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ABSTRACT Milk, owing to its nutritional value, is a staple commodity in daily life. Ensuring its integrity and authenticity is paramount for researchers and the food industry. To evaluate spoilage and adulteration of milk, we proposed a robust and reliable optical method to guarantee milk quality by utilizing riboflavin as an internal biomarker. By precisely controlling the content of Eu3+, Tb3+, and Gd3+ ions, a two‐dimensional ratiometric luminescence lanthanide coordination polymer (Ln‐CP) with adjustable emission centers was synthesized for the detection of riboflavin (RF), leveraging a Förster resonance energy transfer (FRET) and photoinduced electron transfer (PET) process. This method demonstrates high sensitivity and selectivity towards RF and has been successfully applied to the detection of RF in both milk and calf serum. [ABSTRACT FROM AUTHOR]

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/ undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD. [ABSTRACT FROM AUTHOR]

Summary: A few Capsicum (pepper) species produce yellow‐colored floral nectar, but the chemical identity and biological function of the yellow pigment are unknown.A combination of analytical biochemistry techniques was used to identify the pigment that gives Capsicum baccatum and Capsicum pubescens nectars their yellow color. Microbial growth assays, visual modeling, and honey bee preference tests for artificial nectars containing riboflavin were used to assess potential biological roles for the nectar pigment.High concentrations of riboflavin (vitamin B2) give the nectars their intense yellow color. Nectars containing riboflavin generate reactive oxygen species when exposed to light and reduce microbial growth. Visual modeling also indicates that the yellow color is highly conspicuous to bees within the context of the flower. Lastly, field experiments demonstrate that honey bees prefer artificial nectars containing riboflavin.Some Capsicum nectars contain a yellow‐colored vitamin that appears to play roles in (1) limiting microbial growth, (2) the visual attraction of bees, and (3) as a reward to nectar‐feeding flower visitors (potential pollinators), which is especially interesting since riboflavin is an essential nutrient for brood rearing in insects. These results cumulatively suggest that the riboflavin found in some Capsicum nectars has several functions. [ABSTRACT FROM AUTHOR]

Background: Nutri Crackle rusk, developed using an innovative pigmented variety of black rice flour, possesses a rich nutritional profile with essential amino acids, dietary fibers, and antioxidants, offering unique health benefits beyond traditional rice varieties. Establishing healthy eating habits during childhood cancer treatment is crucial for long-term well-being. Mindful consumption, incorporating Nutri Crackle rusk instead of empty-calorie snacks, can significantly improve the quality of life of childhood cancer survivors during their survivorship period. Materials and Methods: The novel Nutri Crackle rusk using black rice flour was developed under proper hygienic conditions. Semi-trained panel and consumer panel members evaluated the organoleptic properties of the developed product. Nutrient components of the formulated Nutri Crackle rusk were examined through an organoleptic assessment. Results: The nutrient composition of the formulated Nutri Crackle rusk was analyzed using a standard procedure. Sensory evaluation indicated positive feedback, with an overall acceptability score of 8.01. Nutrient analysis revealed a well-rounded profile, emphasizing energy provision (464.285 kcal), (11.97 g protein), (11.29 g fiber), and essential micronutrients (zinc, iron, and vitamins B1 and B2). Nutri Crackle rusk is a favorable and potentially beneficial snack for this vulnerable group. Conclusion: The study signifies that the novel healthy Nutri Crackle rusk is rich in fiber, zinc, iron, protein, vitamin B1, and vitamin B2. Intake of the developed Nutri Crackle rusk could be a healthy alternative for pediatric cancer patients and cancer survivors. [ABSTRACT FROM AUTHOR]

Development of multi-, extensively-, and pandrug-resistant (MDR, XDR, and PDR) strains of Pseudomonas aeruginosa remains a major problem in medical care. The present study evaluated the effect of antimicrobial photodynamic therapy (aPDT) as a monotherapy and in combination with colistin against P. aeruginosa isolates. Two P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Minimum inhibitory concentration (MIC) of colistin was determined by the colistin broth disk elution (CBDE) and the reference broth microdilution (rBMD) methods. aPDT was performed using the photosensitizer (Ps) riboflavin at several concentrations and a light-emitting diode (LED) emitting blue light for different irradiation times with or without colistin at 1/2 × MIC concentration. Both PA1 and PA2 isolates were identified as colistin-resistant P. aeruginosa with a MIC ≥4 μg/mL by the CBDE and MICs of 512 μg/mL and 256 μg/mL, respectively, by the rBMD. In aPDT, neither riboflavin nor LED light alone had antibacterial effects. The values of colony forming units per milliliter (CFU/mL) in both isolates were significantly reduced by LED + Ps treatments in a time-dependent manner (LED irradiation time) and dose-dependent manner (Ps concentration). In comparison with control, treatment with Ps (50 μM) + LED (120 s) and Ps (100 μM) + LED (120 s) resulted in 0.27 log 10 CFU/mL and 0.43 log 10 CFU/mL reductions in PA1, and 0.28 log 10 CFU/mL and 0.34 log 10 CFU/mL reductions in PA2, respectively, (P < 0.01). The best results were obtained after the combination of aPDT followed by colistin, which increased bacterial reduction, resulting in a 0.41−0.7 log 10 CFU/mL reduction for PA1 and 0.35−0.83 log 10 CFU/mL reduction for PA2 (P = 0.001). This study suggests the potential implications of aPDT in combination with antibiotics, such as colistin for treatment of difficult-to-treat P. aeruginosa infections. [ABSTRACT FROM AUTHOR]

Methionine is an essential amino acid for mammals and it is limiting for monogastric animals. It can be oxidized easily by UV light. This could influence the bioaccessibility and bioavailability of methionine. In this work, the photosensitized degradation of peptide-bound methionine in the presence of riboflavin was investigated in a model system. Capillary electrophoresis was employed to analyze the time course of the degradation. The products were identified by liquid chromatography coupled to mass spectrometry (LC–MS/MS). Benzoyl methionine was degraded by 50% during UV irradiation in the presence of riboflavin after 5.0 min with 10 mol% riboflavin and 6.4 min with 3 mol% riboflavin. Homocysteine (16–20 mol%) and β-aspartic semialdehyde (ca. 30 mol%) were found as major degradation products next to methionine sulfoxide (ca. 25 mol%). A smaller molar ratio of riboflavin led to a higher formation of aspartic semialdehyde. The formation of homocysteine was paralleled by the formation of formaldehyde. Furthermore, the experiment was transferred to small peptides, which showed the analogous degradation products of peptide-bound methionine. [ABSTRACT FROM AUTHOR]

Brain oxygen deprivation causes morphological damage involved in the formation of serious pathological conditions such as stroke and cerebral palsy. Therapeutic methods for post-hypoxia/anoxia injuries are limited and still have deficiencies in terms of safety and efficacy. Recently, clinical studies of stroke have reported the use of drugs containing riboflavin for post-injury clinical rehabilitation, however, the effects of vitamin B2 on exposure to cerebral oxygen deprivation are not completely elucidated. This review aimed to investigate the potential antioxidant, anti-inflammatory and neuroprotective effects of riboflavin in cerebral hypoxia/anoxia. After a systematic search, 21 articles were selected, 8 preclinical and 12 clinical studies, and 1 translational study. Most preclinical studies used B2 alone in models of hypoxia in rodents, with doses of 1–20 mg/kg (in vivo) and 0.5–5 µM (in vitro). Together, these works suggested greater regulation of lipid peroxidation and apoptosis and an increase in neurotrophins, locomotion, and cognition after treatment. In contrast, several human studies have administered riboflavin (5 mg) in combination with other Krebs cycle metabolites, except one study, which used only B2 (20 mg). A reduction in lactic acidosis and recovery of sensorimotor functions was observed in children after treatment with B2, while adults and the elderly showed a reduction in infarct volume and cognitive rehabilitation. Based on findings from preclinical and clinical studies, we conclude that the use of riboflavin alone or in combination acts beneficially in correcting the underlying brain damage caused by hypoxia/anoxia and its inflammatory, oxidative, and behavioral impairments. [ABSTRACT FROM AUTHOR]

