Search Results (301)

The reformulation of cookies using alternative flours and structured lipid systems represents a promising strategy for improving their nutritional profile. The present study characterized the dough properties, baking behavior, compositional attributes, and 48-day storage physicochemical and textural stability of cookie formulations combining mesquite or wheat flour with varying proportions of shortening and monoglyceride-based oleogel. A multifaceted modeling and temporal analysis approach was employed to assess the impact of flour type, fat blend, and storage duration on critical physicochemical variables. The findings of the study indicated that the type of flour was the predominant factor influencing moisture retention, ash content, and the rate of bake loss. In contrast, the fat blend was found to regulate oil migration and dough mechanical parameters. Oleogel-rich systems demonstrated superior stability over time, as evidenced by a diminished color change and a decelerated textural hardening process in comparison to conventional shortening controls. Concurrently, these systems maintained water activity levels below the established microbiological safety thresholds. Sensory analysis demonstrated that oleogels effectively replicated the mouthfeel and acceptability of conventional fats, exhibiting comparable hardness and crunchiness to traditional formulations. However, mesquite flour-rich formulations exhibited higher bitterness and lower adhesiveness. These findings demonstrate that oleogel incorporation provides a viable strategy for mitigating textural staling and improving lipid profiles of cookies. Full article

The Na⁺/I⁻ symporter (NIS) is the plasma membrane (PM) protein that actively mediates iodide (I⁻) transport into the thyroid gland. Pathogenic variants in the SLC5A5 gene cause iodide transport defects (ITDs). A heterozygous G288S NIS variant was identified in a Spanish family in which female carriers developed thyroid dysfunction during pregnancy. Here, we characterized the functional significance of the G288S variant and other substitutions at residue 288 of human NIS. Human NIS (hNIS) expression and maturation were analyzed by immunoblotting, its subcellular localization was analyzed by immunofluorescence and flow cytometry, and its activity was analyzed by radioiodide uptake assays. The G288S variant does not affect hNIS maturation, membrane trafficking, or I⁻ uptake capacity, but significantly reduces I⁻ affinity while preserving substantial transport activity. In contrast, substitutions introducing charged residues (arginine, aspartic acid, or glutamic acid) or proline severely disrupted NIS maturation, plasma membrane targeting, and iodide transport. Because the variant was identified in heterozygosity, we evaluated residue 288 substitutions under heterozygous-like conditions. Co-expression of the patient-derived G288S variant with WT NIS produced an intermediate apparent K_m without reducing V_max compared with WT, consistent with a modest co-expression-dependent kinetic effect rather than a strong dominant-negative mechanism. In contrast, the severely disruptive G288E substitution reduced cell-surface NIS expression under co-expression conditions, providing proof-of-principle evidence that severe alteration of residue 288 can impair NIS plasma membrane delivery. These findings highlight residue 288 as a key determinant of hNIS functionality and underscore the need to carefully evaluate heterozygous SLC5A5/NIS variants, as they may become clinically relevant under conditions of increased physiological iodine demand and contribute to partial iodide transport impairment. Full article

Background/Objectives: Acute myeloid leukemia (AML) is a hematological malignancy frequently driven by mutations in the FLT3 gene, particularly internal tandem duplications (FLT3-ITD), which contribute to aberrant cell proliferation and resistance to tyrosine kinase inhibitors (FLT3i). The limitations of current FLT3i therapies, including drug resistance, off-target effects, and poor selectivity, necessitate the development of novel therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) represent a promising approach to achieving degradation of oncogenic proteins. Methods: We developed FLT3-targeting PROTACs based on the previously described compound MA49, with a focus on linker modifications to improve degradation efficiency and pharmacokinetic properties. Results: Among these, compounds MA190 and MA191, containing rigid cyclohexyl-piperidine/piperazine linkers, demonstrate superior degradation of FLT3-ITD in MV4-11 AML cells at nanomolar concentrations, achieving >95% reduction in FLT3-ITD levels, outperforming MA49. In addition to improved kinase selectivity, good solubility, and plasma stability, MA190 and MA191 also exhibit excellent metabolic stability, whereas the predecessor PROTAC MA49 was unstable in microsomal assays. In cellular assays, MA190 and MA191 induce potent apoptosis in FLT3-ITD⁺ AML cells but have minimal effects on cells with wild-type FLT3. Proteomics reveal that MA191 also degrades MAPK14 (p38α), a kinase upregulated in leukemia, in addition to FLT3. Conclusions: Dual targeting of FLT3-ITD and MAPK14 enhances proapoptotic signaling without any cytotoxic effect on normal human HEK293 cells. The co-inhibition using MA191 or a combination of doramapimod (a MAPK14 inhibitor) with a non-degrading FLT3 inhibitor result in greater caspase-3 activation than either treatment alone. This synergistic effect can be a therapeutic advantage, as several oncogenic drivers are switched off simultaneously by MA191. Full article

