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19 pages, 4587 KB  
Article
Wet Media Milling Preparation and Process Simulation of Nano-Ursolic Acid
by Guang Li, Wenyu Yuan, Yu Ying and Yang Zhang
Pharmaceutics 2025, 17(10), 1297; https://doi.org/10.3390/pharmaceutics17101297 - 3 Oct 2025
Abstract
Background/Objectives: Pharmaceutical preparation technologies can enhance the bioavailability of poorly water-soluble drugs. Ursolic acid (UA) has been found to possess anti-cancer and hepatoprotective properties, demonstrating its potential as a therapeutic agent; however, its hydrophobicity and low solubility present challenges in the development [...] Read more.
Background/Objectives: Pharmaceutical preparation technologies can enhance the bioavailability of poorly water-soluble drugs. Ursolic acid (UA) has been found to possess anti-cancer and hepatoprotective properties, demonstrating its potential as a therapeutic agent; however, its hydrophobicity and low solubility present challenges in the development of drug formulations. This study investigates the preparation of a nano-UA suspension by wet grinding, researches the influence of process parameters on particle size, and explores the rules of particle breakage and agglomeration by combining model fitting. Methods: Wet grinding experiments were conducted using a laboratory-scale grinding machine. The particle size distributions (PSDs) of UA suspensions under different grinding conditions were measured using a laser particle size analyzer. A single-factor experimental design was employed to optimize operational conditions. Model parameters for a population balance model considering both breakage and agglomeration were determined by an evolutionary algorithm optimization method. By measuring the degree to which UA inhibits the colorimetric reaction between salicylic acid and hydroxyl radicals, its antioxidant capacity in scavenging hydroxyl radicals was indirectly evaluated. Results: Wet grinding process conditions for nano-UA particles were established, yielding a UA suspension with a D50 particle size of 122 nm. The scavenging rate of the final grinding product was improved to three times higher than that of the UA raw material (D50 = 14.2 μm). Conclusions: Preparing nano-UA suspensions via wet grinding technology can significantly enhance their antioxidant properties. Model regression analysis of PSD data reveals that increasing the grinding mill’s stirring speed leads to more uniform particle size distribution, indicating that grinding speed (power) is a critical factor in producing nanosuspensions. Full article
(This article belongs to the Special Issue Advanced Research on Amorphous Drugs)
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12 pages, 645 KB  
Article
Solubility Modeling of Sabah Green Robusta Coffee (Coffea canephora) Bean Oil Extracted Using Supercritical Carbon Dioxide
by Sarah Aisyah Khurun Hizar, Hasmadi Mamat, Wolyna Pindi, Norliza Julmohammad, Siti Faridah Mohd Amin, Mohd Azrie Awang, Jumardi Roslan, Muhammad Abbas Ahmad Zaini, Nicky Rahmana Putra, Abdul Aziz Jaziri, Norzalizan Ishak and Ahmad Hazim Abdul Aziz
Sci 2025, 7(4), 139; https://doi.org/10.3390/sci7040139 - 2 Oct 2025
Abstract
This study investigates the solubility correlation of oil extracted from Sabah green Robusta coffee (Coffea canephora) beans through supercritical carbon dioxide (SC-CO2) extraction. Sabah, recognized as the largest coffee-producing region in Malaysia, serves as a significant source of Robusta [...] Read more.
This study investigates the solubility correlation of oil extracted from Sabah green Robusta coffee (Coffea canephora) beans through supercritical carbon dioxide (SC-CO2) extraction. Sabah, recognized as the largest coffee-producing region in Malaysia, serves as a significant source of Robusta beans for this research. The solubility of coffee bean oil was evaluated under varying pressures (10–30 MPa) and temperatures (40–80 °C). The maximum solubility, 2.681 mg/g CO2, was recorded at 30 MPa and 40 °C, whereas the lowest solubility, approximately 0.440 mg/g CO2, occurred at 20 MPa and 80 °C. A clear inverse relationship between solubility and temperature was observed, with solubility decreasing as temperature increased to 80 °C. Conversely, elevated pressure, particularly at 30 MPa, enhanced solubility due to the increased density and solvent power of SC-CO2. Experimental data exhibited strong agreement with Chrastil’s equation, yielding a relatively low percentage error of 3.37%, compared with 14.57% for the del Valle-Aguilera model. These findings demonstrate the reliability of Chrastil’s model in predicting the solubility of Sabah green coffee bean oil in SC-CO2. Overall, the research highlights the potential of SC-CO2 extraction as a sustainable, solvent-free approach for obtaining high-quality coffee oil extracts, with promising applications in the food industry and possible extension to the recovery of other bioactive compounds in food processing. Full article
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14 pages, 7505 KB  
Article
Parent-of-Origin Effect Predominantly Drives Seedling Vigor Heterosis in Triploid Loquat
by Chi Zhang, Ting Yuan, Jun Liang, Qigao Guo, Linghan Jia, Jiangbo Dang, Di Wu and Guolu Liang
Horticulturae 2025, 11(10), 1175; https://doi.org/10.3390/horticulturae11101175 - 2 Oct 2025
Abstract
Triploid breeding is a promising approach for developing seedless varieties, but the long juvenile phase of perennial fruit trees necessitates efficient early selection. In loquat (Eriobotrya japonica), a fruit crop with high demand for seedlessness, the relative contributions of hybridity, ploidy [...] Read more.