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Alcoholic liver disease (ALD) is a disease with high incidence, limited therapies, and poor prognosis. The present study aims to investigate the effect of riboflavin on ALD and explore its potential therapeutic mechanisms. C57BL/6 mice were divided into the control, alcohol, and alcohol+ riboflavin groups. 16S rRNA-seq and RNA-seq analysis were utilized to analyze the polymorphism of intestinal microbiota and the transcriptome heterogeneity respectively. KEGG and GO enrichment analysis were performed. CIBERSORTx was applied to evaluate the immune cell infiltration level. Publicly available transcriptome data of ALD was enrolled and combined with the RNA-seq data to identify the immune subtypes of ALD. Pathological and histology analysis demonstrated that riboflavin reversed the progression of ALD. 16S rRNA-seq results showed that riboflavin could regulate alcohol-induced intestinal microbiota alteration. Intestinal microbiota polymorphism analysis indicated that VLIDP may contribute to the progression of ALD. Based on the VLIDP pathway, two subtypes were identified. Immune microenvironment analysis indicated that the upregulated inflammatory factors may be important regulators of ALD. In conclusion, intestinal microbiota homeostasis was associated with the protective effect of riboflavin against ALD, which was likely mediated by modulating inflammatory cell infiltration. Riboflavin emerges as a promising therapeutic candidate for the management of ALD. Riboflavin attenuates alcoholic liver disease progression, regulates alcohol-induced changes in intestinal microbiota, and affects inflammatory cell infiltration suggesting that riboflavin may be a potentially effective agent for treating ALD [ABSTRACT FROM AUTHOR]

Simple Summary: Pigeons are one of the oldest domesticated birds in the world, and humans have been raising pigeons for thousands of years. Pigeon meat is edible and rich in protein, polyunsaturated fatty acids, minerals, and vitamins. As a late-maturing bird, pigeons need to be fed by their parents to obtain nutrients. Therefore, the dietary nutritional level of pigeon breeders is vital for production and reproduction. However, there is currently no explicit nutritional requirement for pigeon riboflavin internationally. This study aimed to investigate the effects of dietary riboflavin levels on the reproductive performance of pigeon breeders and the growth performance and carcass traits of offspring squabs to estimate the riboflavin requirement of pigeon breeders. The natural riboflavin content in the basic diet of corn–peas–soybean–wheat–sorghum–corn gluten is 1.20 mg/kg. Different doses of riboflavin (0, 2.5, 5, 10, and 15 mg/kg) were supplemented with the basal diet to produce five dietary treatments with total riboflavin levels of 1.20, 3.70, 6.20, 10.20, and 16.20 mg/kg. A total of 120 pairs of White King pigeons, aged 60 wks, were randomly allocated into five treatment groups, each consisting of 24 pairs. Each pair was individually raised for 8 wks. After the experiment, an assessment was conducted to evaluate the reproductive performance of the pigeon breeders, as well as the growth and carcass traits of offspring squabs at 28 days of age. The results showed that the dietary riboflavin levels had no significant effect on body weight, feed intake, egg weight, egg production, and egg fertility (p > 0.05). However, pigeons fed a diet without riboflavin had the lowest egg hatchability, egg yolk color, carcass trait, and riboflavin status, while exhibiting higher liver weight and liver index (p < 0.05). Moreover, the indices above showed increased or decreased linearly as the level of riboflavin was increased in the diet. Based on the broken-line regression model, pigeon breeders were determined to require a dietary riboflavin content of 11.4, 13.6, 13.4, 6.60, 4.28, 4.47, 4.67, 6.69, and 6.82 mg/kg to optimize hatchability, eviscerated weight, half-eviscerated weight, breast muscle weight, breast muscle percentage, liver weight, liver index, egg yolk riboflavin, and squab plasma riboflavin, respectively. In conclusion, the optimal supplemental dosage of riboflavin in the diets of pigeon breeders is 13.6 mg/kg. [ABSTRACT FROM AUTHOR]

Collagen crosslinking employing ultraviolet A rays and riboflavin (UVA/R) has emerged as a pivotal technique in clinical therapies, especially in ophthalmology since the 1990s. Despite its clinical adoption, the lack of clarity of the detailed mechanism and the imperative for a refined manufacturing process necessitates further investigation. This study advances the understanding of UVA/R crosslinked collagen, concentrating on identifying the primary crosslinking sites using seven synthetic peptides and exploring the pathways of riboflavin‐mediated crosslinking. The results demonstrate that tyrosine residues are key crosslinking sites, and riboflavin plays a dual role as both a catalyst and a competitive inhibitor in the crosslinking process. Furthermore, the UVA/R crosslinked collagen matrix exhibits a more harmonious balance between stability and degradability compared with chemically crosslinked collagen matrices, coupled with superior mechanical properties and augmented biocompatibility. In vivo experiments further validate its excellent biocompatibility, reduced tissue inflammation, and promotion of tissue regeneration. The research provides crucial insights into collagen crosslinking mechanisms, paving the way for the development of sophisticated collagen‐based biomaterials tailored for biomedical applications. [ABSTRACT FROM AUTHOR]

Insects and their gut bacteria form a tight and beneficial relationship, especially in utilization of host nutrients. The red turpentine beetle (RTB), a destructive and invasive pine pest, employs mutualistic microbes to facilitate its invasion success. However, the molecular mechanism underlying the utilization of nutrients remains unknown. In this study, we found that gut bacteria are crucial for the utilization of D-glucose, a main carbon source for RTB development. Downstream assays revealed that gut bacteria-induced gut hypoxia and the secretion of riboflavin are responsible for RTB development by regulating D-glucose transport via the activation of a hypoxia-induced transcription factor 1 (Hif-1α). Further functional investigations confirmed that Hif-1α mediates glucose transport by direct upregulation of two glucose transporters (ST10 and ST27), thereby promoting RTB development. Our findings reveal how gut bacteria regulate the development of RTB, and promote our understanding of the mutualistic relationship of animals and their gut bacteria. [ABSTRACT FROM AUTHOR]

Garlic (Allium sativum L.) is one of the most esteemed plants due to its medicinal properties. Its health benefits for humans are attributed to its chemical compounds. Few studies characterize garlic genotypes cultivated in Romania concerning their chemical composition. In this context, this study aimed to determine the chemical compounds for 16 local garlic genotypes cultivated under the same climatic and technological conditions. The chemical characteristics studied were the total phenolic content (TPC), total flavonoid content (TFC), reducing sugar content, antioxidant activity (AO), vitamin C, and acidity level. Chemical composition varied significantly among genotypes: TPC ranged from 656.07 to 1317.32 µg GAE/g FW; TFC ranged from 427.08 to 1447.90 µg QE/g FW; vitamin C ranged from 3.24 to 5.37 mg/g FW; reducing sugar content ranged from 3.24 to 5.37 mg/g FW; and the acidity level for the control was 6 meq/100 g. Among the selected genotypes, differences were observed between 3.48 and 11.02 meq/100 g. Significant correlations were noted between different compounds, specifically between TPC and AO, as well as between TPC and acidity level. In conclusion, this study highlights significant variability in terms of chemical composition of local garlic genotypes, which indicates notable differences between them and suggests that the genotypes may have different potential in medicinal and nutritional uses due to their distinctive chemical compositions. [ABSTRACT FROM AUTHOR]

