Search Results (659)

Keratoconus, a progressive corneal ectasia, remains a major cause of irreversible visual impairment worldwide. Conventional corneal cross-linking (CXL) with riboflavin/ultraviolet A (UVA) has revolutionized clinical management, yet its efficacy is still constrained by epithelial barriers, oxygen dependence, and safety concerns in thin corneas. Emerging nanotechnology provides a transformative opportunity to overcome these bottlenecks. This review highlights the enhancement of riboflavin delivery efficiency by nanocarriers, the photodynamic optimization of nano-enhanced cross-linking agents, and the synergistic strengthening effect of nanocomposites on corneal mechanical strength. We emphasize not only their potential to enhance drug penetration, improve cross-linking efficiency, and extend clinical indications, but also their role in advancing toward a new generation of personalized, intelligent, and minimally invasive corneal therapy. Finally, we discuss translational challenges, including manufacturing, long-term biosafety, and regulatory frameworks, and present a theoretical roadmap that integrates nanotechnology, real-time imaging, and artificial intelligence (AI)-assisted decision-making to achieve a closed-loop “sense–decide–act” therapeutic system. By situating nanomaterial-enhanced CXL within precision ophthalmology, this review highlights its capacity to redefine the standard of care for keratoconus and related ectatic disorders. Full article

Over the last years, incretin receptor agonists—including glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide—have dramatically improved the management of type 2 diabetes, overweight and obesity. However, as the use of incretin receptor agonists continues to increase worldwide, micronutrient deficiencies—including iron deficiency—have emerged as newly recognized adverse effects of these drugs. The present article aims to discuss recent preliminary observational evidence on the potential relationship between incretin receptor agonist-based therapies and the development of iron deficiency and iron deficiency anemia (IDA), as well as the potential mechanisms by which incretin receptor agonists may affect iron homeostasis. Potential mechanisms and factors underlying the development of iron deficiency and IDA in patients treated with incretin receptor agonist-based therapies include inadequate dietary iron intake (due to incretin receptor agonist-mediated reduction in food intake and/or gastrointestinal adverse effects of incretin receptor agonists), low dietary variety, monotonous diets, and changes in food preferences, as well as impairment of intestinal iron absorption (due to delayed gastric emptying, reduced small intestinal motility and/or decreased gastric acid secretion caused by incretin receptor agonists). Moreover, vitamin B2 (riboflavin) deficiency and changes in gut microbiota composition are hypothetical mechanisms that may partly explain iron deficiency in patients treated with incretin receptor agonists, although these hypotheses require confirmation through mechanistic studies. Even though iron deficiency and IDA currently appear to be uncommon adverse effects of incretin receptor agonist-based therapies, clinicians should be aware of the possibility of their occurrence to ensure appropriate prevention and management of these nutritional complications. Nevertheless, future prospective studies are certainly needed to better establish the causal relationship between the initiation of incretin receptor agonist-based therapies and the development of iron deficiency/IDA, as well as the exact mechanisms underlying the potential development of these nutritional complications in patients treated with incretin receptor agonists. Meanwhile, the prescription of incretin receptor agonists should not be unjustifiably restricted by the possible and modest risk of iron deficiency and IDA in patients with one or more approved indications for therapeutic use of these agents. Since no established guidelines currently exist for the prevention and management of iron deficiency and IDA in patients treated with incretin receptor agonists, we herein propose practical strategies to address these possible nutritional complications of incretin receptor agonist-based therapies. These proposed strategies should only be regarded as practical clinical approaches deriving from the existing recommendations for the prevention and management of iron deficiency and IDA, although their cost-effectiveness for the prevention and management of incretin receptor agonist-associated iron deficiency/IDA should be appropriately assessed in future clinical trials. Full article

