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Keywords = natural product-likeness

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16 pages, 1541 KiB  
Article
A Ubiquitous Volatile in Noctuid Larval Frass Attracts a Parasitoid Species
by Chaowei Wang, Xingzhou Liu, Sylvestre T. O. Kelehoun, Kai Dong, Yueying Wang, Maozhu Yin, Jinbu Li, Yu Gao and Hao Xu
Biology 2025, 14(8), 1007; https://doi.org/10.3390/biology14081007 - 6 Aug 2025
Abstract
Natural enemies commonly probe larval bodies and frass with their antennae for prey hunting. However, the attractants to natural enemies emitted directly from hosts and host-associated tissues remained largely unknown. Here, we used two generalist noctuid species, Helicoverpa armigera (Hübner) and Spodoptera frugiperda [...] Read more.
Natural enemies commonly probe larval bodies and frass with their antennae for prey hunting. However, the attractants to natural enemies emitted directly from hosts and host-associated tissues remained largely unknown. Here, we used two generalist noctuid species, Helicoverpa armigera (Hübner) and Spodoptera frugiperda (JE Smith), along with the larval endoparasitoid Microplitis mediator (Haliday) to address the question. Extracts of larval frass of both the noctuid species were strongly attractive to M. mediator females when hosts were fed either maize, cotton, soybean leaves, or an artificial diet without leaf tissues. By using a combination of electrophysiological measurements and behavioral tests, we found that the attractiveness of frass mainly relied on a volatile compound ethyl palmitate. The compound was likely to be a by-product of host digestion involving gut bacteria because an antibiotic supplement in diets reduced the production of the compound in frass and led to the decreased attractiveness of frass to the parasitoids. In contrast, extracts of the larval bodies of both the noctuid species appeared to be less attractive to the parasitoids than their respective fecal extracts, independently of types of food supplied to the larvae. Altogether, larval frass of the two noctuid species was likely to be more important than their bodies in attracting the endoparasitoid species, and the main attractant of frass was probably one of the common metabolites of digestion involving gut microbes, and its emission is likely to be independent of host plant species. Full article
(This article belongs to the Special Issue The Biology, Ecology, and Management of Plant Pests)
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21 pages, 1353 KiB  
Article
Hydrogen Cost and Carbon Analysis in Hollow Glass Manufacturing
by Dario Atzori, Claudia Bassano, Edoardo Rossi, Simone Tiozzo, Sandra Corasaniti and Angelo Spena
Energies 2025, 18(15), 4105; https://doi.org/10.3390/en18154105 - 2 Aug 2025
Viewed by 198
Abstract
The European Union promotes decarbonization in energy-intensive industries like glass manufacturing. Collaboration between industry and researchers focuses on reducing CO2 emissions through hydrogen (H2) integration as a natural gas substitute. However, to the best of the authors’ knowledge, no updated [...] Read more.
The European Union promotes decarbonization in energy-intensive industries like glass manufacturing. Collaboration between industry and researchers focuses on reducing CO2 emissions through hydrogen (H2) integration as a natural gas substitute. However, to the best of the authors’ knowledge, no updated real-world case studies are available in the literature that consider the on-site implementation of an electrolyzer for autonomous hydrogen production capable of meeting the needs of a glass manufacturing plant within current technological constraints. This study examines a representative hollow glass plant and develops various decarbonization scenarios through detailed process simulations in Aspen Plus. The models provide consistent mass and energy balances, enabling the quantification of energy demand and key cost drivers associated with H2 integration. These results form the basis for a scenario-specific techno-economic assessment, including both on-grid and off-grid configurations. Subsequently, the analysis estimates the levelized costs of hydrogen (LCOH) for each scenario and compares them to current and projected benchmarks. The study also highlights ongoing research projects and technological advancements in the transition from natural gas to H2 in the glass sector. Finally, potential barriers to large-scale implementation are discussed, along with policy and infrastructure recommendations to foster industrial adoption. These findings suggest that hybrid configurations represent the most promising path toward industrial H2 adoption in glass manufacturing. Full article
(This article belongs to the Special Issue Techno-Economic Evaluation of Hydrogen Energy)
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21 pages, 2399 KiB  
Review
Various Approaches Employed to Enhance the Bioavailability of Antagonists Interfering with the HMGB1/RAGE Axis
by Harbinder Singh
Int. J. Transl. Med. 2025, 5(3), 35; https://doi.org/10.3390/ijtm5030035 - 2 Aug 2025
Viewed by 230
Abstract
High-mobility group box 1 (HMGB1) is a nuclear protein that can interact with a transmembrane cell surface receptor for advanced glycation end products (RAGEs) and mediates the inflammatory pathways that lead to various pathological conditions like cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders. [...] Read more.
