sequences at approximately 1932, and the mean evolutionary rate was 4.925 × 10⁻⁴ substitutions/site/year. Although the HN protein is a major surface antigen and a target of neutralizing antibodies, codon-based analyses showed no robust evidence of positive selection using multiple methods. Instead, many codon sites were inferred to be under purifying selection, suggesting that genotype G HN evolution is largely constrained by the need to maintain protein function. Predicted B-cell epitope regions were broadly similar among representative genotype G strains. Overall, these findings indicate that genotype G HN lineages have followed distinct evolutionary patterns, while the HN gene remains mainly shaped by purifying selection. These findings may help improve our understanding of MuV genotype G HN gene evolution and support future molecular surveillance. Full article

Respiratory medicine is transitioning from symptom-driven, standardized care to a more precise, patient-specific approach guided by molecular profiling. This evolution is being enabled by advances in liquid biopsy, multiomics, and artificial intelligence (AI) analytics. Fractional exhaled nitric oxide (FeNO) and blood eosinophils, the two commonly used markers in asthma, are now being joined by more precise airway markers such as galectin-10, which could aid clinicians in making more informed decisions for biological treatments. In chronic obstructive pulmonary disease (COPD) similar progress is underway, with treatment now emphasizing inflammation endotypes, especially eosinophilic patterns, to direct therapeutic choices. Alongside these developments, routine blood-based ratios (e.g., platelet-to-lymphocyte and neutrophil-to-lymphocyte) are being explored as predictors of exacerbation risk, and forced oscillation testing (FOT) is proving useful for picking up early disease shifts. In more severe conditions, biomarkers are linked to an early and better prognosis, enabling timely intervention. Markers like Matrix metalloproteinase-7 (MMP-7) and CC chemokine ligand 18 (CCL18) have proven to be reliable indicators of mortality and disease progression in idiopathic pulmonary fibrosis. Meanwhile, in lung cancer, liquid biopsies, especially those measuring circulating tumor DNA and micro-RNA (miRNA) panels, are enhancing screening accuracy while helping to cut down on the high false-positive rates seen with low-dose computerised tomography (CT). Other respiratory conditions such as bronchiectasis, pulmonary embolism, pneumonia, and acute respiratory distress syndrome (ARDS) are also benefiting from biomarker advances. At the same time there is a growing push to standardize how these biomarkers are measured. AI-based clinical decision support systems are also playing an increasingly important role in the translation of all these complicated data into actionable clinical insights. Together these developments pave the way for improved respiratory care that is precise and responsive to individual patient needs. Full article

Background/Objectives: Breast cancer (BC) remains the most frequently diagnosed malignancy among women worldwide, and patient outcome is strongly influenced by disease stage at diagnosis. Although imaging-based screening has improved early detection, its performance may be reduced in dense breast tissue and is associated with false-positive findings. In addition, tissue biopsy is invasive and unsuitable for longitudinal disease monitoring. Liquid biopsy (LB) has emerged as a minimally invasive approach for detecting tumor-derived material in peripheral blood. However, early-stage tumors typically exhibit low tumor burden and limited biomarker shedding, generating weak systemic signals that challenge reliable detection. This review examines current and emerging LB biomarkers for early BC detection. Methods: A comprehensive review of recent literature was conducted focusing on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), circulating RNAs, proteins, and other blood-based biomarkers associated with early BC. Studies addressing biomarker biology, detection technologies, clinical applications, and methodological limitations were critically evaluated. Results: ctDNA, CTCs, EVs, circulating RNAs, proteins, and additional blood-based biomarkers capture distinct aspects of tumor biology and disease evolution. ctDNA enables the analysis of tumor-specific mutations, methylation patterns, and fragmentation profiles, whereas CTCs provide direct cellular and phenotypic information despite their rarity and marked epithelial–mesenchymal plasticity. EVs offer increased molecular stability and actively participate in tumor progression, immune modulation, and metastatic niche formation. Nevertheless, low biomarker abundance, biological heterogeneity, technical variability, and background biological noise continue to limit analytical performance, particularly in early-stage disease. Current evidence further suggests that no single biomarker consistently provides sufficient sensitivity and specificity for reliable early BC detection. Conclusions: LB represents a promising strategy for non-invasive early BC detection. Future clinical implementation will likely depend on integrated multi-analyte approaches that combine complementary genomic, transcriptomic, proteomic, and cellular information, supported by multi-omics technologies and artificial intelligence-based analytical frameworks. Full article