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that respond to riboflavin biosynthesis and cytokines through TCR-dependent and -independent pathways, respectively. MAIT cell activation plays an immunoprotective role against several pathogens, however the functional capacity of MAIT cells following direct infection or exposure to infectious agents remains poorly defined. We investigated the impact of Varicella Zoster Virus (VZV) on blood-derived MAIT cells and report virus-mediated impairment of activation, cytokine production, and altered transcription factor expression by VZV infected (antigen+) and VZV exposed (antigen-) MAIT cells in response to TCR-dependent and -independent stimulation. Furthermore, we reveal that suppression of VZV exposed (antigen-) MAIT cells is not mediated by a soluble factor from neighbouring VZV infected (antigen+) MAIT cells. Finally, we demonstrate that VZV impairs the cytolytic potential of MAIT cells in response to riboflavin synthesising bacteria. In summary, we report a virus-mediated immune-evasion strategy that disarms MAIT cell responses. Author summary: Mucosal-associated invariant T (MAIT) cells are a uniquely specialised and substantial innate-T cell population that can rapidly respond to diverse bacterial and fungal pathogens through T cell receptor dependent recognition of riboflavin synthesis derived metabolite antigens. Additionally, MAIT cells can be triggered by local pro-inflammatory cues such as cytokines; therefore extending their functionality to non-riboflavin pathogens such as viral infections. Despite the capacity of MAIT cells to play a protective role against several classes of pathogens, there remains a dearth of studies investigating direct pathogenic suppression of MAIT cell functionality. Here, we investigate a previously uncharacterised interplay between MAIT cells and the causative agent of varicella (chickenpox) and shingles (zoster): Varicella Zoster Virus (VZV). VZV successfully infects and establishes lifelong latency within the host; in part to their ability to effectively manipulate several innate and adaptive axes of the host immune response. In this study, we report that VZV profoundly impairs MAIT cell activation in response to both riboflavin synthesis and cytokine stimulation, therefore resulting in a downstream paralysis of several effector functions such as cytokine production and cytotoxic potential. This work highlights a previously uncharacterised strategy of viral pathogens to effectively target and restrict the MAIT cell effector response. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionTo comparatively evaluate the influence of different riboflavin formulations and soaking durations on the anterior segment optical coherence tomography (AS-OCT) findings following accelerated corneal crosslinking (ACXL) at 9 mW/cm2 for in progressive keratoconus.In this prospective study, consecutive patients with progressive keratoconus were randomized into 4 groups. Group 1: hydroxypropyl methylcellulose (HPMC)-based riboflavin for 10 min; Group 2: HPMC-based riboflavin for 20 min; Group 3: dextran-based riboflavin (0.1%) for 30 min. Riboflavin soaking was followed by ultraviolet-A irradiation at 9 mW/cm2 for 10 min in all three groups. Group 4 underwent conventional CXL (CCXL) using Dresden protocol. The AS-OCT features of the crosslinked cornea were evaluated at postoperative month 1 and correlated to the clinical outcomes at postoperative month 12.The study enrolled 26 eyes of 26 patients in each group. In groups 1 and 2, the AS-OCT findings were similar (p > .05) and the demarcation lines depth (DLD) were deep as obtained following CCXL. The DLD was significantly shallower in group 3 compared to the other groups (p < .01). There were no between-group differences in regards to the visual, refractive, keratometric, and tomographic outcomes at postoperative month 12. No significant endothelial cell loss or any other clinically significant adverse event was encountered in any patient’s eye at 12 months follow-up.Although structural variations were noted in the crosslinked cornea, DLDs observed following ACXL (9 mW/cm2) using HPMC-based solution for 10 or 20 min were similar to those observed following CCXL. Whereas, ACXL (9 mW/cm2) using dextran-based solution for 30 min resulted in the shallowest DLD. Despite these remodeling differences, the visual, refractive and tomographic outcomes of all groups were comparable at postoperative 1-year follow-up. Studies with a greater number of patients and longer follow-ups are required to establish any relation between AS-OCT characteristics of crosslinked cornea and ACXL efficacy. [ABSTRACT FROM AUTHOR]

Purpose: With dairy products and fish being major sources of iodine in Switzerland, the growing popularity of plant-based alternatives may impact iodine nutrition. This study aimed to assess the iodine content in plant-based dairy and fish alternatives available in the Swiss market and compare them with conventional products. Methods: In 2022, a market survey was conducted in Zurich, Switzerland, to identify the plant-based dairy and fish alternatives available and assess their iodine content. To evaluate the impact of plant-based alternatives on iodine consumption in Switzerland, we modeled dietary scenarios by substituting the intake of dairy and fish items with plant-based alternatives. In addition, we investigated fortification with calcium, vitamins B2, B12, and D. Results: Out of 477 identified products, only four milk-alternative products were iodine fortified (median iodine concentration: 22.5 μg/100 ml). The median iodine concentration in unfortified plant-based alternatives was negligible compared to conventional dairy and fish products (milk: 0.21 vs 9.5 μg/100 ml; yogurt 0.36 vs 6.1 μg/100 g; cheese: 0.10 vs 20 μg/100 g; fish 0.50 vs 44 μg/100 g). Three portions of dairy per day as recommended by the Swiss Food Pyramid provide 25% of the RDA for iodine (150 μg/day), whereas substituting those with unfortified alternatives provides only 0.7% of the RDA. Conclusion: Only four out of 477 plant-based alternative products are iodine fortified in the Swiss market. Thus, the risk for consumers to miss out on the ca. 25% of the RDA for iodine by consuming plant-based alternatives is high, placing them at a risk for inadequate iodine intake. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The present study was conducted to assess the individual or combined effects of feeding dietary fat (whole-cracked rapeseed), nitrate, and 3-nitrooxypropanol (3-NOP) on protein profile, mineral composition, B vitamins, and nitrate residues in milk from dairy cows. A total of 48 Danish Holstein cows used in an 8 × 8 incomplete Latin square design were fed 8 factorially arranged diets: (30 or 63 g crude fat/kg DM) × (0 or 10 g nitrate/kg DM) × (0 or 80 mg 3-NOP/kg DM) over 6 periods of 21 d each. In each period, milk samples were collected from individual cows during the third week by pooling milk obtained from 4 consecutive milkings and analyzed for protein profile, including protein modifications, mineral composition, riboflavin, cobalamin, and presence of nitrate residues. Fat supplementation led to an increase in the phosphorylation degree of α S1 -CN by 8.5% due to a decreased relative proportion of α S1 -CN 8P and an increased relative proportion of α S1 -CN 9P and further to a decrease in the relative proportion of α S2 -CN by 2.4%. Additionally, fat supplementation decreased the relative proportions of glycosylated and unglycosylated forms of κ-CN, consequently leading to a 3.6% decrease in total κ-CN. In skim milk, K, Ca, P, and Mg concentrations were altered by individual use of fat, nitrate, and 3-NOP. Feeding nitrate resulted in a 5.4% increase in riboflavin concentration in milk, whereas supplementing 3-NOP increased the cobalamin concentration in milk by 21.1%. The nitrate concentration in milk was increased upon feeding nitrate, but this increased concentration was well below the maximum permissible limit of nitrate in milk (<50 mg/L). Overall, no major changes were observed in milk protein, and mineral compositions by feeding fat, nitrate, and 3-NOP to dairy cows, but the increased riboflavin and cobalamin concentrations by nitrate and 3-NOP, respectively, could be of beneficial nutritional value for milk consumers. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility of theranostics to determine the riboflavin concentration in the cornea using clinically available ophthalmic formulations during epithelium-off (epi-off) and transepithelial (epi-on) corneal cross-linking procedures. Methods: Thirty-two eye bank human donor corneas were equally randomized in eight groups; groups 1 to 3 and groups 4 to 8 underwent epi-off and epi-on delivery of riboflavin respectively. Riboflavin ophthalmic solutions were applied onto the cornea according to the manufacturers' instructions. The amount of riboflavin into the cornea was estimated, at preset time intervals during imbibition time, using theranostic UV-A device (C4V CHROMO4VIS, Regensight srl, Italy) and expressed as riboflavin score (d.u.). Measurements of corneal riboflavin concentration (expressed as µg/cm3) were also performed by spectroscopy absorbance technique (AvaLight-DH-S-BAL, Avantes) for external validation of theranostic measurements. Results: At the end of imbibition time in epi-off delivery protocols, the average riboflavin score ranged from 0.77 ± 0.38 (the average corneal riboflavin concentration was 213 ± 190 µg/cm3) to 1.79 ± 0.07 (554 ± 103 µg/cm3). In epi-on delivery protocols, the average riboflavin score ranged from 0.17 ± 0.01 to 0.67 ± 0.19 (corneal riboflavin concentration ranged from 6 ± 5 µg/cm3 to 122 ± 39 µg/cm3) at the end of imbibition time. A statistically significant linear correlation (P ≤ 0.05) was found between the theranostic and spectrophotometry measurements in all groups. Conclusions: Real-time theranostic imaging provided an accurate strategy for assessing permeation of riboflavin into the human cornea during the imbibition phase of corneal cross-linking, regardless of delivery protocol. A large variability in corneal riboflavin concentration exists between clinically available ophthalmic formulations both in epi-off and epi-on delivery protocols. [ABSTRACT FROM AUTHOR]