High-mobility group box 1 (HMGB1) is a nuclear protein that can interact with a transmembrane cell surface receptor for advanced glycation end products (RAGEs) and mediates the inflammatory pathways that lead to various pathological conditions like cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders. Blocking the HMGB1/RAGE axis using various small synthetic or natural molecules has been proven to be an effective therapeutic approach to treating these inflammatory conditions. However, the low water solubility of these pharmacoactive molecules limits their clinical use. Pharmaceutically active molecules with low solubility and bioavailability in vivo convey a higher risk of failure for drug development and drug innovation. The pharmacokinetic and pharmacodynamics parameters of these compounds are majorly affected by their solubility. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. This review mainly describes various technologies utilized to improve the bioavailability of synthetic or natural molecules which have been particularly used in various inflammatory conditions acting specifically through the HMGB1/RAGE pathway. Full article
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18 pages, 2865 KiB  
Article
Physiological and Chemical Response of Urochloa brizantha to Edaphic and Microclimatic Variations Along an Altitudinal Gradient in the Amazon
by Hipolito Murga-Orrillo, Luis Alberto Arévalo López, Marco Antonio Mathios-Flores, Jorge Cáceres Coral, Melissa Rojas García, Jorge Saavedra-Ramírez, Adriana Carolina Alvarez-Cardenas, Christopher Iván Paredes Sánchez, Aldi Alida Guerra-Teixeira and Nilton Luis Murga Valderrama
Agronomy 2025, 15(8), 1870; https://doi.org/10.3390/agronomy15081870 (registering DOI) - 1 Aug 2025
Viewed by 215
Abstract
Urochloa brizantha (Brizantha) is cultivated under varying altitudinal and management conditions. Twelve full-sun (monoculture) plots and twelve shaded (silvopastoral) plots were established, proportionally distributed at 170, 503, 661, and 1110 masl. Evaluations were conducted 15, 30, 45, 60, and 75 days [...] Read more.