The utilization of sugarcane molasses as a low-cost carbon source for riboflavin production is hindered by the reactive oxygen species (ROS) stress induced by its complex components, which suppresses microbial metabolism. To address this, we employed adaptive laboratory evolution (ALE) under progressively increasing stress to develop a sugarcane molasses-tolerant and high-yielding Ashbya gossypii. The adapted strain achieved a riboflavin titer of 298.39 ± 2.01 mg/L, representing a 99.4% increase over the parental strain (149.66 ± 4.97 mg/L), accompanied by a 96% increase in biomass (dry cell weight). Notably, the specific riboflavin production per unit biomass showed no significant difference between the two strains, indicating that the improved total yield was primarily driven by enhanced biomass accumulation. Transcriptomic analysis revealed the molecular basis for this enhanced biomass accumulation—the elevated expression of antioxidant enzymes (SOD1, PRDX5) mitigated ROS levels to support cellular growth, while the coordinated upregulation of the pentose phosphate pathway (E2.2.1.1) and purine metabolism genes (PPAT, ADE5, PFAS, ADSL) enhanced the supply of biosynthetic precursors, ribulose-5-phosphate (Ru5P) and GTP, for nucleotide biosynthesis and cell proliferation. These metabolic adjustments collectively enabled the adapted strain to achieve robust growth under sugarcane molasses stress, thereby driving the overall increase in riboflavin production. This study elucidates the molecular mechanism underlying ALE-improved riboflavin production and provides a promising strategy for its industrial fermentation using sugarcane molasses. Full article

Electrospinning (ES) can produce nonwoven fibrous mats with high surface area and interconnected porosity, making them attractive for biomedical and functional material applications. However, conventional ES often relies on volatile organic solvents, raising safety, environmental, and translational concerns. Fully aqueous (“green”) ES offers an appealing alternative, although many water-soluble polymers remain difficult to spin and may show limited stability under hydrated conditions. In this study, two fully aqueous binary systems, poly(vinylpyrrolidone)–sodium alginate (PVP–SA) and poly(vinylpyrrolidone)–riboflavin (PVP–RF), were investigated to decouple the roles of sodium alginate (SA) and riboflavin (RF) on solution behaviour, fibre formation, morphology, dry-state mechanical properties, and surface chemistry. Aqueous PVP solutions (20% w/v; molecular weight 1.3 MDa) were blended with SA (1–5 wt% relative to PVP) or RF (1–10 wt% relative to PVP). Electrical conductivity and rheological properties were evaluated prior to ES under controlled conditions, with simultaneous ultraviolet (UV) exposure at 344 nm during fibre collection. RF did not significantly alter conductivity (~0.74–0.75 µS·cm⁻¹), whereas SA increased conductivity up to 2.75 ± 0.03 µS·cm⁻¹ at 5 wt%. All formulations exhibited shear-thinning behaviour, while 10 wt% RF increased the zero-shear viscosity relative to neat PVP. Morphological analysis showed that low SA contents produced uniform fibres, whereas higher SA levels (4–5 wt%) led to bead defects and reduced fibre diameter (down to 85 ± 25 nm). Dry-state mechanical performance decreased with increasing SA content, while 10 wt% RF improved tensile strength and toughness, reaching an ultimate tensile strength of 5.21 ± 0.15 MPa and toughness of 40.51 ± 1.53 MJ·m⁻³. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) indicated subtle UV-driven redistribution of surface chemical states, consistent with mild photo-oxidative microstructural modification rather than extensive covalent network formation. Because the UV irradiance was not directly measured and wet-state stability was not assessed, the UV-related findings are interpreted as preliminary chemical evidence rather than confirmation of stabilized fibre mats. Overall, this work establishes a solvent-free aqueous ES platform in which ionic and photoactive additives can be used to tailor fibre morphology, dry-state mechanical behaviour, and surface characteristics without toxic reagents. Full article