Invasive candidiasis, predominantly driven by multidrug-resistant Candida species and intractable biofilms, represents an escalating global health crisis with mortality rates rivaling major infectious diseases. The clinical efficacy of conventional antifungal agents—azoles, polyenes, and echinocandins—is severely compromised by poor tissue penetration, dose-limiting systemic toxicity, and the rapid evolution of complex resistance mechanisms. Here, we review the two-decade structural evolution of nanotechnological interventions designed to overcome these pharmacological and biological barriers. We systematically analyze advanced nanosystems, including lipid-based formulations, natural polymers, and biogenic metallic nanostructures, highlighting their capacity to penetrate the dense extracellular polymeric substance (EPS), combat potential fungal ‘nano-resistance’, and significantly reduce metabolically dormant persister cell populations. The literature search was performed using the electronic databases PubMed, Scopus, Web of Science, and Google Scholar. Publications indexed between 2015 and 2025 were primarily considered, while seminal studies published before 2015 were included when necessary to provide historical context and foundational knowledge. We place specific emphasis on next-generation biomimetic and exosome-inspired nanocarriers, which significantly reduce systemic host toxicity while maximizing targeted antifungal efficacy. In this context, the synergistic integration of smart nanocarriers to actively disassemble fungal resistance networks, such as the target of rapamycin (TOR) signaling pathway and sphingolipid biosynthesis. Finally, we outline a strategic roadmap to bridge the translational “Valley of Death”. By prioritizing manufacturing standardization, comprehensive long-term biosecurity profiling, and rationally designed biomimetic platforms, we propose an alternative way to outpace the evolutionary adaptations of fungal pathogenesis and translate these innovations into the clinic. Full article

Extracellular vesicles have emerged as promising cell-free therapeutic agents for wound healing due to their remarkable ability to modulate inflammatory responses, promote angiogenesis, and enhance tissue regeneration. These biological nanocarriers deliver bioactive cargo, including regulatory miRNAs, proteins, and lipids, to recipient cells, thereby modulating key signaling pathways governing tissue repair. However, the clinical translation of extracellular vesicle (EV)-based therapies is substantially limited by challenges in delivery efficiency. Local drug delivery systems (LDDSs) offer several key advantages, including reduced clearance by the reticuloendothelial system, enhanced biodistribution to wound sites, prolonged local residence time, and precise spatial targeting of therapeutic effects. This review systematically summarizes recent advances in EV-based therapies for wound repair, with a particular focus on in situ forming and implantable LDDSs, such as stimuli-responsive hydrogels. We comprehensively discuss the molecular and cellular mechanisms through which EVs facilitate healing across all phases of wound repair. Furthermore, we critically evaluate the evolution of these delivery platforms, transitioning from conventional passive-release systems to advanced stimuli-responsive hydrogels and microneedle systems, assessing their design rationale and integration with EV biology. We also address key translational challenges and opportunities: scalable manufacturing, standardized quality control, and regulatory pathways, offering a forward-looking view on clinical implementation of EV-LDDS hybrids in precision regenerative therapy. Full article

The omics sciences represent a revolution for clinical studies, offering integrative approaches to analyzing biological data with unprecedented depth. From the discovery of the double-helix structure of DNA to the CRISPR-Cas9 gene editing tool, passing through the evolution of sequencing platforms and the exponential advance of computing power and in silico tools, omics has progressed in its role of leading innovative solutions for old challenges in health sciences. In this review, we describe different omics, the history of their techniques and technologies, data analysis and up-to-date visualization tools used for clinical data in research and health systems. We also discuss how omics are currently being applied in diagnosis, precision and personalized medicine. For the future, omics vow to underpin the majority of decisions made by health professionals, allowing individualized treatments based on Big Data and personal biological information. Full article