Urochloa brizantha (Brizantha) is cultivated under varying altitudinal and management conditions. Twelve full-sun (monoculture) plots and twelve shaded (silvopastoral) plots were established, proportionally distributed at 170, 503, 661, and 1110 masl. Evaluations were conducted 15, 30, 45, 60, and 75 days after establishment. The conservation and integration of trees in silvopastoral systems reflected a clear anthropogenic influence, evidenced by the preference for species of the Fabaceae family, likely due to their multipurpose nature. Although the altitudinal gradient did not show direct effects on soil properties, intermediate altitudes revealed a significant role of CaCO3 in enhancing soil fertility. These edaphic conditions at mid-altitudes favored the leaf area development of Brizantha, particularly during the early growth stages, as indicated by significantly larger values (p < 0.05). However, at the harvest stage, no significant differences were observed in physiological or productive traits, nor in foliar chemical components, underscoring the species’ high hardiness and broad adaptation to both soil and altitude conditions. In Brizantha, a significant reduction (p < 0.05) in stomatal size and density was observed under shade in silvopastoral areas, where solar radiation and air temperature decreased, while relative humidity increased. Nonetheless, these microclimatic variations did not lead to significant changes in foliar chemistry, growth variables, or biomass production, suggesting a high degree of adaptive plasticity to microclimatic fluctuations. Foliar ash content exhibited an increasing trend with altitude, indicating greater efficiency of Brizantha in absorbing calcium, phosphorus, and potassium at higher altitudes, possibly linked to more favorable edaphoclimatic conditions for nutrient uptake. Finally, forage quality declined with plant age, as evidenced by reductions in protein, ash, and In Vitro Dry Matter Digestibility (IVDMD), alongside increases in fiber, Neutral Detergent Fiber (NDF), and Acid Detergent Fiber (ADF). These findings support the recommendation of cutting intervals between 30 and 45 days, during which Brizantha displays a more favorable nutritional profile, higher digestibility, and consequently, greater value for animal feeding. Full article
(This article belongs to the Section Agricultural Biosystem and Biological Engineering)
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18 pages, 2892 KiB  
Review
Roles of Type 10 17β-Hydroxysteroid Dehydrogenase in Health and Disease
by Xue-Ying He, Janusz Frackowiak and Song-Yu Yang
J. Pers. Med. 2025, 15(8), 346; https://doi.org/10.3390/jpm15080346 - 1 Aug 2025
Viewed by 177
Abstract
Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain [...] Read more.
Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported km value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure km. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the ki value estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article
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23 pages, 1268 KiB  
Article
Combining Stable Isotope Labeling and Candidate Substrate–Product Pair Networks Reveals Lignan, Oligolignol, and Chicoric Acid Biosynthesis in Flax Seedlings (Linum usitatissimum L.)
by Benjamin Thiombiano, Ahlam Mentag, Manon Paniez, Romain Roulard, Paulo Marcelo, François Mesnard and Rebecca Dauwe
Plants 2025, 14(15), 2371; https://doi.org/10.3390/plants14152371 - 1 Aug 2025
Viewed by 203
Abstract
Functional foods like flax (Linum usitatissimum L.) are rich sources of specialized metabolites that contribute to their nutritional and health-promoting properties. Understanding the biosynthesis of these compounds is essential for improving their quality and potential applications. However, dissecting complex metabolic networks in [...] Read more.
Functional foods like flax (Linum usitatissimum L.) are rich sources of specialized metabolites that contribute to their nutritional and health-promoting properties. Understanding the biosynthesis of these compounds is essential for improving their quality and potential applications. However, dissecting complex metabolic networks in plants remains challenging due to the dynamic nature and interconnectedness of biosynthetic pathways. In this study, we present a synergistic approach combining stable isotopic labeling (SIL), Candidate Substrate–Product Pair (CSPP) networks, and a time-course study with high temporal resolution to reveal the biosynthetic fluxes shaping phenylpropanoid metabolism in young flax seedlings. By feeding the seedlings with 13C3-p-coumaric acid and isolating isotopically labeled metabolization products prior to the construction of CSPP networks, the biochemical validity of the connections in the network was supported by SIL, independent of spectral similarity or abundance correlation. This method, in combination with multistage mass spectrometry (MSn), allowed confident structural proposals of lignans, neolignans, and hydroxycinnamic acid conjugates, including the presence of newly identified chicoric acid and related tartaric acid esters in flax. High-resolution time-course analyses revealed successive waves of metabolite formation, providing insights into distinct biosynthetic fluxes toward lignans and early lignification intermediates. No evidence was found here for the involvement of chlorogenic or caftaric acid intermediates in chicoric acid biosynthesis in flax, as has been described in other species. Instead, our findings suggest that in flax seedlings, chicoric acid is synthesized through successive hydroxylation steps of p-coumaroyl tartaric acid esters. This work demonstrates the power of combining SIL and CSPP strategies to uncover novel metabolic routes and highlights the nutritional potential of flax sprouts rich in chicoric acid. Full article
(This article belongs to the Section Plant Physiology and Metabolism)
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43 pages, 7013 KiB  
Review
Fused-Linked and Spiro-Linked N-Containing Heterocycles
by Mikhail Yu. Moskalik and Bagrat A. Shainyan
Int. J. Mol. Sci. 2025, 26(15), 7435; https://doi.org/10.3390/ijms26157435 - 1 Aug 2025
Viewed by 186
Abstract
Fused and spiro nitrogen-containing heterocycles play an important role as structural motifs in numerous biologically active natural products and pharmaceuticals. The review summarizes various approaches to the synthesis of three-, four-, five-, and six-membered fused and spiro heterocycles with one or two nitrogen [...] Read more.