Airfield lighting control (ALC) is critical for ensuring safe, efficient, and compliant airport operations, especially under low-visibility conditions. However, current centralized control architectures cannot adequately meet the real-time responsiveness, scalability, and reliability requirements of Advanced Surface Movement Guidance and Control Systems (A-SMGCS) Level IV. To overcome these limitations, this paper proposes a novel cloud–edge–end collaborative architecture for a mobile ALC scenario, in which we formulate a joint task computing and energy consumption optimization problem to maximize long-term system utility under latency, computation, and communication constraints. In this way, the mobile airfield lighting (MAL) system can also quickly adapt its optimal formation pattern based on the airport environment, lighting conditions, and the type of aircraft taking off or landing via efficient computation, thereby achieving the best navigational assistance effect. For solving such an optimization problem, a framework that combines K-medoids with the Improved Twin Delayed Deep Deterministic Policy Gradient (ITD3) is proposed to integrate the efficiency of clustering for rough allocation and the high-precision dynamic optimization capability of the improved TD3. The training depends on edge nodes and the cloud to achieve online performance. Finally, the extensive simulation proved that our novel algorithm is efficient. Full article

Urban areas across Europe are undergoing rapid morphological transformations driven by densification, redevelopment, and infrastructure expansion. Monitoring these urban changes requires operational, harmonized, and reproducible approaches grounded in Earth Observation. This study presents a Copernicus use case demonstrating how the High-Resolution Layer Imperviousness Change (2015–2018) and Urban Atlas datasets can be integrated with the Guidos Toolbox (GTB) to quantify structural urban change across six metropolitan areas (Milan, Sofia, Riga, Warsaw, Viseu, Santander). Morphological Spatial Pattern Analysis (MSPA) and entropy-based indicators were applied to characterize land take, fragmentation, compaction, and internal reorganization of impervious surfaces. The combined framework captured both configurational morphology and spatial disorder, revealing divergent development patterns: pronounced heterogeneity and fragmentation in Sofia, stabilization or compact growth in Milan, Warsaw, and Santander, controlled densification in Riga, and localized intensification without outward expansion in Viseu. All analyses rely on openly accessible Copernicus data and open-source tools, ensuring full reproducibility and transferability. Outputs were disseminated through a FAIR-compliant geoportal developed within a Copernicus FPCUP project, supporting transparency and reuse. The findings underscore the value of Copernicus services for operational urban monitoring and provide a scalable methodology to support European land-use policies, including the Zero Net Land Take 2050 target and the EU Soil Strategy. Full article

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy. AML classification is currently based on cytogenetic and molecular alterations as well as immunophenotyping, although risk stratification still relies primarily on cytogenetic findings. However, approximately 45% of AML patients present with a normal karyotype, which makes accurate risk classification and treatment stratification more challenging. Therefore, the identification of molecular prognostic markers described in the literature has become essential in routine diagnostic laboratories, enabling the more precise categorization of patients into risk groups. In this study, we present a simple, rapid, step-by-step multiplex PCR protocol combined with capillary electrophoresis for the detection of two of the most prevalent molecular alterations in AML: nucleophosmin 1 (NPM1) mutations and Fms-like tyrosine kinase 3 internal tandem duplications (FLT3/ITD). This protocol provides a practical workflow that can assist diagnostic laboratories in implementing and optimizing multiplex mutation detection in routine practice. Full article