Edible and medicinal mushrooms are widely studied for their bioactive compounds, yet their role as sources of essential vitamins remains inadequately defined and often overestimated. This review provides a critical assessment of vitamin composition in edible and medicinal mushrooms, with an emphasis on B-group vitamins and vitamin D₂, focusing on variability, bioavailability, and limitations for nutritional applications. Current evidence indicates that mushrooms can contribute to the intake of selected B vitamins, particularly riboflavin (B₂) and thiamine (B₁), at levels comparable to common plant foods. However, their relevance as a source of vitamin B₁₂ is highly uncertain due to pronounced compositional variability, the frequent occurrence of inactive corrinoid analogues, and limited evidence of physiological bioavailability. In contrast, vitamin D₂ represents a distinctive and technologically controllable feature of mushrooms, formed via the ultraviolet-induced conversion of ergosterol. Post-harvest UV exposure can substantially enhance vitamin D₂ content, enabling targeted biofortification strategies. Nevertheless, the nutritional significance of mushroom-derived vitamins is constrained by inconsistencies in reported concentrations, lack of standardized analytical methodologies, and insufficient clinical evidence. Overall, edible and medicinal mushrooms should not be regarded as universal natural sources of vitamins; rather, their nutritional relevance depends on species, cultivation conditions, post-harvest processing, analytical verification, and, particularly in the case of vitamin D₂, controlled UV-induced biofortification. Future research should prioritize standardized analytical approaches and well-designed human studies to support evidence-based nutritional applications. Full article

Background/Objectives: The gene solute carrier family 52 member 3 (SLC52A3) encodes riboflavin transporter-3, a transmembrane protein essential for riboflavin absorption. Emerging evidence suggests that metabolic transporters may play a role in tumor biology. This study aimed to investigate the expression patterns, prognostic significance, genetic alterations, and functional associations of SLC52A3 in gynecological cancers. Methods: A comprehensive bioinformatic analysis was conducted using multi-omics datasets from The Cancer Genome Atlas (TCGA). Gene expression and survival analyses were performed via GEPIA3. Genetic alterations, including mutations and copy number variations, were assessed using cBioPortal. Immune infiltration correlations were analyzed through TIMER3. Protein–protein interactions and gene enrichment analyses were performed using STRING and GEPIA2, followed by Gene Ontology (GO) and KEGG pathway analyses. Results: SLC52A3 expression was significantly upregulated in ovarian, cervical, and endometrial cancers. Reduced expression of SLC52A3 was associated with poorer overall survival and shorter progression-free interval specifically in endometrial cancer. Genetic alterations in SLC52A3 were not significantly associated with survival outcomes (OS, DFS, and PFS). Functional enrichment analysis indicated that SLC52A3 is involved in biological processes such as cell junction organization and protein localization to the plasma membrane. Additionally, SLC52A3 expression showed positive correlations with genes implicated in tumor progression and metastasis, including NECTIN4, PROM2, TACSTD2, PKP3, SEMA4B, and CD46. Conclusions: These findings suggest that SLC52A3 may serve as a potential prognostic biomarker in endometrial cancer and could play a role in tumor progression pathways. Its functional associations highlight its potential relevance as a therapeutic target, warranting further experimental validation. Full article

Cyanogenic glycosides in leafy vegetables pose significant food safety concerns because they release hydrogen cyanide (HCN) when plant tissue is disrupted. Although boiling is widely used for detoxification, its effects on nutritional quality and bioactive compounds remain insufficiently characterized. This study evaluated the effects of boiling on HCN, carotenoids, antioxidant capacity, and nutrient retention in Cnidoscolus aconitifolius (chaya) leaves. Antioxidant capacity was determined using the oxygen radical absorbance capacity, ferric reducing antioxidant power, and 2,2-diphenyl-1-picrylhydrazyl assays. An integrative nutrient retention index (NRI) was used to assess overall nutrient preservation. Boiling reduced HCN by 99.94%, confirming effective detoxification through hydrolysis, volatilization, and leaching. β-carotene showed high retention (95.8%), whereas thiamine (0.91%) and riboflavin (16.67%) were markedly reduced. Potassium retention was also low (24.85%). The total phenolic content and antioxidant capacity decreased significantly after boiling. The NRI indicated high retention of bioactive compounds (85.95%) but lower retention of vitamins (25.81%) and minerals (52.85%), yielding a global value of 54.92%. These findings highlight a trade-off between food safety and nutritional quality. Therefore, boiling remains a critical safety intervention for chaya and provides a useful model for optimizing processing conditions to balance detoxification with functional value. Full article