Fused and spiro nitrogen-containing heterocycles play an important role as structural motifs in numerous biologically active natural products and pharmaceuticals. The review summarizes various approaches to the synthesis of three-, four-, five-, and six-membered fused and spiro heterocycles with one or two nitrogen atoms. The assembling of the titled compounds via cycloaddition, oxidative cyclization, intramolecular ring closure, and insertion of sextet intermediates—carbenes and nitrenes—is examined on a vast number of examples. Many of the reactions proceed with high regio-, stereo-, or diastereoselectivity and in excellent, up to quantitative, yield, which is of principal importance for the synthesis of chiral drug-like compounds. For most unusual and hardly predictable transformations, the mechanisms are given or referred to. Full article
(This article belongs to the Section Macromolecules)
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22 pages, 1916 KiB  
Article
Freeze-Dried Probiotic Fermented Camel Milk Enriched with Ajwa Date Pulp: Evaluation of Functional Properties, Probiotic Viability, and In Vitro Antidiabetic and Anticancer Activities
by Sally S. Sakr and Hassan Barakat
Foods 2025, 14(15), 2698; https://doi.org/10.3390/foods14152698 - 31 Jul 2025
Viewed by 338
Abstract
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve [...] Read more.
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve this target, six FCM formulations were prepared using ABT-5 starter culture (containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus) with or without Lacticaseibacillus rhamnosus B-1937 and ADP (12% or 15%). The samples were freeze-dried, and their functional properties, such as water activity, dispersibility, water absorption capacity, water absorption index, water solubility index, insolubility index, and sedimentation, were assessed. Reconstitution properties such as density, flowability, air content, porosity, loose bulk density, packed bulk density, particle density, carrier index, Hausner ratio, porosity, and density were examined. In addition, color and probiotic survivability under simulated gastrointestinal conditions were analyzed. Also, antidiabetic potential was assessed via α-amylase and α-glucosidase inhibition assays, while cytotoxicity was evaluated using the MTT assay on Caco-2 cells. The results show that ADP supplementation significantly improved dispersibility (up to 72.73% in FCM15D+L). These improvements are attributed to changes in particle size distribution and increased carbohydrate and mineral content, which facilitate powder rehydration and reduce clumping. All FCM variants demonstrated low water activity (0.196–0.226), indicating good potential for shelf stability. The reconstitution properties revealed that FCM powders with ADP had higher bulk and packed densities but lower particle density and porosity than controls. Including ADP reduced interstitial air and increased occluded air within the powders, which may minimize oxidation risks and improve packaging efficiency. ADP incorporation resulted in a significant decrease in lightness (L*) and increases in redness (a*) and yellowness (b*), with greater pigment and phenolic content at higher ADP levels. These changes reflect the natural colorants and browning reactions associated with ADP, leading to a more intense and visually distinct product. Probiotic survivability was higher in ADP-fortified samples, with L. acidophilus and B. bifidum showing resilience in intestinal