Patents are essential carriers of technological innovation, and their efficient transfer is critical for accelerating technological iteration in the lithium battery industry and supporting sustainability in the new energy sector. However, existing patent recommendation methods lack frameworks for handling heterogeneous enterprise demands, which limits the accuracy of supply–demand matching. This study proposes a knowledge graph-based differentiated patent recommendation framework for enterprise technological demands in the lithium battery domain. A five-element content framework—material, method, efficacy, product, and application—is constructed from both the supply and demand sides. Enterprise demands are classified into complete and incomplete types based on element coverage, and patent supply knowledge graphs are built for potentially relevant patents. Two differentiated recommendation methods are then developed. For complete demands, the Precision Recommendation Method for Complete Technological Demands integrates BERT-based semantic encoding, TransE-based structural modeling, and RAG-based constraint retrieval to achieve precise matching under full element coverage. For incomplete demands, the Fuzzy Recommendation Method for Incomplete Technological Demands incorporates multi-source enterprise data to enrich demand categories and constructs augmented query contexts to generate diversified candidate patent sets. Empirical validation based on 25 demand-driven patent transfer cases shows that the PR-CTD method exactly identifies the actual transferred patents in three cases. The FR-ITD method ranks 6 out of 14 actual transferred patents within the Top-5 results, while the remaining cases are all within the Top 13. These results demonstrate the effectiveness of the proposed framework in real-world patent transfer scenarios. This study provides a novel theoretical perspective for the structured modeling of heterogeneous technological demands and supply–demand semantic matching. It also offers practical value by improving the efficiency of patent retrieval and matching, thereby supporting patent technology transfer in the lithium battery industry. Full article

The global increase in metabolic syndrome, characterized by the dysregulation of carbohydrate and lipid metabolism accompanied by oxidative stress and chronic inflammation, has driven research into plant species rich in polyphenols capable of modulating these pathophysiological mechanisms. Mexican species of the genus Arbutus represent a potential source of phenolic compounds with functional relevance; however, they remain poorly explored phytochemically and biologically. The present study aimed to characterize the phytochemical profile and evaluate the biological activity of 1% (w/v) leaf infusions of A. bicolor, A. tessellata, A. madrensis, A. arizonica, and A. occidentalis. Proximal analyses, spectrophotometric determinations of total phenols, flavonoids, and proanthocyanidins, as well as characterization by UPLC–ESI–MS/MS were performed. In vitro antioxidant, anti-inflammatory, and digestive enzyme inhibitory activities were also evaluated. Proximate analysis revealed that carbohydrates constituted the predominant component (72–82%), followed by lipids (3–12%), proteins (4–8%), ash (3–5%), and moisture (5–6%). The total phenolic content ranged from 25.39 to 64.14 mg EAG, being A. occidentalis the species with the highest concentration, while total flavonoids ranged from 14.91 to 33.33 mg EC per gram of dry weight. A total of 38 phenolic compounds were identified, exhibiting marked interspecific variability. A. occidentalis, distinguished by its high ellagitannin content, exhibited the highest antioxidant capacity (ORAC: 10.40 mM TEAC/g) and notable erythrocyte membrane stabilization (~69%). Enzymatic inhibition demonstrated differential profiles: A. tessellata showed the most significant inhibition of α-amylase (80.19%), whereas A. bicolor exhibited higher inhibition of α-glucosidase (81.88%) and pancreatic lipase (74.26%) could be associated with stilbenes such as resveratrol. Bioactivity was more strongly associated with the specific phytochemical profile than with total phenolic content. These findings suggest that Arbutus spp. leaf infusions may represent multifunctional phytochemical matrices with potential relevance in metabolic syndrome management. Full article

The FLT3-ITD mutation is a critical prognostic marker in acute myeloid leukemia (AML) and recent clinical trials demonstrate that FLT3-based measurable residual disease (MRD) is both prognostic and predictive, guiding therapeutic interventions in intensive and post-transplant settings. Conventional detection methods lack the sensitivity required for effective MRD monitoring. We developed a patient-specific droplet digital PCR (ddPCR) approach achieving analytical sensitivity of 10⁻⁵ (0.001%) for FLT3-ITD quantification. In our cohort, ddPCR enabled longitudinal monitoring of clonal dynamics, allowing the detection of re-emerging FLT3-ITD clones months before hematologic relapse and earlier than standard capillary electrophoresis. Notably, 25% of patients who relapsed as FLT3-ITD positive despite being classified as FLT3-negative at diagnosis harbored detectable microclones when retrospectively analyzed by ddPCR, suggesting that FLT3-ITD-positive relapse frequently originates from pre-existing subclones below conventional detection thresholds. These findings challenge current diagnostic classification and may influence risk stratification and treatment decisions, particularly regarding FLT3 inhibitor eligibility. While ddPCR is limited to tracking known dominant clones, it represents a practical, cost-effective solution for high-sensitivity MRD surveillance. In the era of targeted FLT3 therapies, integrating sensitive molecular monitoring into routine AML management may enable timely therapeutic adjustments and improve patient outcomes. Full article