Triploid breeding is a promising approach for developing seedless varieties, but the long juvenile phase of perennial fruit trees necessitates efficient early selection. In loquat (Eriobotrya japonica), a fruit crop with high demand for seedlessness, the relative contributions of hybridity, ploidy level, and parent-of-origin effects (POEs) to triploid seedling vigor remain elusive. To dissect these factors, we established a comprehensive experimental system comprising reciprocal diploid (2x), triploid (3x), and tetraploid (4x) hybrids from two genetically distinct cultivars. The ploidy, hybridity and genetic architecture of hybrid and parental groups were verified using flow cytometry, chromosome counting, newly developed InDel markers and genome-wide SNP analysis. Phenotypic evaluation of eight vigor-related traits revealed that plant height and soluble starch content were the most robust indicators of triploid heterosis in loquat. Notably, paternal-excess triploids [3x(p)] consistently outperformed all other groups. Quantitative analysis revealed POE as the main positive driver of triploid heterosis (+10.37% for plant height), far exceeding the negative impacts of hybridity (−12.75%) and ploidy level (−20.87%). These findings demonstrate that POE predominantly drives seedling vigor heterosis in triploid loquat. We propose a practical breeding strategy that combines prioritizing paternal-excess crosses with novel InDel markers for rapid verification of superior seedless progeny. Full article
(This article belongs to the Section Genetics, Genomics, Breeding, and Biotechnology (G2B2))
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15 pages, 1631 KB  
Article
Towards Sustainable Biogas Production: Valorizing Dairy Waste Through Green Thermo-Oxidative Pretreatment
by Bani Kheiredine, Kerroum Derbal, Maissa Talhi, Randa Touil, Meriem Zamouche, Sabrina Lekmine, Mohammad Shamsul Ola, Jie Zhang, Abdeltif Amrane and Hichem Tahraoui
Water 2025, 17(19), 2844; https://doi.org/10.3390/w17192844 - 29 Sep 2025
Abstract
This study was conducted to investigate the effect of hydrogen peroxide (H2O2) pretreatment on the anaerobic digestion performance of dairy wastewater. Initial physicochemical characterization revealed that the substrate is highly enriched in volatile solids (approximately 90.67%), indicating its strong [...] Read more.
This study was conducted to investigate the effect of hydrogen peroxide (H2O2) pretreatment on the anaerobic digestion performance of dairy wastewater. Initial physicochemical characterization revealed that the substrate is highly enriched in volatile solids (approximately 90.67%), indicating its strong potential for anaerobic biodegradation. Given this favorable composition, biochemical methane potential (BMP) assays were performed under mesophilic conditions (37 °C) to quantify biogas and methane generation from the untreated and pretreated dairy effluent. To enhance substrate biodegradability and increase methane yield, an oxidative pretreatment using various doses of H2O2 was applied. This pretreatment aimed to disrupt the complex organic matter and promote the solubilization of chemical oxygen demand (COD), especially in its soluble form (sCOD), which is more readily assimilated by methanogenic microorganisms. The experimental results demonstrated a significant improvement in biogas production efficiency. While the untreated sample yielded approximately 100 mL CH4/g VS, the pretreated substrate achieved a maximum of 168 mL CH4/g VS, marking a substantial enhancement. Gas composition analysis further revealed that methane accounted for nearly 45% of the total biogas produced under optimal conditions. The dosage of 0.2 g H2O2 per g of volatile solids (VS) resulted in the highest improvement in methane production after thermal treatment C1, followed by 1.35 g H2O2/g VS, and then 0.5 g H2O2/g VS. Furthermore, the kinetics of methane production were assessed by fitting the experimental data to the modified Gompertz model. This model enabled the determination of key parameters, such as the maximum specific methane production rate and the duration of the lag phase. The high coefficient of determination (R2) values obtained confirmed the excellent agreement between the experimental data and the model predictions, highlighting the robustness and reliability of the modified Gompertz model in describing the anaerobic digestion process of dairy waste subjected to oxidative pretreatment. Full article
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21 pages, 7579 KB  
Article
Mechanisms of Morphological Development and Physiological Responses Regulated by Light Spectrum in Changchuan No. 3 Pepper Seedlings
by Wanli Zhu, Zhi Huang, Shiting Zhao, Zhi Chen, Bo Xu, Qiang Huang, Yuna Wang, Yu Wu, Yuanzhen Guo, Hailing Chen and Lanping Shi
Horticulturae 2025, 11(10), 1161; https://doi.org/10.3390/horticulturae11101161 - 29 Sep 2025
Abstract
This study aimed to evaluate the effects of specific LED light spectra on the growth and physiology of Changchuan No. 3 Capsicum annuum L. seedlings. The experimental design involved exposing pepper seedlings to six different spectral light combinations for 7, 14, and 21 [...] Read more.