conditions. The FCM15D+L formulation exhibited potent antidiabetic effects, with IC50 values of 111.43 μg mL−1 for α-amylase and 77.21 μg mL−1 for α-glucosidase activities, though lower than control FCM (8.37 and 10.74 μg mL−1, respectively). Cytotoxicity against Caco-2 cells was most potent in non-ADP samples (IC50: 82.22 μg mL−1 for FCM), suggesting ADP and L. rhamnosus may reduce antiproliferative effects due to proteolytic activity. In conclusion, the study demonstrates that ADP-enriched FCM is a promising functional food with enhanced probiotic viability, antidiabetic potential, and desirable physical properties. This work highlights the potential of camel milk and date synergies in combating some NCDs in vitro, suggesting potential for functional food application. Full article
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19 pages, 738 KiB  
Review
HMGB1 as a Key Modulator in Nasal Inflammatory Disorders: A Narrative Review
by Desiderio Passali, Luisa Maria Bellussi, Mariaconsiglia Santantonio and Giulio Cesare Passali
J. Clin. Med. 2025, 14(15), 5392; https://doi.org/10.3390/jcm14155392 - 31 Jul 2025
Viewed by 230
Abstract
Background: High Mobility Group Box 1 is a mediator in inflammation, acting as a damage-associated molecular pattern molecule in various diseases. This review examines its role in nasal inflammatory disorders, such as chronic rhinosinusitis and allergic rhinitis. Methods: A comprehensive review [...] Read more.
Background: High Mobility Group Box 1 is a mediator in inflammation, acting as a damage-associated molecular pattern molecule in various diseases. This review examines its role in nasal inflammatory disorders, such as chronic rhinosinusitis and allergic rhinitis. Methods: A comprehensive review of recent literature was conducted using a refined PubMed search strategy, focusing on studies published from 2015 onward and targeting HMGB1’s role in nasal inflammatory diseases. Results: HMGB1 emerges as a central factor in amplifying and modulating inflammatory responses through interactions with multiple receptors. It regulates cytokine production, epithelial–mesenchymal transition, and tissue remodeling, particularly in eosinophilic CRS. While discrepancies in the literature highlight its context-dependent activity, therapeutic strategies like glycyrrhetinic acid and PPAR-γ agonists demonstrate potential in modulating its effects. Conclusions: HMGB1 represents a promising diagnostic biomarker and therapeutic target in nasal inflammatory diseases. However, due to its intrinsic nature and multiple localizations, much remains to be understood. It is precisely by reflecting on its role as an “inflammatory crossroads” that we aim to underscore the need for targeted translational research to elucidate the molecular mechanisms and therapeutic applications of HMGB1. Full article
(This article belongs to the Section Otolaryngology)
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14 pages, 1259 KiB  
Review
Engineered Hydrogels for Musculoskeletal Regeneration: Advanced Synthesis Strategies and Therapeutic Efficacy in Preclinical Models
by Gabriela Calin, Mihnea Costescu, Marcela Nour (Cârlig), Tudor Ciuhodaru, Batîr-Marin Denisa, Letitia Doina Duceac, Cozmin Mihai, Melania Florina Munteanu, Svetlana Trifunschi, Alexandru Oancea and Daniela Liliana Damir
Polymers 2025, 17(15), 2094; https://doi.org/10.3390/polym17152094 - 30 Jul 2025
Viewed by 274
Abstract
According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial [...] Read more.