Background/Objectives: The emergence of FLT3 inhibitors (FLT3i) has radically transformed the prognostic and therapeutic landscape for FLT3-mutated Acute Myeloid Leukemia, stimulating the need for comprehensive and structured clinical guidance. Methods: We aimed to develop evidence-based recommendations spanning the entire disease continuum of FLT3-mutated AML from leading Italian experts through a modified Delphi consensus process. Results: The panel achieved a high degree of agreement on specific interventions covering diagnostic testing, upfront FLT3i integration, role of allogeneic hematopoietic cell transplantation (allo-HSCT), Minimal Residual Disease (MRD) monitoring, and relapsed/refractory (R/R) strategies. Key recommendations mandate that analysis for both FLT3-ITD and FLT3-TKD mutations is required at diagnosis, with capillary electrophoresis or NGS as preferred methods. All fit patients with FLT3m-AML must receive intensive chemotherapy plus a FLT3i (midostaurin or quizartinib) and be evaluated for allo-HSCT. For unfit patients, the current standard of HMA + venetoclax is considered suboptimal, making the search for alternative strategies imperative. MRD monitoring using available molecular or flow cytometry markers is recommended to assess relapse risk and to optimize the allo-HSCT strategy. In the R/R setting, retesting the FLT3 status is mandatory, and gilteritinib is the standard treatment, serving as a bridge-to-transplant and for post-HSCT maintenance. Conclusions: The integration of FLT3i has shifted FLT3m-AML into a more favorable intermediate prognostic category, enhancing the role of curative strategies like allo-HSCT. This consensus paper provides a structured evidence-based comprehensive guide, translating complex data into clear actionable clinical recommendations that minimize practice variability and ultimately optimize management for this high-risk population. Full article

Critical thinking (CT) is essential for navigating the complex socio-scientific issues in contemporary biomedicine. These issues cross disciplinary boundaries and involve multiple societal stakeholders. Interdisciplinary and transdisciplinary (ITD) education therefore provides a valuable context for developing CT by confronting students with diverse forms of knowledge and prompting reflection on their disciplinary assumptions. In this study, boundary crossing is used as a pedagogical framework, with a focus on identification (understanding alternative perspectives) and reflection (examining one’s own assumptions). We examine how such ITD education can foster CT by enhancing students’ appreciation of disciplinary and societal viewpoints. Data from a pre- and post-course assignment were analyzed using a convergent mixed-methods approach. Students ranked the relevance and effectiveness of sessions engaging with different perspectives and identified educational design elements that contributed to broadening their biomedical outlook. Findings indicate shifts in how students perceived the relevance of different perspectives. Particularly, appreciation of the legal perspective increased. Sessions were considered most effective when involving interaction with perspective owners, interactive learning methods, and clear instructional design. The results suggest that boundary-crossing pedagogies can support CT in higher education by engaging students in reflective engagement with different disciplinary and societal perspectives. Full article

Polo is a high-speed equestrian sport that imposes mechanical demands on horses and turf, yet limited research has examined the functional behavior of polo playing surfaces. This study characterizes the spatial variability of mechanical surface properties across turf polo pitches representing high-, medium-, and low-handicap categories. Three fields were assessed using lightweight field-based instruments, including the Impact Test Device (ITD), Rotational Peak Shear (RPS) tester, Going Stick© for penetration (GSP) and shear (GSS), and a TDR probe for volumetric moisture content (VMC%). A total of 210–223 grid-based sampling points per pitch were analyzed to evaluate mechanical responses under vertical and horizontal loading conditions. Significant differences among pitches were observed, with ITD and VMC emerging as the indicators of surface behaviour. Spatial analysis revealed heterogeneous within-pitch patterns, expressed as directional gradients and localized variability. Linear discriminant analysis demonstrated that the combined measurements could differentiate pitches associated with different handicap levels with high classification accuracy (0.88). Although the applied instruments do not replicate full equine biomechanical loading, they proved effective in detecting spatial variability in surface uniformity, a functional property relevant to performance and equine welfare. These findings support integration of spatially explicit surface assessments into routine turf management practices. Full article

