Advancing Open Science

Honeybee brood is a nutrient-rich food source containing natural umami-active compounds, such as glutamic acid, aspartic acid, and 5′-nucleotides, which are responsible for its characteristic umami taste. This study aimed to optimize drying conditions to enhance the umami composition and sensory properties of honeybee brood umami powder (HBb-UP). A factorial design was employed to evaluate the effects of drying temperature and time on umami-related amino acids, 5′-nucleotides, and equivalent umami concentration (EUC). Drying temperature and time significantly influenced the formation of umami compounds, with the optimized drying condition (65 °C for 3 h) promoting higher umami composition and improved sensory attributes of HBb-UP. Volatile flavor analysis using GC–MS and an electronic nose revealed a diverse range of aroma compounds contributing to the overall flavor profile. Descriptive sensory evaluation and electronic tongue analysis indicated that umami and saltiness were the dominant taste attributes, accompanied by mild seasoning and fishy notes associated with interactions between amino acids and nucleotides. Principal component analysis demonstrated positive correlations among umami-related amino acids, nucleotides, EUC, and sensory attributes, confirming their combined contribution to taste perception. These findings highlight the potential of optimized HBb-UP as a natural flavor enhancer and functional ingredient for use in sustainable food systems.

Background/Objectives: DNA-targeting small molecules that induce replication stress represent a promising strategy in anticancer drug development. 1,8-Naphthalimide (NI) derivatives are well-established DNA-intercalating agents, and heterocyclic annulation offers a rational approach to enhancing their potency and tumor selectivity. Here, we report the synthesis and biological evaluation of a novel series of benzofuran-containing naphthalimide derivatives, with particular focus on the lead dinitro-substituted compound 5d. Methods: Cytotoxic activity was assessed using the MTT assay in A549 (p53 wild-type), H1299 (p53-null), and MRC-5 cells. Long-term antiproliferative effects were evaluated by clonogenic survival assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Replication stress and DNA damage were quantified by EdU incorporation and γH2AX immunofluorescence, respectively. Apoptosis was assessed by Annexin V/PI staining and caspase-3/7 activation assay. p53 nuclear accumulation and autophagy induction were evaluated by immunofluorescence and Western blot, using LC3 as an autophagic marker. Results: All compounds exhibited cytotoxic activity in the nanomolar range, with 5d emerging as the most potent and selective. Clonogenic survival was significantly reduced, indicating durable suppression of proliferative capacity. Treatment with 5d induced G₁ arrest in A549 cells and the accumulation of H1299 cells in G₂/M, consistent with p53-dependent and p53-independent checkpoint activation, respectively. EdU incorporation was markedly reduced, while γH2AX intensity increased, collectively supporting a replication stress-driven mechanism of DNA damage. Apoptosis was confirmed by increased Annexin V-positive populations and caspase-3/7 activation. LC3 puncta formation and LC3-I/LC3-II conversion were increased, indicating LC3 processing and autophagosome accumulation consistent with the activation of autophagy-related processes. Conclusions: 5d induces a cellular phenotype consistent with replication stress, including reduced EdU incorporation, γH2AX accumulation, cell cycle arrest, and apoptotic cell death in a p53 status-dependent manner. These findings establish benzofuran-annulated naphthalimides as a promising scaffold for the development of anticancer agents that exploit replication stress vulnerabilities in tumor cells.

Wheat is a major staple crop, and storage mold growth poses a severe threat to grain safety and quality stability. Natural mold development in stored wheat exhibits subtle, localized, and highly heterogeneous characteristics. Existing unimodal methods and global fusion approaches generally suffer from insufficient local feature sensitivity, hindering fine-grained mold severity grading. To address this limitation, we propose a Mask-Guided Fine-Grained Fusion Network, a weakly supervised framework based on local RGB–HSI fusion. This framework employs a dynamic parallel A/B experimental design to construct time-matched proxy labels via weakly supervised learning. A standardized preprocessing pipeline including single-kernel extraction, foreground segmentation, and cross-modal registration is established to resolve RGB–HSI spatial misalignment, ensuring physical-level spatial consistency of multimodal features. The model incorporates a Foreground-Aware Spectral Recalibration (FASR) module to suppress background noise, a Mask-Guided Dilated Cross-modal Local Attention (MDCLA) mechanism to establish fine-grained local mappings between RGB visual phenotypes and hyperspectral responses, and a sample-level adaptive fusion strategy to dynamically weight features by modal reliability, enhancing representation of complex samples across all mold stages. Experiments show that the Mask-Guided Fine-Grained Fusion Network achieves 0.9689 classification accuracy, 0.9698 Macro-F1 score, and 0.0593 Mean Absolute Error (MAE), significantly outperforming state-of-the-art unimodal deep models and global attention fusion baselines. This work provides a proof-of-principle framework for fine-grained non-destructive mold risk assessment in stored wheat.