According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial for musculoskeletal tissue regeneration. This is due to their high water content (70–99%), ECM-like structure, injectability, and controllable degradation rates. Recent preclinical studies indicate that they can enhance regeneration by modulating the release of bioactive compounds, growth factors, and stem cells. Composite hydrogels that combine natural and synthetic polymers, like chitosan and collagen, have compressive moduli that are advantageous for tendon–bone healing. Some of these hydrogels can even hold up to 0.8 MPa of tensile strength. In osteoarthritis models, functionalized systems such as microspheres responsive to matrix metalloproteinase-13 have demonstrated disease modulation and targeted drug delivery, while intelligent in situ hydrogels have exhibited a 43% increase in neovascularization and a 50% enhancement in myotube production. Hydrogel-based therapies have been shown to restore contractile force by as much as 80%, increase myofiber density by 65%, and boost ALP activity in bone defects by 2.1 times in volumetric muscle loss (VML) models. Adding TGF-β3 or MSCs to hydrogel systems improved GAG content by about 60%, collagen II expression by 35–50%, and O’Driscoll scores by 35–50% in cartilage regeneration. Full article
(This article belongs to the Section Polymer Applications)
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20 pages, 4117 KiB  
Review
Analytical Strategies for Tocopherols in Vegetable Oils: Advances in Extraction and Detection
by Yingfei Liu, Mengyuan Lv, Yuyang Wang, Jinchao Wei and Di Chen
Pharmaceuticals 2025, 18(8), 1137; https://doi.org/10.3390/ph18081137 - 30 Jul 2025
Viewed by 230
Abstract
Tocopherols, major lipid-soluble components of vitamin E, are essential natural products with significant nutritional and pharmacological value. Their structural diversity and uneven distribution across vegetable oils require accurate analytical strategies for compositional profiling, quality control, and authenticity verification, amid concerns over food fraud [...] Read more.
Tocopherols, major lipid-soluble components of vitamin E, are essential natural products with significant nutritional and pharmacological value. Their structural diversity and uneven distribution across vegetable oils require accurate analytical strategies for compositional profiling, quality control, and authenticity verification, amid concerns over food fraud and regulatory demands. Analytical challenges, such as matrix effects in complex oils and the cost trade-offs of green extraction methods, complicate these processes. This review examines recent advances in tocopherol analysis, focusing on extraction and detection techniques. Green methods like supercritical fluid extraction and deep eutectic solvents offer selectivity and sustainability, though they are costlier than traditional approaches. On the analytical side, hyphenated techniques such as supercritical fluid chromatography-mass spectrometry (SFC-MS) achieve detection limits as low as 0.05 ng/mL, improving sensitivity in complex matrices. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides robust analysis, while spectroscopic and electrochemical sensors offer rapid, cost-effective alternatives for high-throughput screening. The integration of chemometric tools and miniaturized systems supports scalable workflows. Looking ahead, the incorporation of Artificial Intelligence (AI) in oil authentication has the potential to enhance the accuracy and efficiency of future analyses. These innovations could improve our understanding of tocopherol compositions in vegetable oils, supporting more reliable assessments of nutritional value and product authenticity. Full article
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17 pages, 919 KiB  
Article
Timing of Intervals Between Utterances in Typically Developing Infants and Infants Later Diagnosed with Autism Spectrum Disorder
by Zahra Poursoroush, Gordon Ramsay, Ching-Chi Yang, Eugene H. Buder, Edina R. Bene, Pumpki Lei Su, Hyunjoo Yoo, Helen L. Long, Cheryl Klaiman, Moira L. Pileggi, Natalie Brane and D. Kimbrough Oller
Brain Sci. 2025, 15(8), 819; https://doi.org/10.3390/brainsci15080819 - 30 Jul 2025
Viewed by 215
Abstract
Background: Understanding the origin and natural organization of early infant vocalizations is important for predicting communication and language abilities in later years. The very frequent production of speech-like vocalizations (hereafter “protophones”), occurring largely independently of interaction, is part of this developmental process. Objectives: [...] Read more.