Background/Objectives: Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underlying its pathogenesis remain poorly understood. The present study was designed to explore these mechanisms from the perspective of targeted metabolomics. Methods: The HUA mice constructed by urate oxidase (Uox) gene knockout (KO) and their corresponding wild-type controls were employed for the present study. Serum clinical biochemical parameters were determined, and renal histopathological changes were evaluated using hematoxylin-eosin (HE) staining and Masson’s trichrome staining. A targeted metabolomic strategy based on multiple reaction monitoring (MRM) was utilized to profile the renal metabolic landscape of Uox-KO mice, and potential metabolic biomarkers for CUN were identified via multivariate data analysis. Results: Clinical biochemical analysis revealed a significant elevation in serum uric acid, creatinine, and urea nitrogen levels in Uox-KO mice compared with control mice. Histopathological observations confirmed a typical CUN phenotype in Uox-KO mice, characterized by renal tubular vacuolar degeneration and dilatation, desquamation of tubular epithelial cells into the lumen, neutrophil infiltration, glomerular crowding, and renal interstitial fibrosis. Metabolomic analysis identified a total of 291 differentially regulated metabolites in Uox-KO mice relative to control animals. These perturbed metabolites were involved in multiple key biochemical pathways, including amino acid biosynthesis, ABC transporter signaling pathway, purine metabolism, aminoacyl-tRNA biosynthesis, protein digestion and absorption, glycerophospholipid metabolism, and serotonergic synaptic transmission. Notably, pathological parameters, including biochemical measurements and histological observations, were significantly correlated with key differential metabolites associated with CUN progression. Furthermore, eleven differential metabolites (pyroglutamic acid, fructose, riboflavin, dimethyl-L-arginine, glucaric acid, indoxyl sulfate, palmitoylethanolamide, trimethylamine N-oxide, 3-hydroxyanthranilic acid, spermidine, and hippuric acid) were identified as potential metabolic biomarkers for the diagnosis and prognosis of CUN. Conclusions: These findings illustrate that targeted tissue metabolomic analysis constitutes a powerful tool for deciphering the molecular mechanisms of diseases, thus offering novel insights into the pathogenesis of CUN. Full article

The gut–lung axis is important in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis; however, most studies rely on low-resolution 16S rRNA sequencing, and integrated multi-omics investigations in Chinese COPD populations are scarce. A total of 104 participants including 74 stable COPD patients and 30 healthy controls from northern China were recruited, and shotgun metagenomic sequencing and untargeted metabolomics were performed. Results showed that alpha diversity of the gut microbiota did not differ significantly between COPD patients and healthy controls, whereas beta diversity showed clear separation. Marked differences in microbial composition from phylum to species levels (e.g., Oscillospiraceae) and altered microbial functions (signal transduction, antibiotic resistance, etc.) were observed in COPD patients. Metabolomic profiling identified 497 differential fecal metabolites and 1260 differential serum metabolites in COPD patients. Importantly, serum riboflavin levels were significantly reduced and positively correlated with pulmonary function indices as well as the key differential gut microbial functional gene K11752. Serum metabolite eremopetasinorol exhibited high diagnostic accuracy for COPD (AUC = 0.947, 95% CI: 0.8–0.98), surpassing fecal metabolites and microbial features. This study provides integrated metagenomic and metabolomic characterization of gut microbiota alterations in Chinese COPD patients, offering novel insights for biomarker discovery and targeted intervention strategies. Full article

Based on previous findings that fiber digestibility and rumen fermentation in weaned buffalo calves were improved by a roughage combination of dried sugarcane leaves (SDL) and peanut vine (PV), this study reveals that the mechanism for improving fiber digestibility and growth performance involves increasing Succiniclasticum abundance and 3-methoxytyramine-betaxanthin level, which consequently increases ruminal acetate and propionate. Twenty-one calves were fed pelleted diets with roughage combinations the 15% SDL combined with PV (S15PV, 15% SDL + 15% PV), the 22.5% SDL combined with PV (S22.5PV, 22.5% SDL + 7.5% PV), or the 30% SDL combined with PV (S30PV, 30% SDL) for 63 days. The results showed no significant differences in α-diversity and β-diversity among the three groups (p > 0.05). A significantly higher relative abundance of Succiniclasticum was observed in the S22.5PV group than in the other two groups, by 241.57% and 136.25%, respectively (p < 0.05), and its effects were primarily exerted through carbohydrate and amino acid metabolism pathways. Differential metabolites were mainly enriched in cofactor/vitamin metabolism (vitamin B6, riboflavin) and amino acid pathways (arginine, tryptophan). By PLS-DA analysis, significantly higher levels of Bentyl and 3-Methoxytyramine-betaxanthin were observed in the S22.5PV group compared to the S15PV and S30PV groups, respectively. Positive correlations were observed between Succiniclasticum and NDFD, ADFD, acetic acid, propionic acid, isovaleric acid, as well as 3-Methoxytyramine-betaxanthin (p < 0.05). In conclusion, the rumen microbial diversity was not altered by the roughage combinations of dried sugarcane leaves and peanut vine, but the abundance of Succiniclasticum and the level of 3-Methoxytyramine-betaxanthin were significantly correlated with NDFD and ADFD, which enriched ruminal AA and PA, and may thus be associated with improved growth performance. Full article