This study aimed to evaluate the effects of specific LED light spectra on the growth and physiology of Changchuan No. 3 Capsicum annuum L. seedlings. The experimental design involved exposing pepper seedlings to six different spectral light combinations for 7, 14, and 21 days, with the treatments consisting of 2R1B1Y (red/blue/yellow = 2:1:1), 2R1B1FR (red/blue/far-red = 2:1:1), 2R1B1P (red/blue/purple = 2:1:1), 4R2B1G (red/blue/green = 4:2:1), 2R1B1G (red/blue/green = 2:1:1), and 2R1B (red/blue = 2:1). The results demonstrated distinct spectral regulation of seedling development: compared to the white light (CK), the 2R1B1FR (far-red light supplementation) treatment progressively stimulated stem elongation, increasing plant height and stem diameter by 81.6% and 25.9%, respectively, at day 21, but resulted in a more slender stem architecture. The 2R1B1G (balanced green light) treatment consistently promoted balanced growth, culminating in the highest seedling vigor index at the final stage. The 2R1B1P (purple light supplementation) treatment exhibited a strong promotive effect on root development, which became most pronounced at day 21 (126% increase in root dry weight), while concurrently enhancing soluble sugar content and reducing oxidative stress. Conversely, the 2R1B1Y (yellow light supplementation) treatment increased MDA content by 70% and led to a reduction in chlorophyll accumulation, while 2R1B (basic red–blue) resulted in lower biomass accumulation compared to the superior spectral treatments. The 4R2B1G (low green ratio) treatment showed context-dependent outcomes. This study elucidates how targeted spectral compositions, particularly involving far-red and green light, can optimize pepper seedling quality by modulating photomorphogenesis, carbon allocation, and stress physiology. The findings provide a mechanistic basis for designing efficient LED lighting protocols in controlled-environment agriculture to enhance pepper nursery production. Full article
(This article belongs to the Special Issue Genomics and Genetic Diversity in Vegetable Crops)
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22 pages, 5125 KB  
Review
Ivermectin as an Alternative Anticancer Agent: A Review of Its Chemical Properties and Therapeutic Potential
by Kimberly Naula Robalino, Oscar Vivanco-Galván, Juan Carlos Romero-Benavides and Yuliana Jiménez-Gaona
Pharmaceuticals 2025, 18(10), 1459; https://doi.org/10.3390/ph18101459 - 28 Sep 2025
Abstract
Background: Ivermectin has recently garnered significant scientific attention for its potential anticancer properties. Objective: This research aims a comprehensive literature review to evaluate IVM’s chemical characteristics and assess its applicability as an alternative therapeutic strategy in oncology. Methods: The methodology involved a systematic [...] Read more.