Background: Understanding the origin and natural organization of early infant vocalizations is important for predicting communication and language abilities in later years. The very frequent production of speech-like vocalizations (hereafter “protophones”), occurring largely independently of interaction, is part of this developmental process. Objectives: This study aims to investigate the gap durations (time intervals) between protophones, comparing typically developing (TD) infants and infants later diagnosed with autism spectrum disorder (ASD) in a naturalistic setting where endogenous protophones occur frequently. Additionally, we explore potential age-related variations and sex differences in gap durations. Methods: We analyzed ~1500 five min recording segments from longitudinal all-day home recordings of 147 infants (103 TD infants and 44 autistic infants) during their first year of life. The data included over 90,000 infant protophones. Human coding was employed to ensure maximally accurate timing data. This method included the human judgment of gap durations specified based on time-domain and spectrographic displays. Results and Conclusions: Short gap durations occurred between protophones produced by infants, with a mode between 301 and 400 ms, roughly the length of an infant syllable, across all diagnoses, sex, and age groups. However, we found significant differences in the gap duration distributions between ASD and TD groups when infant-directed speech (IDS) was relatively frequent, as well as across age groups and sexes. The Generalized Linear Modeling (GLM) results confirmed these findings and revealed longer gap durations associated with higher IDS, female sex, older age, and TD diagnosis. Age-related differences and sex differences were highly significant for both diagnosis groups. Full article
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17 pages, 3206 KiB  
Article
Inverse Punicines: Isomers of Punicine and Their Application in LiAlO2, Melilite and CaSiO3 Separation
by Maximilian H. Fischer, Ali Zgheib, Iliass El Hraoui, Alena Schnickmann, Thomas Schirmer, Gunnar Jeschke and Andreas Schmidt
Separations 2025, 12(8), 202; https://doi.org/10.3390/separations12080202 - 30 Jul 2025
Viewed by 159
Abstract
The transition to sustainable energy systems demands efficient recycling methods for critical raw materials like lithium. In this study, we present a new class of pH- and light-switchable flotation collectors based on isomeric derivatives of the natural product Punicine, termed inverse Punicines. [...] Read more.
The transition to sustainable energy systems demands efficient recycling methods for critical raw materials like lithium. In this study, we present a new class of pH- and light-switchable flotation collectors based on isomeric derivatives of the natural product Punicine, termed inverse Punicines. These amphoteric molecules were synthesized via a straightforward four-step route and structurally tuned for hydrophobization by alkylation. Their performance as collectors was evaluated in microflotation experiments of lithium aluminate (LiAlO2) and silicate matrix minerals such as melilite and calcium silicate. Characterization techniques including ultraviolet-visible (UV-Vis), nuclear magnetic resonance (NMR) and electron spin resonance (ESR) spectroscopy as well as contact angle, zeta potential (ζ potential) and microflotation experiments revealed strong pH- and structure-dependent interactions with mineral surfaces. Notably, N-alkylated inverse Punicine derivatives showed high flotation yields for LiAlO2 at pH of 11, with a derivative possessing a dodecyl group attached to the nitrogen as collector achieving up to 86% recovery (collector conc. 0.06 mmol/L). Preliminary separation tests showed Li upgrading from 5.27% to 6.95%. Radical formation and light-response behavior were confirmed by ESR and flotation tests under different illumination conditions. These results demonstrate the potential of inverse Punicines as tunable, sustainable flotation reagents for advanced lithium recycling from complex slag systems. Full article
(This article belongs to the Special Issue Application of Green Flotation Technology in Mineral Processing)
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23 pages, 5505 KiB  
Article
Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-like Pain
by José Aviles-Herrera, Guadalupe Esther Ángeles-López, Myrna Déciga-Campos, María Eva González-Trujano, Gabriel Fernando Moreno-Pérez, Ricardo Reyes-Chilpa, Irma Romero, Amalia Alejo-Martínez and Rosa Ventura-Martínez
Molecules 2025, 30(15), 3196; https://doi.org/10.3390/molecules30153196 - 30 Jul 2025
Viewed by 274
Abstract
The objective of this study was to determine the pharmacological interaction of some common NSAIDs in the presence of quercetin (QUER). Indomethacin (IND), ketorolac (KET), or celecoxib (CEL) were assessed alone and in combination with QUER using experimental gout-arthritic pain and the carrageenan-induced [...] Read more.