Bovine milk adulteration with coconut milk poses a significant threat to food safety, as both liquids are visually similar yet nutritionally distinct. This study presents an integrated analytical framework combining excitation–emission matrix (EEM) fluorescence spectroscopy with chemometric and deep learning techniques to detect and quantify coconut milk adulteration in bovine milk across nine concentration levels (0–100% v/v). Parallel factor analysis (PARAFAC) resolved two dominant fluorescent components, tryptophan (λ ex/em: 290/350 nm) and riboflavin (λ ex/em: 450/525 nm), whose scores decreased monotonically with increasing adulteration, confirming their role as key chemical biomarkers. For quantitative prediction, PLSR and 1D-CNN models were developed using emission spectra at three excitation wavelengths, with best performances achieved at 450 nm (PLSR: R²P = 0.97, RMSEP = 5.00%; 1D-CNN: R²P = 0.94, RMSEP = 6.75%). A lightweight 2D-CNN utilizing full EEM contour maps as image inputs outperformed all quantitative models, achieving R²P = 0.99, RMSEP = 2.36%, and RPD = 12.97, demonstrating the advantage of preserving the full two-dimensional fluorescence topology over discrete wavelength selection. These results confirm that EEM combined with 2D-CNN provides a highly accurate and non-destructive tool for dairy authentication. Full article

Cross-linking is a therapy that strengthens the cornea and helps slow the progression of keratoconus. This therapeutic surgery has evolved from a single standardized protocol to a diverse array of techniques tailored to improve safety, efficacy, patient comfort, and accessibility. It represents a transformative advancement in keratoconus treatment. Its ability to biomechanically reinforce the cornea and halt disease progression has revolutionized patient care, reducing the burden of advanced keratoconus and improving long-term visual outcomes. Ongoing refinements in technique continue to enhance its efficacy, safety, and patient comfort, securing its role as a cornerstone of modern ophthalmic practice. This process involves creating new covalent bonds between corneal fibers using a photosensitising substance called riboflavin. The effectiveness of cross-linking can be assessed by introducing the severity index, which provides a quantitative measure of the therapeutic outcome. This index allows for a more objective evaluation for both prognostic and therapeutic purposes. Full article

Limosilactobacillus fermentum SHY0006 was isolated from Miao sour soup, a traditional fermented food from Guizhou, China, and systematically evaluated for its safety, metabolic functionality, and stress adaptability using phenotypic assays combined with whole-genome sequencing. SHY0006 exhibited no hemolytic activity and harbored no detectable virulence-associated or acquired antibiotic resistance genes, supporting its safety profile. Functionally, SHY0006 improved lipid metabolism and insulin resistance in both cell and animal models. In hyperlipidemic mice, hepatic triglyceride accumulation was markedly reduced, accompanied by favorable modulation of serum lipid parameters, including LDL-C, HDL-C, and free fatty acids. In diabetic mice, the strain improved insulin tolerance test (ITT) performance, indicating enhanced systemic insulin sensitivity. Whole-genome analysis revealed complete biosynthetic pathways for riboflavin and folate, along with extensive carbohydrate utilization capacity, highlighting its metabolic versatility. In addition, SHY0006 exhibited strong tolerance to environmental stress, supporting its potential viability in food matrices and gastrointestinal conditions. Collectively, these findings suggest that SHY0006 is a safe and metabolically versatile probiotic candidate with potential applications in functional foods targeting metabolic health. Full article