Melittin (Mel) is a membrane-active peptide with potential anticancer activity, but its direct therapeutic application may be limited by nonspecific toxicity and delivery-related challenges. The study aimed to assess melittin-functionalized magnetic nanoparticles (MNPs-Mel) as a strategy to enhance antitumor activity in Caco-2 cells, with/without magnetic hyperthermia (MH) association. BJ fibroblasts were used as a normal human in vitro cellular model. The effects of free Mel (2.5 µg/mL), MNPs, and MNPs-Mel (50 µg/mL both) + MH (30 min at 355 kHz and 25 kA/m) were assessed using colorimetry (for viability), luminescence (ATP), and spectrophotometry (lactate) following different exposure conditions. The mechanism of apoptosis induction was evaluated by ELISA (caspase 8 and 9 levels). Transmission electron microscopy (TEM) was also used to evaluate nanoparticle morphology and treatment-associated cellular ultrastructural changes. Free Mel reduced viability in both cell lines, with Caco-2 cells showing greater sensitivity at lower concentrations. MNPs (with/without MH) produced limited and less consistent effects, whereas MNPs-Mel significantly reduced Caco-2 viability and ATP levels and increased LDH and caspase 9. MH further enhanced the effects of MNPs-Mel: reduced viability (57–58% of the control at 24 h and 72 h), decreased ATP levels (67% of the control at 24 h and 53% at 72 h), increased LDH levels (206% of the control at 24 h and 301% at 72 h), and induced the mitochondrial apoptotic pathway (caspase 9 increased with 2164% of the control at 72 h). TEM proved the internalization of both MNPs and MNPs-Mel and revealed extensive ultrastructural alterations concerning mitochondria and lysosomes produced by MNPs-Mel, particularly in the Caco-2 cells. These modifications were heavily increased by MNPs-Mel + MH exposure. Overall, these findings demonstrate that Mel functionalization increases the antitumor activity of Mel at lower doses and that MH further potentiates this effect in Caco-2 cells.

Preterm infants, especially extremely preterm infants under 28 weeks of gestation, face high mortality rates due to respiratory distress resulting from pulmonary immaturity. Conventional mechanical ventilation and extracorporeal membrane oxygenation (ECMO) therapy inevitably cause irreversible lung injury or severe complications, respectively. Here, we developed a microfluidic oxygenator (MO) mimicking the human alveolar-capillary barrier to provide respiratory support for preterm infants. These structures promoted uniform flow distribution, reduced high-shear stress and flow stagnation, and improved gas exchange efficiency. In vitro experiments demonstrated that a single-layer MO raised blood oxygen saturation from 64.7% to 96.5% at 8 mL/min, with a corrected vol% oxygen transfer of 5.24% (52.4 mL O₂/L blood). Hemolysis and coagulation measurements after a 6 h circulation confirmed good hemocompatibility, with most blood damage attributable to the pump. An eight-layer stacked MO was configured with a total priming volume of approximately 5.6 mL and a pressure drop of 25–35 mmHg at 24–40 mL/min, indicating its potential in pumpless extracorporeal circulation for preterm neonates. This MO holds promise for providing minimally invasive and customizable respiratory support in an artificial uterus system.