Introduction: Vaccination is the effective strategy for coronavirus disease 2019 (COVID‐19). However, few studies have investigated the association between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) immunoglobulin (Ig)G and vitamin D. Methods: This study aimed to investigate the association between SARS‐CoV‐2 IgG and active vitamin D analogs in hemodialysis patients. Blood samples were collected four times: before vaccination and 30, 60, and 90 days after vaccination, BNT162b2 (Pfizer©). Results: A total of 418 patients were enrolled. The mean age was 71.1 ± 12 years. Almost two thirds of the patients were prescribed active vitamin D analogs. The distribution of SARS‐CoV‐2 IgG before vaccination was 235 (93–454) AU/mL. After multiple regression analyses, active vitamin D analog use was found to be associated with higher SARS‐CoV‐2 IgG levels from prevaccination to 90 days postvaccination. Conclusion: This study demonstrated an association between higher SARS‐CoV‐2 IgG and active vitamin D analog use in hemodialysis patients. Clinical trial registration: The study information was registered in the UMIN‐CTR (UMIN 000046906). [ABSTRACT FROM AUTHOR]

The monitoring of antioxidants is crucial to prevent damage caused by reactive oxygen species (ROS). In this study, we introduce an innovative electrochemical sensor tailored for detecting riboflavin (RF), a powerful antioxidant. The sensor was developed by modifying a gold electrode (AuE) with cobalt oxide (Co3O4) and reduced graphene oxide (rGO). The resulting nanocomposite‐modified electrode (AuE/Co3O4‐rGO) exhibited a substantial surface area of 0.41 cm2 in the redox probe, leading to an enhanced RF peak characterized by remarkably low charge transfer resistance (1.61 KΩ) and a high exchange current density (18.6 μA/cm2). Under optimized conditions, the sensor achieved a limit of detection (LOD) for RF at 1.30 μM, over a concentration range of 6.5–42.2 μM. These results highlight the sensor's potential applicability in real‐world scenarios, including the analysis of milk and pharmaceutical samples. A kinetics study revealed that the electrochemical reaction involving RF is adsorption‐controlled, emphasising the critical role of surface interactions. The modified electrode's interaction with RF significantly influences overall reaction kinetics. These findings were further supported by density functional theory (DFT) calculations and molecular simulations. Our nanocomposite‐modified electrode provides valuable insights into the atomistic interactions governing sensor performance, advancing the field of electrochemical sensing for antioxidants like riboflavin. [ABSTRACT FROM AUTHOR]

Bacterial synthesis of vitamin B2 generates a by‐product, 5‐(2‐oxopropylideneamino)‐d‐ribityl‐aminouracil (5‐OP‐RU), with potent immunological properties in mammals, but it is rapidly degraded in water. This natural product covalently bonds to the key immunological protein MR1 in the endoplasmic reticulum of antigen presenting cells (APCs), enabling MR1 refolding and trafficking to the cell surface, where it interacts with T cell receptors (TCRs) on mucosal associated invariant T lymphocytes (MAIT cells), activating their immunological and antimicrobial properties. Here, we strategically modify this natural product to understand the molecular basis of its recognition by MR1. This culminated in the discovery of new water‐stable compounds with extremely powerful and distinctive immunological functions. We report their capacity to bind MR1 inside APCs, triggering its expression on the cell surface (EC50 17 nM), and their potent activation (EC50 56 pM) or inhibition (IC50 80 nM) of interacting MAIT cells. We further derivatize compounds with diazirine‐alkyne, biotin, or fluorophore (Cy5 or AF647) labels for detecting, monitoring, and studying cellular MR1. Computer modeling casts new light on the molecular mechanism of activation, revealing that potent activators are first captured in a tyrosine‐ and serine‐lined cleft in MR1 via specific pi‐interactions and H‐bonds, before more tightly attaching via a covalent bond to Lys43 in MR1. This chemical study advances our molecular understanding of how bacterial metabolites are captured by MR1, influence cell surface expression of MR1, interact with T cells to induce immunity, and offers novel clues for developing new vaccine adjuvants, immunotherapeutics, and anticancer drugs. [ABSTRACT FROM AUTHOR]

Background: Streptococcus mutans has been implicated as a primary causative agent of dental caries and one of its important virulence properties is an ability to form biofilm on tooth surfaces. Thus, strategies to prevent and control S. mutans biofilms are requested. The present study aimed to examine the eradication of S. mutans planktonic and biofilm cells using riboflavin (Rib)-mediated antimicrobial photodynamic therapy (aPDT) enhanced by postbiotic mediators derived from Lactobacillus species. Materials and methods: Minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of Rib and postbiotic mediators were determined. The antimicrobial and anti-biofilm effects of Rib-mediated aPDT (Rib plus blue light), Rib-mediated aPDT in combination with postbiotic mediators derived from Lactobacillus casei (LC) (aPDT+ LC), and Rib-mediated aPDT in combination with postbiotic mediators derived from Lactobacillus plantarum (LP) (aPDT+ LP) were evaluated. The anti-virulence potential of Rib-mediated aPDT, aPDT+ LC, and aPDT+ LP were assessed by measuring the expression of the gtfB gene using quantitative real-time polymerase chain reaction (qRT-PCR) at the highest concentrations of Rib, LC, and LP, at which the S. mutans had proliferation as the same as in the control (non-treated) group. Results: According to the results, the MIC doses of LC, LP, and Rib were 64 µg/mL, 128 µg/mL, and 128 µg/mL, respectively, while the MBC values of LC, LP, and Rib were 128 µg/mL, 256 µg/mL, and 256 µg/mL, respectively. Rib-mediated aPDT, aPDT+ LP, and aPDT+ LC showed a significant reduction in Log10 CFU/mL of S. mutans compared to the control group (4.2, 4.9, and 5.2 Log10 CFU/mL, respectively; all P < 0.05). The most destruction of S. mutans biofilms was observed after treatment with aPDT+ LC followed by aPDT+ LP and Rib-mediated aPDT (77.5%, 73.3%, and 67.6%, respectively; all P < 0.05). The concentrations of 31.2 µg/mL, 62.5 µg/mL, and 62.5 µg/mL were considered as the highest concentrations of LC, LP, and Rib, respectively, at which S. mutans replicates as same as the control group and were used for gtfB gene expression assay using qRT-PCR during Rib-mediated aPDT, aPDT+ LP, and aPDT+ LC treatments. Gene expression results revealed that aPDT+ LP and aPDT+ LC could decrease the gene expression level of gtfB by 6.3- and 5.7-fold, respectively (P < 0.05), while only 5.1-fold reduction was observed after Rib-mediated aPDT (P < 0.05). Conclusion: Our findings indicate that aPDT+ LP and aPDT+ LC hold promise for use as a treatment to combat S. mutans planktonic and biofilms growth as well as anti-virulence as a preventive strategy to inhibit biofilms development via reduction of gtfB gene expression. [ABSTRACT FROM AUTHOR]