To address the environmental sensitivity and low bioavailability of riboflavin, this study constructed a soybean protein isolate fibril (SPF)/κ-carrageenan (κC) composite gel delivery system. This study systematically investigated the effects of two independent variables (protein type: SPI/SPF; κC concentration: 2, 4, 6, 8 mg/mL) on the gel structural stability, riboflavin encapsulation performance, and in vitro digestive delivery characteristics of the system. Thioflavin T (ThT) fluorescence and ultraviolet (UV) absorption spectroscopy confirmed the successful preparation of SPF and verified specific intermolecular interactions between SPF and κC. Intermolecular forces, protein leaching rates, and differential scanning calorimetry (DSC) results indicated that compared with SPI-κC composite gels, κC regulates SPF molecular conformation via hydrogen bonding and hydrophobic interactions to exert a synergistic effect. This conformational regulation significantly reduced the protein leaching rates in SPF-κC composite gels, elevated the thermal denaturation temperatures (up to 79.82 °C), and enhanced the gel structural stability. As the κC concentration increased, the environmental stability of SPF-κC riboflavin-loaded composite gels were markedly enhanced, which effectively delayed the gel degradation during simulated gastrointestinal digestion. This was manifested as a reduced protein loss rate (reduced to 22.23%). At a κC concentration of 8 mg/mL, the in vitro release mechanism of riboflavin shifted from Fickian to non-Fickian diffusion. Full article

Aryl halides are important intermediates for chemical synthesis. However, the negative reduction potential up to −2.7 V (vs. SCE) makes photoredox conversion of aryl halides by reductive dehalogenation to aryl radicals for chemical transformations difficult. Inspired by the outstanding photophysical properties of deazaflavin and triphenylamine, as well as results of theoretical calculations, we attached the diphenylamino group to C8 of deazaflavin, and the resulting compounds look fabricated by “fusing” deazaflavin and triphenylamine (TPA) together by sharing the benzene ring. We also introduced alkyl and aryl moieties to C5 and afforded a series of deazaflavin derivatives (dFLs), namely 10-butyl-8-(diphenylamino)-3,5-dimethylpyrimido[4,5b]quinoline-2,4(3H,10H)-dione (TPAdFlMe), 10-butyl-8-(diphenylamino)-3-methyl-5-(trifluoromethyl)pyrimido[4,5-b]quinoline-2,4(3H,10H)-dione(TPAdFlTF) and 10-butyl-8-(diphenylamino)-3-methyl-5-phenylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TPAdFlPh), and investigated their photophysical properties and performance as sensitizers in the photodehalogenation of aryl halides. We showed that the photophysical properties are significantly improved in these dFLs. The absorption bands of dFLs are redshifted and the absorbance is more than double that of riboflavin tetraacetate (RFTA). The singlet oxygen quantum yields of TPAdFlMe, TPAdFlTF and TPAdFlPh are 0.42, 0.25 and 0.39, respectively, and the corresponding redox potentials are −1.75, −0.75 and −1.71 V vs. Ag/Ag⁺, respectively, comparable to known deazaflavin-based sensitizers. Originating from these properties, TPAdFlMe and TPAdFlPh are capable of sensitizing the full photodehalogenation of 0.038 mmol p-iodoanisole, and the yields of the photodehalogenation of 0.038 mmol p-bromoanisole are 67 and 69%, respectively. They also demonstrate exceptional performance in the photodehalogenation of halides of polycyclic aromatics with yields in the range of 73% for 1-benzhydryl-3-bromobenzene to 100% for 1-bromonapthalene in 18 h runs. The performance of TPAdFlMe and TPAdFlPh in photodehalogenation are already comparable to recently reported deazaflavin-based sensitizers, and we propose the transformation would proceed though the consecutive photo-induced electron transfer (conPET) mechanism with consecutive excitation of charged deazaflavin-based radicals under light irradiation as the key step to generating the aryl radicals, and the vital role of sensitizer-based radicals is further confirmed by mechanistic investigations. We expect the findings will help to design novel flavin-based triplet sensitizers for photoredox catalytic organic transformations. Full article