Background/Objectives: Speech understanding in noise relies on both temporal fine structure (TFS) and temporal envelope (ENV) cues. While TFS primarily conveys interaural time differences (ITDs) at low frequencies, ENV cues can also support ITD processing, especially when TFS is unavailable or degraded. Expanding the ENV by increasing modulation depth has been proposed to improve speech perception, but its effects on spatial release from masking (SRM) and binaural temporal processing in normal-hearing listeners remain unclear. The goal of this study was to evaluate the effect of ENV enhancement on SRM in young adults with normal hearing and its influence on ITD sensitivity and interaural coherence (IC). Method: Thirty normal-hearing native Kannada speakers (19–34 years) participated. Speech stimuli consisted of Kannada sentences embedded in four-talker babble at −5, 0, and +5 dB signal to noise ratio (SNR). Target and masker were spatialized using head-related transfer functions at 0°, 15°, and 37.5° azimuths. Stimuli were presented with and without ENV enhancement (compression–expansion algorithm). Speech recognition scores were analyzed using generalized linear mixed models, and SRM was calculated as performance differences between co-located and spatially separated conditions. Cross-correlation analyses were performed to estimate ITDs and IC across SNRs. Result: ENV enhancement yielded significantly higher SRM values across all SNRs and spatial separations. Benefits were greatest at lower SNRs and wider target–masker separations. Cross-correlation analysis showed enhanced IC and more reliable ITD estimates under the expanded condition, particularly at moderate SNRs. Conclusions: Temporal ENV enhancement strengthens spatial unmasking and binaural timing cues in normal-hearing adults, especially under adverse listening conditions. These findings highlight its potential application in auditory rehabilitation and hearing technologies where ENV cues are critical. Full article

Glutamine metabolism has emerged as one of the most critical bioenergetic and biosynthetic programs sustaining leukemic cell growth, survival, stemness and therapeutic resistance. In both acute and chronic leukemias, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), malignant cells display a strong dependency on extracellular glutamine to support mitochondrial respiration, anabolic biosynthesis and redox homeostasis. This dependency is reinforced by oncogenic signaling networks, post-transcriptional metabolic regulation and microenvironmental adaptation within the bone marrow niche. Therapeutic strategies targeting glutamine utilization, including glutaminase inhibition, transporter blockade and enzymatic glutamine depletion, have demonstrated robust antileukemic activity in preclinical models, and early clinical efforts have begun to explore glutamine-directed interventions in myeloid neoplasms. However, metabolic plasticity, microenvironment-derived nutrient buffering and systemic toxicity remain significant limitations to clinical translation. This review provides a detailed synthesis of the biochemical framework of glutamine metabolism in leukemia, the molecular mechanisms enforcing glutamine addiction, the downstream functional consequences on proliferation, redox balance and leukemic stem cell biology, the current landscape of therapeutic strategies and emerging directions aimed at overcoming resistance and improving clinical efficacy. Full article

Background: The FLT3-ITD mutation is associated with a poor prognosis in acute myeloid leukemia (AML), particularly in relapsed or refractory (R/R) cases. Although Gilteritinib has been approved for the treatment of R/R AML with FLT3-ITD mutation, the emergence of resistance in clinical settings remains a major challenge. Homoharringtonine (HHT), a plant-derived alkaloid with antitumor properties, has also been used in AML treatment. However, the combination effects of HHT and gilteritinib have not been investigated. Methods: The cell viability and apoptosis of MV4-11 and MOLM-13 cells in the treatment of HHT, gilteritinib and the combination were assessed by CCK-8 assay and flow cytometry, respectively. Combination index (CI) values were calculated using CompuSyn 1.0. Western blotting was used to investigate the molecule mechanisms of HHT and gilteritinib mediated anti-leukemia effects in time- and dose-dependent experiments. To investigate the role of p53 status in drug responses, MV4-11-p53R248W and MV4-11-p53WT subclones were isolated and MV4-11-p53knockout cells was established through CRISPR/Cas9 system. The cell viability and apoptosis of MV4-11 cells with various p53 status were compared. Moreover, RNA-seq analysis was performed in MV4-11 cells treated with or without HHT. RT-qPCR and Western blotting were conducted to verify the mechanism underlying HHT-induced p53 upregulation. Results: HHT and gilteritinib exerted a significant synergistic effect on cell viability and apoptosis in MV4-11 and MOLM-13 cells, which was markedly diminished in the cells with the p53-R248W muta-tion or without p53. Mechanistically, HHT and gilteritinib both suppressed FLT3 signaling. Interestingly, HHT mediated the upregulation of p53 through HSPA8 downregulation, while gilteritinib downregulated the p53 level. The combination enhanced the p53 expression. Conclusions: Our findings elucidate the mechanism underlying this synergistic interaction and underscore the potential of p53 status as a predictive biomarker for identifying patients most likely to benefit from HHT and gilteritinib combination therapy. Full article