Background: Ivermectin has recently garnered significant scientific attention for its potential anticancer properties. Objective: This research aims a comprehensive literature review to evaluate IVM’s chemical characteristics and assess its applicability as an alternative therapeutic strategy in oncology. Methods: The methodology involved a systematic search and critical appraisal of data from peer-reviewed scientific databases, focusing on structural analyses, such as nuclear magnetic resonance (NMR), crystallography, and in silico modeling, as well as preclinical experimental studies. Results: The review highlights IVM’s distinct physicochemical profile, including high lipophilicity, poor aqueous solubility, and moderate acid stability, which collectively affect its bioavailability and pharmacokinetic behavior. Mechanistically, IVM has been shown to modulate multiple oncogenic signaling pathways, including Wnt/β-catenin, PI3K/Akt/mTOR, and STAT3. These interactions contribute to the induction of apoptosis, inhibition of tumor cell proliferation, and modulation of the tumor microenvironment across a range of malignancies. Despite encouraging preclinical evidence, clinical validation remains limited. Conclusions: Further investigation is needed to optimize IVM’s formulation for enhanced solubility and targeted delivery, as well as to design robust clinical trials assessing its safety and efficacy in oncology settings. This review provides a foundational framework for future interdisciplinary research on drug repurposing and highlights the potential of IVM as a cost-effective and accessible adjunct or alternative to modern cancer therapy. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment: 2nd Edition)
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37 pages, 1945 KB  
Review
Shikonin as a Dietary Phytochemical with Multi-Target Anti-Cancer Activities: From Molecular Mechanisms to Translational Applications
by Chun-Yik Lew, Yi-Teng Tang, Amanda Yee-Jing Lee, Zhi-Jian Chin, Wan-Ling Chang, Ching-Hsein Chen and Soi-Moi Chye
Nutrients 2025, 17(19), 3085; https://doi.org/10.3390/nu17193085 - 28 Sep 2025
Abstract
Shikonin, a dietary naphthoquinone phytochemical from the roots of Lithospermum erythrorhizon, has gained attention for its anticancer potential. Preclinical studies show that shikonin regulates multiple programmed cell death pathways, including apoptosis, necroptosis, ferroptosis, and pyroptosis, through mechanisms involving reactive oxygen species (ROS) [...] Read more.
Shikonin, a dietary naphthoquinone phytochemical from the roots of Lithospermum erythrorhizon, has gained attention for its anticancer potential. Preclinical studies show that shikonin regulates multiple programmed cell death pathways, including apoptosis, necroptosis, ferroptosis, and pyroptosis, through mechanisms involving reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and kinase-mediated signalling. Beyond cytotoxicity, shikonin suppresses metastasis by blocking epithelial–mesenchymal transition (EMT) and downregulating matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). It also disrupts tumour metabolism by targeting pyruvate kinase isoform M2 (PKM2) and modulating the Warburg effect. Evidence further indicates that shikonin can enhance the efficacy of chemotherapy, targeted therapy, immunotherapy, and radiotherapy, thereby contributing to the reversal of therapeutic resistance. To address limitations related to solubility and bioavailability, novel formulations such as nanoparticles, liposomes, and derivatives like β,β-dimethylacrylshikonin have been developed, showing improved pharmacological profiles and reduced toxicity in experimental models. Overall, the current literature identifies shikonin as a promising dietary phytochemical with diverse anticancer activities, therapeutic synergy, and formulation advances, while highlighting the need for clinical studies to establish its translational potential. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals: 2nd Edition)
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27 pages, 2965 KB  
Article
Exogenous Spermidine Induces Cadmium Stress Tolerance in Cucumber Seedlings by Promoting Plant Growth and Defense System
by Guangchao Yu, Ming Wei, Zhipeng Wang, Lian Jia and Yue Qu
Toxics 2025, 13(10), 822; https://doi.org/10.3390/toxics13100822 - 26 Sep 2025
Abstract
This study aims to investigate the role of exogenous spermidine (Spd) in mitigating the adverse effects of cadmium (Cd) stress on the growth and development of cucumber (Cucumis sativus). The cucumber cultivar “Xintaimici” was used as the experimental material, and a [...] Read more.