Introduction: This study investigates the role of hypoxia-related genes in the neuroprotective efficacy of Yang Xue oral liquid (YXKFY) in Alzheimer's disease (AD) and Parkinson's disease (PD). Methods and results: Using differential expression and weighted gene coexpression network analysis (WGCNA), we identified 106 and 9 hypoxiaassociated genes in AD and PD, respectively, that are implicated in the transcriptomic and proteomic profiles. An artificial intelligence-driven hypoxia signature (AIDHS), comprising 17 and 3 genes for AD and PD, was developed and validated across nine independent cohorts (n = 1713), integrating 10 machine learning algorithms and 113 algorithmic combinations. Significant associations were observed between AIDHS markers and immune cells in AD and PD, including naive CD4+ T cells, macrophages, and neutrophils. Interactions with miRNAs (hsa-miR-1, hsa-miR-124) and transcription factors (USF1) were also identified. Single-cell RNA sequencing (scRNA-seq) data highlighted distinct expression patterns of AIDHS genes in various cell types, such as high expression of TGM2 in endothelial cells, PDGFRB in endothelial and mesenchymal cells, and SYK in microglia. YXKFY treatment was shown to repair cellular damage and decrease reactive oxygen species (ROS) levels. Notably, genes with previously dysfunctional expression, including FKBPL, TGM2, PPIL1, BLVRB, and PDGFRB, exhibited significant recovery after YXKFY treatment, associated with riboflavin and lysicamine. Conclusion: The above genes are suggested to be central to hypoxia and neuroinflammation responses in AD and PD, and are potential key mediators of YXKFY's neuroprotective action. [ABSTRACT FROM AUTHOR]

Since the early twentieth century, research on vitamins has revealed their therapeutic potential beyond their role as essential micronutrients. Riboflavin, known as vitamin B2, stands out for its unique characteristics. Despite numerous studies, riboflavin remains vital, with implications for human health. Abundantly present in various foods, riboflavin acts as a coenzyme in numerous enzymatic reactions crucial for human metabolism. Its role in energy production, erythrocyte synthesis, and vitamin metabolism underscores its importance in maintaining homeostasis. The impact of riboflavin extends to neurological function, skin health, and cardiovascular well-being, with adequate levels linked to reduced risks of various ailments. However, inadequate intake or physiological stress can lead to deficiency, a condition that poses serious health risks, including severe complications. This underscores the importance of maintaining sufficient levels of riboflavin for general wellness. The essential role of riboflavin in immune function further emphasises its significance for human health and vitality. This paper examines the diverse effects of riboflavin on health and stresses the importance of maintaining sufficient levels for overall well-being. [ABSTRACT FROM AUTHOR]

Treating bacteremia caused by antibiotic-resistant bacteria is a global concern. Antibacterial photodynamic inactivation is a promising strategy to combat it. However, it's challenging to achieve the inactivation of antibiotic-resistant bacteria in whole blood because of its opacity and complexity. We investigated a riboflavin photodynamic method to effectively inactivate antibiotic-resistant bacteria in whole blood. Four strains of antibiotic-resistant bacteria were isolated, identified, and cultured in this research: methicillin-resistant Staphylococcus aureus (MRSA), pan-drug-resistant Acinetobacter baumannii (PDRAB), ESBLs-producing Escherichia coli (EPEC) and pan-drug-resistant Klebsiella pneumoniae (PDRKP). To simulate bacteremia, antibiotic-resistant bacteria was added into whole blood. Whole blood was treated using riboflavin photodynamic method with ultraviolet irradiation (308 nm and 365 nm). The ultraviolet irradiation dose was divided into 18 J/cm², 36 J/cm², and 54 J/cm². Microbial count of antibiotic-resistant bacteria in whole blood was used for evaluating inactivation effectiveness. The roles of red blood cells, lymphocytes, coagulation factors, and platelets in whole blood were assessed. In results, inactivation effectiveness increased as the ultraviolet dose increased from 18 J/cm² to 54 J/cm². At the dose of 18 J/cm², inactivation effectiveness of four antibiotic-resistant bacteria were more than 80%, while only 67% of MRSA. The antibacterial effect was enhanced by the combination of riboflavin photodynamic treatment and antibiotic. The red blood cell function was susceptible to ultraviolet dose. At the dose of 18 J/cm², hemolysis rate was less than 0.8% and there was no change in levels of ATP and 2,3-DPG. At the same dose, the proliferation, cell killing, and cytokine secretion activities of lymphocytes decreased 20--70%; Factor V and Factor VIII activities decreased 50%; Fibrinogen and platelet function loss significantly but reparable. Consequently, we speculated that riboflavin photodynamic method with a ultraviolet dose of 18 J/cm² was effective in inactivating four antibiotic- resistant bacteria in whole blood while whole blood function was preserved. We also provided a novel extracorporeal circulation phototherapy mode for treating bacteremia caused by antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionsResearch exploring the link between dietary riboflavin intake and cognitive decline in this demographic is limited. Our aim was to examine the association between riboflavin intake levels and cognitive decline.The National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 were utilized in this cross-sectional analysis. The Consortium to Establish a Registry for Alzheimer's Disease test Word Learning delayed recall trial (DR), Digit Symbol Substitution Test (DSST), Animal Fluency Test(AFT) and Z test were used to evaluate cognitive performance. Multivariate logistic regression, restricted cubic spline and subgroup analysis were performed to evaluate the associations between riboflavin intake and cognitive decline.The study included a total of 2255 patients, with 47.9% being male. The incidence of cognitive decline was 23.8%. After adjusting for all selected covariates, we found that high riboflavin intake was associated with a lower risk of cognitive impairment in adults in the United States. When riboflavin intake was used as a Categorical variable, compared to those with the lowest intake, the odds ratio (OR) of individuals with the highest riboflavin intake for DR test, AFT test, DSST test and Z test were 0.73 (95% CI: 0.53~1), 0.68(95% CI: 0.49–0.96),0.53(95% CI: 0.37–0.77) and 0.56(95% CI: 0.39–0.8). The study also found an L-shaped association between riboflavin intake and cognitive decline, with an inflection point at approximately 2.984 mg/d.Our cross-sectional study in a nationwide sample of American old adults suggests that dietary riboflavin intake was negative associated with cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived exosomes (SC-exos) played a direct induction role while fibroblast-derived exosomes (Fb-exos) had no obvious induction role. The induction role of neural stem cell (NSC)-derived exosomes (NSC-exos) has also been widely confirmed. However, no studies have compared the induction effects of these three types of cells at the same time. Therefore, by investigating the effect of these three cell-derived exosomes upon the induction of BMSCs to differentiate into SCs, this study explored the role of different exosomes in promoting the differentiation of stem cells into SCs cells, and conducted a comparison between the two groups by RNA sequencing to further narrow the range of target genes and related gene pathways in order to study their related mechanisms. Materials and methods: We extracted exosomes from SCs, fibroblasts (Fb) and neural stem cells (NSC) and then investigated the ability of these exosomes to induce differentiation into BMSCs under different culture conditions. The expression levels of key proteins and gene markers were detected in induced cells by fluorescence immunoassays, western blotting and polymerase chain reaction (PCR); then, we statistically compared the relative induction effects under different conditions. Finally, we analyzed the three types of exosomes by RNA-seq to predict target genes and related gene pathways. Results: BMSCs were cultured by three media: conventional (no induction), pre-induction or pre-induction + original induction medium (ODM) with exosomes of the same cell origin under different culture conditions. When adding the three different types of exosomes separately, the overall induction of BMSCs to differentiate into SCs was significantly increased (P < 0.05). The induction ability was ranked as follows: pre-induction + ODM + exosome group > pre-induction + exosome group > non-induction + exosome group. Using exosomes from different cell sources under the same culture conditions, we observed the following trends under the three culture conditions: RSC96-exos group ≥ NSC-exos group > Fb-exos group. The overall ability to induce BMSCs into SCs was significantly greater in the RSC96-exos group and the NSC-exos group. Although there was no significant difference in induction efficiency when comparing these two groups, the overall induction ability of the RSC96-exos group was slightly higher than that of the NSC-exos group. By combining the differentiation induction results with the RNA-seq data, the three types of exosomes were divided into three comparative groups: RSC vs. NSC, RSC vs. Fb and NSC vs. Fb. We identified 203 differentially expressed mRNA target genes in these three groups. Two differentially expressed genes were upregulated simultaneously, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). We did not identify any co-upregulated target genes for the miRNAs, but did identify one target gene of the lncRNAs, namely ENSRNOG00000065005. Analysis identified 90 GO terms related to nerves and axons in the mRNAs; in addition, KEGG enrichment and GASA analysis identified 13 common differential expression pathways in the three groups. Conclusions: Our analysis found that pre-induction + ODM + RSC96/NSC-exos culture conditions were most conducive with regards to induction and differentiation. RSC96-exos and NSC-exos exhibited significantly greater differentiation efficiency of BMSCs into SCs. Although there was no statistical difference, the data indicated a trend for RSC96-exos to be advantageous We identified 203 differentially expressed mRNAs between the three groups and two differentially expressed target mRNAs were upregulated, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). 90 GO terms were related to nerves and axons. Finally, we identified 13 common differentially expressed pathways across our three types of exosomes. It is hoped that the efficiency of BMSCs induction differentiation into SCs can be improved, bringing hope to patients and more options for clinical treatment. [ABSTRACT FROM AUTHOR]