Background/Objectives: This investigation was performed because corticosteroid injections are commonly used for symptomatic relief in patients with meniscal deficiency, yet their effect on graft survivorship and postoperative outcomes following meniscal allograft transplantation (MAT) remains poorly understood, with limited literature specifically addressing this topic. The aim of this study is to evaluate whether preoperative intra-articular corticosteroid injections (ICS) are associated with reoperation after MAT. Secondary aims included comparing reoperation-free survival, patient-reported outcome measures (PROMs), and patient acceptable symptom state (PASS) achievement. Methods: A retrospective review of 130 adults undergoing meniscal allograft transplantation (MAT) between 2011 and 2023 was performed. Patients with documented corticosteroid injection (CSI) status and ≥2 years of follow-up were included. Exclusion criteria included prior meniscal allograft transplantation, receipt of non-corticosteroid injections (e.g., hyaluronic acid or platelet-rich plasma), concomitant osteotomy procedures, multi-ligament knee reconstruction or inadequate follow-up. Propensity score matching (2:1 no steroid: steroid) based on age, sex, body mass index, fixation technique, operative compartment, and concomitant procedures yielded 54 matched patients (35 no steroid, 19 steroid). The primary outcome was ipsilateral knee reoperation, categorized as major reoperation (revision MAT, anterior cruciate ligament reconstruction, osteochondral allograft transplantation, conversion to total knee arthroplasty, meniscectomy and meniscus repair). Minor reoperations included irrigation and debridement, lysis of adhesions or manipulation under anesthesia, hardware removal, chondroplasty, and synovectomy. Reoperation-free survival was assessed using Kaplan–Meier analysis. PROMs and PASS were compared using adjusted regression models. Statistical significance was set at p < 0.05. Results: Baseline characteristics and follow-up were comparable between groups (7.6 ± 3.5 vs. 6.6 ± 3.2 years; p = 0.30). Overall reoperation occurred in 37.1% of patients in the no-steroid group and 31.6% in the steroid group (p = 0.771). Major reoperation rates were similar (17.1% vs. 15.8%; p = 1.000. There was no significant difference in minor reoperations between groups (20.0% vs. 10.5%; p = 0.468). Kaplan–Meier analysis demonstrated no difference in reoperation-free survival (p = 0.903), with comparable survival at the 1-, 2-, and 5-year time points. No individual subtypes differed significantly between groups. PROMs and PASS achievement were also similar, with no statistically significant differences observed. Conclusions: Preoperative corticosteroid injection was not associated with increased reoperation risk, inferior reoperation-free survival, or worse patient-reported outcomes following meniscal allograft transplantation. However, given the study’s limited power, lack of detailed injection characteristics, and the use of a heterogeneous complication outcome, these findings should be interpreted cautiously, as further investigation is warranted.

The large-scale integration of distributed photovoltaics (DPVs) into the distribution network exacerbates voltage fluctuations and substantially increases network losses. To improve the voltage quality and economic efficiency of distribution networks, a Volt/Var optimization (VVO) model is established. Coordinating multiple heterogeneous devices, the model aims to minimize the total voltage deviation, the total network losses, and the regulation cost of discrete equipment simultaneously. Considering multi-constraint coupling characteristics, a quantitative method is proposed to evaluate the reactive power regulation potential of DPVs under intricate operating conditions. Then, the multi-strategy integrated rime optimization algorithm (MSIRIME) is utilized for the model solution. Fuch chaotic mapping generates uniformly distributed and ergodic initial populations. A dual-branch search mechanism combining the snow ablation optimizer with the rime optimization significantly enhances global exploration capabilities. The guided learning strategy balances exploration and exploitation for high-dimensional VVO, preventing local optima. Case tests on a modified IEEE 33-bus system demonstrate that the proposed model exhibits excellent effectiveness and robustness. Moreover, MSIRIME exhibits better optimization performance than some classic and recently proposed strategies, reducing the average network losses and voltage deviation over 30 independent runs by at least 5.87% and 52.22%, respectively, relative to those of the compared methods.

Mycotoxins are fungal secondary metabolites with dual significance: they threaten health via food contamination yet hold potential as biopesticides. Their isolation from complex matrices remains a critical challenge. This review analyzes classical methods (liquid–liquid extraction, SPE including QuEChERS, chromatography). Traditional techniques suffer from poor selectivity, multi-step processing, large toxic solvent volumes, and matrix effects. As alternatives, emerging strategies based on rational design are considered: directed cocrystallization, supercritical fluid extraction, smart MOF/COF membranes, and AI integrated with physicochemical modeling. The concept of “precision” extraction enabling prediction of target isolation at the molecular level is developed. Recommendations for standardizing experimental reporting to create machine-readable datasets for neural networks are provided. The review concludes that while most still require experimental validation for mycotoxins, these approaches point toward selective, sustainable mycotoxin isolation technologies for analytical control and pure standard production.