This study aims to investigate the role of exogenous spermidine (Spd) in mitigating the adverse effects of cadmium (Cd) stress on the growth and development of cucumber (Cucumis sativus). The cucumber cultivar “Xintaimici” was used as the experimental material, and a hydroponic experiment was carried out. Based on a baseline Cd concentration of 10 mg·L−1, Spd was supplemented at concentrations of 0.05, 0.1, 0.2, 0.4, and 0.5 mM, resulting in seven treatment groups: control group (CK), S0 group (Cd-only treatment, 10 mg·L−1 Cd + 0 mM Spd), S1+ Cd group (10 mg·L−1 Cd + 0.05 mM Spd), S2+ Cd group (10 mg·L−1 Cd + 0.1 mM Spd), S3+ Cd group (10 mg·L−1 Cd + 0.2 mM Spd), S4+ Cd group (10 mg·L−1 Cd + 0.4 mM Spd), and S5+ Cd group (10 mg·L−1 Cd + 0.5 mM Spd). This study analyzed the regulatory effects of Spd on the growth and development, antioxidant capacity and cadmium accumulation characteristics of cucumber seeds and seedlings. It was found that cadmium stress significantly inhibited their growth process and led to a decline in multiple physiological indicators. Under a Cd concentration of 10 mg·L−1, the application of 0.2 mM Spd significantly improved these parameters. During the seedling stage, the application of 0.2 mM Spd under Cd stress significantly enhanced the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), as well as the content of soluble proteins, while significantly reducing malondialdehyde (MDA) levels. Cd content analysis revealed that 0.2 mM Spd promoted Cd accumulation in roots while suppressing its translocation to young leaves, thereby reducing Cd accumulation in aboveground tissues. Gene expression analysis demonstrated that this treatment significantly upregulated the expression levels of the phytochelatin synthase gene (CsPCS1) and the gene associated with reduced glutathione synthesis (CsGSHS). In conclusion, the exogenous application of 0.2 mM Spd effectively alleviates oxidative damage and osmotic stress induced by Cd stress in cucumber, promotes plant growth, and significantly enhances Cd tolerance. Full article
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19 pages, 864 KB  
Review
The Role of Vitamin C in Selected Autoimmune and Immune-Mediated Diseases: Exploring Potential Therapeutic Benefits
by Martyna Mochol, Lukasz Jablonowski, Andrzej Pawlik, Joanna Rasławska-Socha, Agnieszka Chamarczuk, Mariusz Lipski and Małgorzata Mazurek-Mochol
Int. J. Mol. Sci. 2025, 26(19), 9375; https://doi.org/10.3390/ijms26199375 - 25 Sep 2025
Abstract
Autoimmune diseases are characterized by immune response dysregulation against self-components, leading to chronic inflammation and tissue damage. Vitamin C (VitC), a water-soluble vitamin with established functions in antioxidant defence and collagen synthesis, has also been of interest based on its potential immunomodulatory effects. [...] Read more.
Autoimmune diseases are characterized by immune response dysregulation against self-components, leading to chronic inflammation and tissue damage. Vitamin C (VitC), a water-soluble vitamin with established functions in antioxidant defence and collagen synthesis, has also been of interest based on its potential immunomodulatory effects. This review discusses the role of VitC in the course and progression of (A) autoimmune diseases (multiple sclerosis, rheumatoid arthritis, Sjögren’s disease, type 1 diabetes, Hashimoto’s thyroiditis, pernicious anaemia, antiphospholipid syndrome), (B) other immune-mediated diseases (Crohn’s disease, periodontitis), and (C) Alzheimer’s disease, a neurodegenerative disorder with autoimmune features. Results from clinical, observational, and experimental trials show that VitC deficiency is common in many of these diseases and may contribute to increased oxidative stress and immune disequilibrium. Supplementation has been associated with improved antioxidant levels, control of inflammatory mediators, and, in some cases, clinical outcomes like disease activity decrease or symptom load. Although findings vary across conditions and few large, randomized trials are available, the overall evidence indicates that maintaining good VitC status can be useful in maintaining immune homeostasis and reducing inflammation. VitC should be viewed as an adjunct to be employed safely, perhaps and ideally within larger treatment regimens, but not in place of effective therapies. Further research, including large-scale clinical trials, will be required to determine more clearly optimal dosing, timing of treatment, and patient population most likely to benefit. By integration of current knowledge, this review recognizes both promise in VitC for treatment of autoimmune/immune-mediated disease and promise in its potential use within future treatment regimens. Full article
(This article belongs to the Special Issue Lipids and Vitamins in Health and Disease)
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21 pages, 2296 KB  
Article
Integrated Transcriptomic and Metabolomic Analyses of Seed-Filling Disorders in Soybeans Under Different Ecological Conditions
by Junxia Huang, Wei Zheng, Zicong Liang, Zhenghao Zhang, Jiayi Li, Huijun Zhang, Haiying Wang, Xue Ao, Xingdong Yao and Futi Xie
Agronomy 2025, 15(10), 2266; https://doi.org/10.3390/agronomy15102266 - 24 Sep 2025
Viewed by 17
Abstract
Disorders in soybean seed-filling can lead to wrinkled seeds, affecting yield and quality. Previous studies have demonstrated that some soybean cultivars from Jiamusi, Heilongjiang Province (cold-temperate continental monsoon, ~3.5 °C mean annual temperature, ~530 mm precipitation) exhibit seed-filling disorders when cultivated in Shenyang, [...] Read more.