Background: The energy/protein imbalance in a low-protein diet induces lipid metabolism disorders in late-phase laying hens. Reducing energy levels in the low-protein diet to adjust the energy-to-protein ratio may improve fat deposition, but this also decreases the laying performance of hens. This study investigated the mechanism by which different energy levels in the low-protein diet influences liver lipid metabolism in late-phase laying hens through the enterohepatic axis to guide feed optimization and nutrition strategies. A total of 288 laying hens were randomly allocated to the normal-energy and normal-protein diet group (positive control: CK) or 1 of 3 groups: low-energy and low-protein diet (LL), normal-energy and low-protein diet (NL), and high-energy and low-protein diet (HL) groups. The energy-to-protein ratios of the CK, LL, NL, and HL diets were 0.67, 0.74, 0.77, and 0.80, respectively. Results: Compared with the CK group, egg quality deteriorated with increasing energy intake in late-phase laying hens fed low-protein diet. Hens fed LL, NL, and HL diets had significantly higher triglyceride, total cholesterol, acetyl-CoA carboxylase, and fatty acid synthase levels, but significantly lower hepatic lipase levels compared with the CK group. Liver transcriptome sequencing revealed that genes involved in fatty acid beta-oxidation (ACOX1, HADHA, EHHADH, and ACAA1) were downregulated, whereas genes related to fatty acid synthesis (SCD, FASN, and ACACA) were upregulated in LL group compared with the CK group. Comparison of the cecal microbiome showed that in hens fed an LL diet, Lactobacillus and Desulfovibrio were enriched, whereas riboflavin metabolism was suppressed. Cecal metabolites that were most significantly affected by the LL diet included several vitamins, such as riboflavin (vitamin B2), pantethine (vitamin B5 derivative), pyridoxine (vitamin B6), and 4-pyridoxic acid. Conclusion: A lipid metabolism disorder due to deficiencies of vitamin B2 and pantethine originating from the metabolism of the cecal microbiome may be the underlying reason for fat accumulation in the liver of late-phase laying hens fed an LL diet. Based on the present study, we propose that targeting vitamin B2 and pantethine (vitamin B5 derivative) might be an effective strategy for improving lipid metabolism in late-phase laying hens fed a low-protein diet. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionAngiotensin-converting enzyme (ACE, EC 3.4.15.1) is a very important factor in the regulation of blood pressure. Also, the inhibition of ACE with natural compounds has been a very important research area in the treatment of high blood pressure. ACE was purified and characterized from sheep plasma. Molecular docking studies and the inhibition effect of thiamine, riboflavin, and captopril on ACE were investigated.Herein, ACE was purified from sheep plasma by affinity chromatography. The effect of thiamine and riboflavin on ACE was researched. Molecular docking studies were performed to understand the molecular interactions between thiamine, riboflavin, and captopril with ACE.The purification coefficient was found to be 8636 fold. The binding energy of thiamine, riboflavin, and captopril was found to be -6.7 kcal/mol, -8.1 kcal/mol, and -5.5 kcal/mol, respectively. Thiamine conformed to three conventional hydrogen bonds with ASP:415, HIS:513, and LYS:454. Riboflavin formed four conventional hydrogen bonds with GLN:281, GLU:376, THR:282, and TYR:520. Captopril formed two conventional hydrogen bonds with ARG:124, one conventional hydrogen bond with TYR:62 and ASN:85, and one carbon-hydrogen bond with ASN:66. Molecular docking results showed that thiamine, riboflavin, and captopril interacted with ACE through hydrogen bonding and hydrophobic interactions. Thiamine and riboflavin indicated significant inhibition effects on ACE. The IC50 values of thiamine, riboflavin, and captopril were found as 960.56 µM, 11.02 µM, and 1.60 nM, respectively. Ki values for thiamine, riboflavin, and captopril were determined as 1352.04 µM, 12.30 µM, and 1.06 nM, respectively.In this work, it was concluded that thiamine and riboflavin may have preventive and therapeutical impacts against high blood pressure with their ACE inhibitor effect. Thiamine and riboflavin showed a lower inhibitory effect with a higher IC50 than captopril. However, when the inhibitory effect of thiamine and riboflavin vitamins is compared to captopril, it is concluded that they may be natural inhibitors with fewer side effects. [ABSTRACT FROM AUTHOR]

Levulinic acid, a hydrolysis product of lignocellulose, can be metabolized into important compounds in the field of medicine and pesticides by engineered strains of Saccharomyces cerevisiae. Levulinic acid, as an intermediate product widely found in the conversion process of lignocellulosic biomass, has multiple applications. However, its toxicity to Saccharomyces cerevisiae reduces its conversion effciency, so screening Saccharomyces cerevisiae genes that can tolerate levulinic acid becomes the key. By creating a whole-genome knockout library and bioinformatics analysis, this study used the phenotypic characteristics of cells as the basis for screening and found the HMX1 gene that is highly sensitive to levulinic acid in the oxidative stress pathway. After knocking out HMX1 and treating with levulinic acid, the omics data of the strain revealed that multiple affected pathways, especially the expression of 14 genes related to the cell wall and membrane system, were significantly downregulated. The levels of acetyl-CoA and riboflavin decreased by 1.02-fold and 1.44-fold, respectively, while the content of pantothenic acid increased. These findings indicate that the cell wall-membrane system, as well as the metabolism of acetyl-CoA and riboflavin, are important in improving the resistance of Saccharomyces cerevisiae to levulinic acid. They provide theoretical support for enhancing the tolerance of microorganisms to levulinic acid, which is significant for optimizing the conversion process of lignocellulosic biomass to levulinic acid. [ABSTRACT FROM AUTHOR]