The objective of this study was to determine the pharmacological interaction of some common NSAIDs in the presence of quercetin (QUER). Indomethacin (IND), ketorolac (KET), or celecoxib (CEL) were assessed alone and in combination with QUER using experimental gout-arthritic pain and the carrageenan-induced edema test in rats to evaluate their antinociceptive and anti-inflammatory effects, respectively. The antinociceptive effect of each NSAID was also analyzed after the repeated administration of QUER for 10 days. Molecular docking analysis on COX-1/COX-2 with each drug was explored to analyze the pharmacological interaction. QUER produced minimal antinociceptive or anti-inflammatory effects on experimental gout-arthritic pain or on the carrageenan-induced edema in rats. Additionally, QUER reduced the antinociceptive effect of NSAIDs, mainly those COX-1 inhibitors (IND and KET), when they were combined. However, QUER did not modify the anti-inflammatory effect of these COX-1 inhibitors and slightly improved the anti-inflammatory effect of the COX-2 inhibitor (CEL). According to the docking analysis, COX-1 and COX-2 are likely implicated in these pharmacological interactions. In conclusion, QUER, a known bioactive natural product, may alter the antinociceptive efficacy of NSAIDs commonly used to relieve gout-like pain and suggests not using them together to prevent a negative therapeutic interaction in this effect. Full article
(This article belongs to the Section Medicinal Chemistry)
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19 pages, 2509 KiB  
Article
Semi-Synthesis, Anti-Leukemia Activity, and Docking Study of Derivatives from 3α,24-Dihydroxylup-20(29)-en-28-Oic Acid
by Mario J. Noh-Burgos, Sergio García-Sánchez, Fernando J. Tun-Rosado, Antonieta Chávez-González, Sergio R. Peraza-Sánchez and Rosa E. Moo-Puc
Molecules 2025, 30(15), 3193; https://doi.org/10.3390/molecules30153193 - 30 Jul 2025
Viewed by 407
Abstract
Current treatments against leukemia present several limitations, prompting the search for new therapeutic agents, particularly those derived from natural products. In this context, structural modifications were performed on the triterpene 3α,24-dihydroxylup-20(29)-en-28-oic acid (T1), isolated from Phoradendron wattii. Among [...] Read more.
Current treatments against leukemia present several limitations, prompting the search for new therapeutic agents, particularly those derived from natural products. In this context, structural modifications were performed on the triterpene 3α,24-dihydroxylup-20(29)-en-28-oic acid (T1), isolated from Phoradendron wattii. Among the five derivatives obtained, 3α,24-dihydroxy-30-oxolup-20(29)-en-28-oic acid (T1c) exhibited the highest activity, with an IC50 value of 12.90 ± 0.1 µM against THP-1 cells. T1c significantly reduced cell viability in both acute lymphoblastic leukemia (CCRF-CEM, REH, JURKAT, and MOLT-4) and acute myeloid leukemia (THP-1) cell lines, inducing apoptosis after 48 h of treatment, while showing minimal cytotoxicity toward normal mononuclear cells (MNCs). In silico molecular docking studies were conducted against three key protein targets: BCL-2 (B-cell lymphoma 2), EGFR (epidermal growth factor receptor, tyrosine kinase domain), and FLT3 (FMS-like tyrosine kinase 3). The lowest binding energies (kcal/mol) observed were as follows: T1–BCL-2: −10.12, EGFR: −12.75, FLT3: −14.05; T1c–BCL-2: −10.23, EGFR: −14.50, FLT3: −14.07; T2–BCL-2: −11.59, EGFR: −15.00, FLT3: −14.03. These findings highlight T1c as a promising candidate in the search for anti-leukemic drugs which deserves further study. Full article
(This article belongs to the Special Issue Synthesis and Derivatization of Heterocyclic Compounds)
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