Disorders in soybean seed-filling can lead to wrinkled seeds, affecting yield and quality. Previous studies have demonstrated that some soybean cultivars from Jiamusi, Heilongjiang Province (cold-temperate continental monsoon, ~3.5 °C mean annual temperature, ~530 mm precipitation) exhibit seed-filling disorders when cultivated in Shenyang, Liaoning Province (mid-temperate semi-humid continental monsoon, ~8.3 °C, ~610 mm). However, the causes and regulatory mechanisms remain unclear. In this study, Henong 76 (a soybean cultivar with seeds less prone to wrinkling) and Heihe 43 (a soybean cultivar with seeds prone to wrinkling) were used as experimental materials. They were sown simultaneously in Jiamusi and Shenyang, respectively, to explore the causes of seed-filling disorders in Heihe 43. The results indicated that there were significant differences in the contents of soluble sugars and starch, as well as in the activities of sucrose synthase and invertase, between the seeds of Henong 76 and Heihe 43 grown in Shenyang. However, no significant differences were found between them in Jiamusi. Transcriptomic and metabolomic analyses suggested that genes related to controlling starch hydrolysis (isoamylase, α-amylase, and glycogen phosphorylase) and sucrose synthesis and decomposition (sucrose synthase, invertase, glucose-6-phosphate isomerase, and phosphoglucomutase) in Heihe 43 were upregulated in Shenyang. In contrast, genes regulating plant hormone signal transduction (auxin, gibberellin, abscisic acid, and cytokinin) were generally downregulated. These changes led to differences in metabolites, resulting in the occurrence of seed-filling disorders. Furthermore, we analyzed the climatic conditions of the two cultivars during the soybean seed-filling period. The results indicated that high temperature might be the primary meteorological factor contributing to the occurrence of seed-filling disorders. All results indicated that the insufficient accumulation of sugars in seeds due to exposure to high temperatures during the seed-filling period is the primary cause of the prone-to-wrinkling phenomenon of the Heihe 43 cultivar under the ecological conditions of Shenyang. Full article
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33 pages, 6726 KB  
Review
Recent Techniques to Improve Amorphous Dispersion Performance with Quality Design, Physicochemical Monitoring, Molecular Simulation, and Machine Learning
by Hari Prasad Bhatta, Hyo-Kyung Han, Ravi Maharjan and Seong Hoon Jeong
Pharmaceutics 2025, 17(10), 1249; https://doi.org/10.3390/pharmaceutics17101249 - 24 Sep 2025
Viewed by 183
Abstract
Amorphous solid dispersions (ASDs) represent a promising formulation strategy for improving the solubility and bioavailability of poorly water-soluble drugs, a major challenge in pharmaceutical development. This review provides a comprehensive analysis of the physicochemical principles underlying ASD stability, with a focus on drug–polymer [...] Read more.
Amorphous solid dispersions (ASDs) represent a promising formulation strategy for improving the solubility and bioavailability of poorly water-soluble drugs, a major challenge in pharmaceutical development. This review provides a comprehensive analysis of the physicochemical principles underlying ASD stability, with a focus on drug–polymer miscibility, molecular mobility, and thermodynamic properties. The main manufacturing techniques including hot-melt extrusion, spray drying, and KinetiSol® dispersing are discussed for their impact on formulation homogeneity and scalability. Recent advances in excipient selection, molecular modeling, and in silico predictive approaches have transformed ASD design, reducing dependence on traditional trial-and-error methods. Furthermore, machine learning and artificial intelligence (AI)-based computational platforms are reshaping formulation strategies by enabling accurate predictions of drug–polymer interactions and physical stability. Advanced characterization methods such as solid-state NMR, IR, and dielectric spectroscopy provide valuable insights into phase separation and recrystallization. Despite these technological innovations, ensuring long-term stability and maintaining supersaturation remain significant challenges for ASDs. Integrated formulation design frameworks, including PBPK modeling and accelerated stability testing, offer potential solutions to address these issues. Future research should emphasize interdisciplinary collaboration, leveraging computational advancements together with experimental validation to refine formulation strategies and accelerate clinical translation. The scientists can unlock the full therapeutic potential with emerging technologies and a data-driven approach. Full article
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28 pages, 10704 KB  
Article
NanoDeNovo: De Novo Design of Anti-Poliovirus I Sabin Strain Nanobodies by Semi-Automated Computational Pipeline
by Danil D. Kotelnikov, Katerina S. Tatarinova and Dmitry D. Zhdanov
Int. J. Mol. Sci. 2025, 26(19), 9262; https://doi.org/10.3390/ijms26199262 - 23 Sep 2025
Viewed by 137
Abstract
Despite global vaccination efforts, poliomyelitis continues to cause paralytic cases, highlighting the need for alternative therapeutic approaches. Nanobodies offer significant advantages over conventional antibodies due to their small size, stability, and low immunogenicity, yet few have been developed specifically against poliovirus. This study [...] Read more.