Lung cancer is a malignant tumor with highly heterogeneous characteristics. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on lung cancer cells. However, its chemical and pharmacological profiles are not yet understood. In the present study, we aimed to reveal the mechanism of PT in treating lung cancer cells through metabolomics and network pharmacology. Metabolomic analysis of two strains of lung cancer cells treated with Pinellia ternata extracts (PTE) was used to identify differentially abundant metabolites, and the metabolic pathways associated with the DEGs were identified by MetaboAnalyst. Then, network pharmacology was applied to identify potential targets against PTE-induced lung cancer cells. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape. PTE obviously inhibited the proliferation, migration and invasion of A549 and NCI-H460 cells. The results of the cellular metabolomics analysis showed that 30 metabolites were differentially expressed in the lung cancer cells of the experimental and control groups. Through pathway enrichment analysis, 5 metabolites were found to be involved in purine metabolism, riboflavin metabolism and the pentose phosphate pathway, including D-ribose 5-phosphate, xanthosine, 5-amino-4-imidazolecarboxyamide, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Combined with network pharmacology, 11 bioactive compounds were found in PT, and networks of bioactive compound–target gene–metabolic enzyme–metabolite interactions were constructed. In conclusion, this study revealed the complicated mechanisms of PT against lung cancer. Our work provides a novel paradigm for identifying the potential mechanisms underlying the pharmacological effects of natural compounds. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To present baseline characteristics and to present the perioperative corneal thickness during corneal crosslinking (CXL) treatment for progressive keratoconus and to describe how the addition of sterile water (SW) efficaciously can maintain the corneal thickness. The treatment efficacy will be evaluated when the 1‐year follow‐up is complete.A randomised clinical study using epithelium‐off CXL with continuous UVA irradiation (9 mW/cm2) and two kinds of riboflavin solutions: (i) isoosmolar dextran‐based riboflavin (n = 27) and (ii) hypoosmolar dextran‐free riboflavin (n = 27). Inclusion criteria: progressive keratoconus with an increase in maximum keratometry value (Kmax) of 1.0 dioptre (12 months) or 0.5 dioptres (6 months). Corneae thinner than 400 μm were also included. Outcome parameters: Perioperative corneal thickness and the effect of adding SW.Seventy‐four per cent of the patients in the isoosmolar group and 15% in the hypoosmolar group required the addition of SW, which effectively maintained a corneal thickness of 400 μm in all cases during CXL. The addition of SW was primarily needed during the irradiation procedure and not the preoperative soaking period.Especially during the CXL irradiation phase, isoosmolar riboflavin causes a significant dehydrating effect leading to corneal thinning during CXL. The customised addition of SW is efficacious in maintaining the corneal thickness during CXL and could increase the safety of the procedure. [ABSTRACT FROM AUTHOR]

Infections caused by multidrug-resistant (MDR) bacteria have become a major challenge for global healthcare systems. The search for antibacterial compounds from plants has received increasing attention in the fight against MDR bacteria. As a medicinal and edible plant, Lophatherum gracile Brongn. (L. gracile) has favorable antibacterial effect. However, the main antibacterial active compound and its antimicrobial mechanism are not clear. Here, our study first identified the key active compound from L. gracile as luteolin. Meanwhile, the antibacterial effect of luteolin was detected by using the broth microdilution method and time-kill curve analysis. Luteolin can also cause morphological structure degeneration and content leakage, cell wall/membrane damage, ATP synthesis reduction, and downregulation of mRNA expression levels of sulfonamide and quinolones resistance genes in multidrug-resistant Escherichia coli (MDR E. coli). Furthermore, untargeted UPLC/Q-TOF-MSbased metabolomics analysis of the bacterial metabolites revealed that luteolin significantly changed riboflavin energy metabolism, bacterial chemotaxis cell process and glycerophospholipid metabolism of MDR E. coli. This study suggests that luteolin could be a potential new food additive or preservative for controlling MDR E. coli infection and spread. [ABSTRACT FROM AUTHOR]

To compare the impact of nanoselenium and sodium selenite on the performance, blood indices, and milk metabolites of dairy cows during the peak lactation period, two groups of dairy cows under the same conditions were selected as the control group (CON group) and treatment group (NSe group) for a 38- day (10 days for adaptation and 28 days for sampling) experiment. The control group (CON) was provided a basal diet +3.3 g/d of sodium selenite (purity1%), whereas the nanoselenium group (NSe) was offered the same diet +10 mL/d of nanoselenium (selenium concentration 1,500 mg/L). The results showed that NSe significantly increased the milk yield, milk selenium content, and feed efficiency (p < 0.05), but had no significant effect on other milk components (p > 0.05). NSe significantly increased blood urea nitrogen (BUN) and alkaline phosphatase (ALP) (p < 0.05), but had no significant effects on malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), blood total antioxidant capacity (T-AOC), or blood selenium (p > 0.05). In addition, the nontargeted metabolomics of the milk was determined by LC--MS technology, and the differentially abundant metabolites and their enrichment pathways were screened. According to these findings, NSe considerably increased the contents of cetylmannoside, undecylenoic acid, 3-hydroxypentadecanoic acid, 16-hydroxypentadecanoic acid, threonic acid, etc., but decreased the contents of galactaric acid, mesaconic acid, CDP-glucose etc. Furthermore, the enriched metabolic pathways that were screened with an impact value greater than 0.1 included metabolism of niacin and niacinamide, pyruvate, citrate cycle, riboflavin, glycerophospholipid, butanoate and tyrosine. Pearson correlation analysis also revealed a relationship between different milk metabolites and blood selenium, as well as between milk selenium and blood biochemical indices. In conclusion, compared with sodium selenite, nanoselenium improves the milk yield, feed efficiency, and milk selenium content of dairy cows and regulates milk metabolites and related metabolic pathways in Holstein dairy cows during the peak lactation period, which has certain application prospects in dairy production. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder potentially linked to gut dysbiosis. This comparative cross-sectional study profiled the gut microbiota in 24 treatment-naïve Thai children diagnosed with ADHD and 24 healthy ones matched by age and gender (median age: 7 years). Fecal microbial compositions were genetically analyzed using 16s rRNA gene amplicon sequencing. The study findings indicated no statistically significant differences in microbial diversity between groups, although Firmicutes and Actinobacteria appeared dominant in both groups. Moreover, ADHD patients exhibited enrichment in Alloprevotella, CAG-352, Succinivibrio, and Acidaminococcus genera, while healthy controls had higher levels of Megamonas, Enterobacter, Eubacterium hallii, and Negativibacillus genera. Spearman correlation analysis demonstrated a significant positive association between CAG-352 and inattention and hyperactivity/impulsivity scores, whereas the Eubacterium hallii group and Megamonas exhibited negative correlations with these symptomatology domains. Beta-carotene intake was associated with the Eubacterium hallii group and Succinivibrio: likewise, vitamin B2 intake was associated with Alloprevotella. Additional research should aim to elucidate the underlying mechanisms influencing clinical biomarkers that signify alterations in specific gut microbiome profiles linked to ADHD. [ABSTRACT FROM AUTHOR]

Healthcare professionals are consistently bombarded with conflicting messages about the role of diet in bone health. Yet, few resources are available that compile the broad scope of dietary factors that influence bone health. This article evaluates the evidence on the association of diet and exercise with bone health, with the aim to provide a resource for healthcare professionals and researchers in the field. This review also highlights gaps in knowledge, provides dialogue around why some studies exhibit conflicting outcomes, and showcases why many remaining questions likely cannot be answered with the current evidence to date. The best evidence to date supports obtaining recommended dairy and calcium intakes for building bone in early life and mitigating bone loss with age. However, nutrients do not solely work in isolation, and there is growing evidence that many other nutrients and dietary bioactives play a synergistic role in supporting bone health. Large randomized controlled trials, particularly in traditionally underserved subpopulations (eg, people of color, transgender individuals, older adults, etc), are needed to fully elucidate the effects of diet and exercise on bone health across the lifespan. [ABSTRACT FROM AUTHOR]

A composite is a material in which more than one metal salt or polymer can be mixed to enhance the processed product's physical and chemical properties. Due to their high band gap and enhanced excitation energy, composites can be used in numerous areas, such as solar cells, fuel cells, catalysts, and energy storage. Over a large area of applications in different fields, few studies have examined the ability of composites to sense the efficiency of riboflavin/vitamin B2. The present work explores the utilisation of trimetallic-based nanocomposite nanoparticles (TMNCsNPs) as a sensing material, which is synthesised and characterised in detail. The TMNCsNPs were used to understand the exposure of riboflavin to glassy carbon electrodes (GCE). Several electrochemical parameters were selected for the electrochemical study of the processed sensor. Initially, a long-range concentration of riboflavin (0.976–125 μM in PBS) was selected to check the efficiency of the produced sensor (TMNCsNPs/GCE). Low-to high-potential windows (0.5–15 mV/s) were chosen to measure the effect on TMNCsNPs/GCE in PBS. The chronoamperometry (CA) responses were analysed at different time intervals (0–900 s). The cyclic response (CR) was analysed for TMNCsNPs/GCE sensor for up to one month. The interference of metal was examined, and real sample analysis was also conducted and discussed with possible mechanism. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: More than 350,000 chemicals make up the chemical universe that surrounds us every day. The impact of this vast array of compounds on our health is still poorly understood. Manufacturers are required to carry out toxicological studies, for example on the reproductive or nervous systems, before putting a new substance on the market. However, toxicological safety does not exclude effects resulting from chronic exposure to low doses or effects on other potentially affected organ systems. This is the case for the microbiomeimmune interaction, which is not yet included in any safety studies. Methods: A high-throughput in vitro model was used to elucidate the potential effects of environmental chemicals and chemical mixtures on microbiomeimmune interactions. Therefore, a simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species was cultured in vitro in a bioreactor that partially mimics intestinal conditions. The bacteria were continuously exposed to mixtures of representative and widely distributed environmental chemicals, i.e. bisphenols (BPX) and/or per- and polyfluoroalkyl substances (PFAS) at concentrations of 22 μM and 4 μM, respectively. Furthermore, changes in the immunostimulatory potential of exposed microbes were investigated using a co-culture system with human peripheral blood mononuclear cells (PBMCs). Results: The exposure to BPX, PFAS or their mixture did not influence the community structure and the riboflavin production of SIHUMIx in vitro. However, it altered the potential of the consortium to stimulate human immune cells: in particular, activation of CD8+ MAIT cells was affected by the exposure to BPX- and PFAS mixtures-treated bacteria. Discussion: The present study provides a model to investigate how environmental chemicals can indirectly affect immune cells via exposed microbes. It contributes to the much-needed knowledge on the effects of EDCs on an organ system that has been little explored in this context, especially from the perspective of cumulative exposure. [ABSTRACT FROM AUTHOR]

In the field of wound healing treatment, the development of new materials is essential to cover multiple functions, such as acceleration of the healing process, prevention of infection and response to stimuli, especially if they present lower costs or are easier to manufacture. These properties are of great importance to prompt skin cicatrization. In this work, new multifunctional skin dressings for wound healing and infection prevention are developed based on new hydrogel materials. The dressings are produced via a straightforward and environmentally friendly one‐pot photopolymerization manufacturing process utilizing vitamin B2 aqueous solutions as sensitizer, and energy‐efficient blue light sources. These dressings exhibit a high swelling capacity, pH and temperature responsiveness, biocompatibility, antimicrobial activity in the absence of conventional antibiotics, and are capable of promoting wound healing. The formulation is based on the combination of three monomers: 2‐((methacryloyloxy)ethyl)trimethylammonium chloride, methacrylic acid and N‐vinyl caprolactam. Collagen, hyaluronic acid, and essential oil of hop are added to enhance antimicrobial properties and stimulate regenerative cellular processes. In vivo experiments have demonstrated that pristine dressings are superior in promoting collagen and fibroblast regeneration and accelerating cicatrization as compared to dressings containing natural products. The dressing embedded with hop also displayed antimicrobial characteristics. The preparation and testing of these new efficient wound dressings are described. This study is distinctive in its integration of environmentally conscious manufacturing techniques with innovative material formulations, resulting in superior wound dressings that are both cost‐effective and highly functional. By achieving enhanced healing and infection prevention without the employment of conventional antibiotics, this work represents a substantial advancement in sustainable and effective wound care management. [ABSTRACT FROM AUTHOR]

Abstract Riboflavin transporter deficiency (RTD) is a genetic disorder of reduced riboflavin (vitamin B2) uptake that causes progressive, multifocal neurological dysfunction. Most patients present in early childhood; if patients present later in life, symptoms usually develop more gradually. We report three previously healthy young adults, who developed rapidly progressive neurological symptoms after decreasing dietary intake of meat and dairy. After a diagnostic odyssey, the diagnosis of a riboflavin transporter deficiency was made. Treatment with high dose oral riboflavin (20–40 mg/kg/day) partially reversed symptoms. This case series highlights that reduced riboflavin intake as a result of dietary changes can unmask RTD at a later age. We emphasize the importance of early recognition of this progressive and potentially lethal disease and show that timely treatment with high dose riboflavin is highly effective.

The article titled "Correction" in the Annals of Medicine discusses corrections made to a previously published study on the nutritional status of German omnivores, vegetarians, and vegans. The corrected data shows that supplemented vegans have adequate vitamin B12 status. The article emphasizes the importance of accurate reporting in scientific research. Additionally, the given text provides data on supplement intake among the three dietary groups, but does not provide information on the effectiveness or necessity of these supplements. The table in the text presents laboratory measurements for the three dietary groups, which can be useful for library patrons researching the health effects of different diets. [Extracted from the article]

Alterations of the microbiota-gut-brain axis has been associated with intestinal and neuronal inflammation in Parkinson's disease (PD). The aim of this work was to study some mechanisms associated with the neuroprotective effect of a combination (MIX) of lactic acid bacteria (LAB) composed by Lactiplantibacillus plantarum CRL2130 (riboflavin overproducing strain), Streptococcus thermophilus CRL808 (folate producer strain), and CRL807 (immunomodulatory strain) in cell cultures and in a chronic model of parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in aged mice, and under levodopa-benserazide treatment. In vitro, N2a differentiated neurons were exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or with conditioned media from BV-2 cells exposed to the bacterial extracts. In vivo, motor skills, tyrosine hydrolase (TH) in brain and cytokine concentrations in serum and in brain were evaluated. The study of the faecal microbiota and the histology of the small intestine was also performed. The results showed that the neuroprotective effect associated with LAB MIX administration did not interfere with levodopa-benserazide treatment. This effect could be associated with the antioxidant and immunomodulatory potential of the LAB selected in the MIX, and was associated with the significant improvement in the motor tests and a higher number of TH + cells in the brain. In addition, LAB MIX administration was associated with modulation of the immune response. LAB administration decreased intestinal damage with an increase in the villus length /crypt depth ratio. Finally, the administration of the LAB MIX in combination with levodopa-benserazide treatment was able to partially revert the intestinal dysbiosis observed in the model, showing greater similarity to the profiles of healthy controls, and highlighting the increase in the Lactobacillaceae family. Different mechanisms of action would be related to the protective effect of the selected LAB combination which has the potential to be evaluated as an adjuvant for conventional PD therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. Methods From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. Results The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. Conclusions Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases. NCOMMS-23-46799C Keratoconus can be effectively stabilized by corneal crosslinking (CXL), but the depletion of stromal oxygen limits the efficiency of CXL photochemical reactions. Here the authors address this issue by developing biocompatible graphitic carbon nitride quantum dots- based oxygen self-sufficient platforms. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. Methods: Here, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm). Results: We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M− 1.S− 1. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2. Since schistosomes are damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case; covalently bound FAD on IL-4I1 appears inaccessible to SmNPP5. We also report that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM and Kcat/Km of 1393 ± 347 M− 1.S− 1. Conclusions: The sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes. [ABSTRACT FROM AUTHOR]