Despite global vaccination efforts, poliomyelitis continues to cause paralytic cases, highlighting the need for alternative therapeutic approaches. Nanobodies offer significant advantages over conventional antibodies due to their small size, stability, and low immunogenicity, yet few have been developed specifically against poliovirus. This study presents a fully computational pipeline for de novo design of nanobodies targeting Virus Protein 3 (VP3) of the Poliovirus I Sabin strain. Our integrated approach employed Ig-VAE for scaffold generation, ProteinMPNN and RFantibody for sequence design, tFold-Ab/Ag for structure prediction, multi-platform molecular docking (Rfantibody, Rosetta3, ClusPro2, ReplicaDock 2.0), molecular dynamics simulations, and humanization tools. The pipeline identified three humanized nanobodies (scFv-0389-304-6H, scFv-0389-459-5H, and scFv-0743-166-7/H) that demonstrated strong binding to VP3 with binding free energies of −37.66 ± 10.35, −40.11 ± 20.01, and −48.62 ± 11.21 kcal/mol, respectively. All designs exhibited favorable physicochemical properties and high solubility. Notably, nanobodies humanized prior to CDR-loop design (scFv-0743-166-7/H) showed superior stability, binding affinity, and structural similarity to experimentally validated nanobodies. This work demonstrates the feasibility of a fully computational approach for designing promising nanobodies against viral targets, providing an alternative to traditional methods with potential applications in drug design. Full article
(This article belongs to the Special Issue Advances in Biomathematics, Computational Biology, and Bioengineering)
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25 pages, 5375 KB  
Article
The Impact of Varieties and Growth Stages on the Production Performance and Nutritional Quality of Forage Triticale in the Qaidam Basin
by Fengjuan Xue, Chengti Xu, Yuanyuan Zhao, Xiaojian Pu, Jie Wang, Xiaoli Wei and Wei Wang
Plants 2025, 14(19), 2942; https://doi.org/10.3390/plants14192942 - 23 Sep 2025
Viewed by 161
Abstract
Insufficient forage is a significant factor limiting the development of animal husbandry in high-altitude pastoral areas. This study aims to identify suitable high-quality forage Triticale (x Triticosecale Wittmack) varieties for cultivation in the Qaidam Basin and determine their optimal harvest period. Seven triticale [...] Read more.
Insufficient forage is a significant factor limiting the development of animal husbandry in high-altitude pastoral areas. This study aims to identify suitable high-quality forage Triticale (x Triticosecale Wittmack) varieties for cultivation in the Qaidam Basin and determine their optimal harvest period. Seven triticale varieties were selected as experimental materials, and their production performance and nutritional quality were comprehensively analyzed at four different growth stages [booting stage (BTS), heading stage (HDS), flowering stage (FLS), and milk stage (MKS)] in 2024 and 2025, utilizing Pearson correlation analysis, PCA, and TOPSIS methods. The results indicated that as the reproductive period progressed, plant height, dry matter yield, and dry matter content exhibited a continuous increase. In contrast, indicators such as stem diameter, number of green leaves, and fresh biomass yield initially increased before subsequently declining. The MKS soluble sugar content (SS) and relative feed value (RFV) were the highest, crude protein (CP) and crude ash content (CA) decreased, the neutral detergent fiber content (NDF) and the acid detergent fiber (ADF) content reached their peak in the HDS. The relative forage quality (RFQ) reached its peak during the flowering period. Comprehensive analysis showed that the top five rankings are QSM-8 > JSM-3 > QSM-1 > JSM-2 > QSM-7. In the Qaidam Basin, the optimal harvest period from the FLS to the MKS ensures both high yield and good nutritional quality, making it suitable for promotion in the Qaidam Basin region and similar ecological zones. Full article
(This article belongs to the Section Crop Physiology and Crop Production)
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12 pages, 1334 KB  
Article
Improving Bonding Durability in Dental Restorations: The Impact of Bioactive and Reinforcement Particles on Universal Adhesives
by William Cunha Brandt, Isaías Donizeti Silva, Andreia Carneiro Matos, Flávia Gonçalves and Leticia Boaro
Materials 2025, 18(19), 4433; https://doi.org/10.3390/ma18194433 - 23 Sep 2025
Viewed by 121
Abstract
Objective: This study aimed to evaluate the effect of incorporating bioactive particles (montmorillonite loaded with chlorhexidine, MMT/CHX) and different concentrations of silica nanoparticles (0%, 3%, 5%, 7%, 10%, and 15 wt%) into a universal dental adhesive on its degree of conversion, bond strength, [...] Read more.
Objective: This study aimed to evaluate the effect of incorporating bioactive particles (montmorillonite loaded with chlorhexidine, MMT/CHX) and different concentrations of silica nanoparticles (0%, 3%, 5%, 7%, 10%, and 15 wt%) into a universal dental adhesive on its degree of conversion, bond strength, water sorption, solubility, and antimicrobial activity. Materials and Methods: A universal adhesive was modified with 1 wt% MMT/CHX and varying amounts of silica nanoparticles. Degree of conversion was analyzed by Fourier transform infrared spectroscopy (FTIR), and microtensile bond strength was evaluated at 24 h, 6 months, and 12 months after water storage. Water sorption and solubility were measured according to ISO 4049, and antibacterial activity was tested against Streptococcus mutans using the agar diffusion method. Results: All experimental adhesives containing ≥7% silica showed significantly reduced water sorption and solubility. The presence of MMT/CHX imparted consistent antimicrobial activity across all experimental groups. Degree of conversion remained stable across all groups and storage periods. Notably, after 12 months, only the experimental groups maintained or improved bond strength, while the control group showed a significant reduction. Failure mode analysis indicated increased mechanical integrity with higher filler content. Conclusions: Incorporating 1 wt% MMT/CHX and ≥7 wt% silica into a universal adhesive improved long-term bond strength, reduced degradation, and introduced antibacterial properties without compromising polymer conversion. These findings support the potential of developing durable, bioactive adhesive systems for restorative dentistry. Clinical Significance: The incorporation of bioactive and reinforcing nanoparticles into universal adhesives enhances bond durability and introduces antibacterial properties without compromising polymerization. This innovation may lead to longer-lasting restorations and reduced risk of secondary caries in clinical practice. Full article
(This article belongs to the Special Issue Recent Research in Restorative Dental Materials)
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Article
CO2 Solubility in Aqueous Solutions of Amine–Ionic Liquid Blends: Experimental Data for Mixtures with AMP and MAPA and Modeling with the Modified Kent–Eisenberg Model
by Giannis Kontos and Ioannis Tsivintzelis
Molecules 2025, 30(18), 3832; https://doi.org/10.3390/molecules30183832 - 21 Sep 2025
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Abstract
Carbon dioxide (CO2) capture using alkanolamines remains the most mature technology, yet faces challenges including solvent loss, high regeneration energy and equipment corrosion. Ionic liquids (ILs) are proposed as alternatives, but their high viscosity and production costs hinder industrial use. Thus, [...] Read more.
Carbon dioxide (CO2) capture using alkanolamines remains the most mature technology, yet faces challenges including solvent loss, high regeneration energy and equipment corrosion. Ionic liquids (ILs) are proposed as alternatives, but their high viscosity and production costs hinder industrial use. Thus, blending ILs with amines offers a promising approach. This work presents new experimental data for aqueous blends of 1-butyl-3-methylimidazolium hydrogen sulfate, Bmim+HSO4, with 2-amino-2-methyl-1-propanol (AMP) and 3-(methylamino)propylamine (MAPA) and for choline glycine, Ch+Gly, with AMP, modeled using the modified Kent–Eisenberg approach. It was shown that substituting a portion of the amine with Bmim+HSO4 reduces CO2 uptake per mole of amine due to the lower solution’s basicity, despite the added sites for physical absorption. In contrast, the replacement of an amine portion with Ch+Gly enhances both physical and chemical interactions, leading to increased CO2 solubility per mole of amine. Finally, replacing a small portion of water with [Ch+][Gly] does not significantly alter the bulk CO2 solubility (moles of CO2 per kg of solvent) but lowers the solvent’s vapor pressure. Given the non-toxic nature of [Ch+][Gly], the resulting solvent poses no added environmental risk. Model predictions agree well with experimental data (deviations of 2.0–11.6%) and indicate low unreacted amine content at CO2 partial pressures of 1–10 kPa for carbamate-forming amines, i.e., Gly, and MAPA. Consequently, at higher CO2 partial pressures, the solubility increases due to carbamate hydrolysis and molecular CO2 dissolution. Full article
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