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Search Results (325)

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14 pages, 3359 KB  
Article
Effects of Boron Addition on Microstructure and Mechanical Properties of B4C/Al Composites Fabricated by Pressureless Infiltration
by Yao Liu, Jianle Xie, Hao Peng, Chunli Liu, Donglin Ma and Yongxiang Leng
Metals 2025, 15(8), 919; https://doi.org/10.3390/met15080919 - 19 Aug 2025
Viewed by 343
Abstract
Boron (B) is widely used as a neutron-absorbing nuclide and has significant applications in the nuclear industry. B4C/Al composites combine the high hardness of B4C with the ductility of Al, making them commonly used neutron-absorbing materials. Under current preparation [...] Read more.
Boron (B) is widely used as a neutron-absorbing nuclide and has significant applications in the nuclear industry. B4C/Al composites combine the high hardness of B4C with the ductility of Al, making them commonly used neutron-absorbing materials. Under current preparation methods, the poor wettability and low reactivity of B4C with molten Al limit its effective incorporation into the matrix, and the addition of B4C in B4C/Al composites has reached its threshold limit, making it difficult to achieve breakthrough improvements in neutron absorption performance. However, incorporating additional B elements into the B4C/Al composite can break this limit, effectively enhancing the material’s neutron absorption performance. Nevertheless, research on the impact of this addition on the mechanical properties of the composite remains unclear. The requirements for B4C/Al composites as spent fuel storage and transportation devices include high mechanical strength and certain machinability. This study fabricated B4C/Al composites with varying B contents (5 wt.%, 10 wt.%, and 15 wt.%), and the influence of B addition on the microstructure and mechanical properties of B4C/Al composites was investigated. The results demonstrate that the composites exhibit a density of approximately 99% with well-established interfacial bonds. Increasing B content leads to a higher quantity of interfacial reaction products Al3BC and AlB2, enhancing the Vickers hardness to 370.93 HV. The bending strength and fracture toughness of composites with 5 wt.% and 15 wt.% B addition decreased, whereas those with 10 wt.% B exhibited excellent resistance to crack growth and high-temperature plastic deformation due to a high content of ductile phase. Full article
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16 pages, 6137 KB  
Article
Synergistic Optimization of High-Temperature Mechanical Properties and Thermal Conductivity in B4C/Al Composites Through Nano-Al2O3 Phase Transformation and Process Engineering
by Chunfa Huang, Lingmin Li and Qiulin Li
Metals 2025, 15(8), 874; https://doi.org/10.3390/met15080874 - 4 Aug 2025
Viewed by 347
Abstract
To address the critical challenge of synergistically enhancing both high-temperature mechanical properties and thermal conductivity in neutron-absorbing materials for dry storage of spent nuclear fuel, this study proposes an innovative strategy. This approach involves the controlled distribution, size, and crystalline states of nano-Al [...] Read more.
To address the critical challenge of synergistically enhancing both high-temperature mechanical properties and thermal conductivity in neutron-absorbing materials for dry storage of spent nuclear fuel, this study proposes an innovative strategy. This approach involves the controlled distribution, size, and crystalline states of nano-Al2O3 within an aluminum matrix. By combining plastic deformation and heat treatment, we aim to achieve a structurally integrated functional design. A systematic investigation was conducted on the microstructural evolution of Al2O3/10 wt.% B4C/Al composites in their forged, extruded, and heat-treated states. We also examined how these states affect high-temperature mechanical properties and thermal conductivity. The results indicate that applying hot extrusion deformation along with optimized heat treatment parameters (500 °C for 24 h) allows for a lamellar dispersion of nano-Al2O3 and a crystallographic transition from amorphous to γ-phase. As a result, the composite demonstrates a tensile strength of 144 MPa and an enhanced thermal conductivity of 181 W/(m·K) at 350 °C. These findings provide theoretical insights and technical support for ensuring the high density and long-term safety of spent fuel storage materials. Full article
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11 pages, 480 KB  
Article
A Novel Deep Learning Model for Predicting Colorectal Anastomotic Leakage: A Pioneer Multicenter Transatlantic Study
by Miguel Mascarenhas, Francisco Mendes, Filipa Fonseca, Eduardo Carvalho, Andre Santos, Daniela Cavadas, Guilherme Barbosa, Antonio Pinto da Costa, Miguel Martins, Abdullah Bunaiyan, Maísa Vasconcelos, Marley Ribeiro Feitosa, Shay Willoughby, Shakil Ahmed, Muhammad Ahsan Javed, Nilza Ramião, Guilherme Macedo and Manuel Limbert
J. Clin. Med. 2025, 14(15), 5462; https://doi.org/10.3390/jcm14155462 - 3 Aug 2025
Viewed by 522
Abstract
Background/Objectives: Colorectal anastomotic leak (CAL) is one of the most severe postoperative complications in colorectal surgery, impacting patient morbidity and mortality. Current risk assessment methods rely on clinical and intraoperative factors, but no real-time predictive tool exists. This study aimed to develop [...] Read more.
Background/Objectives: Colorectal anastomotic leak (CAL) is one of the most severe postoperative complications in colorectal surgery, impacting patient morbidity and mortality. Current risk assessment methods rely on clinical and intraoperative factors, but no real-time predictive tool exists. This study aimed to develop an artificial intelligence model based on intraoperative laparoscopic recording of the anastomosis for CAL prediction. Methods: A convolutional neural network (CNN) was trained with annotated frames from colorectal surgery videos across three international high-volume centers (Instituto Português de Oncologia de Lisboa, Hospital das Clínicas de Ribeirão Preto, and Royal Liverpool University Hospital). The dataset included a total of 5356 frames from 26 patients, 2007 with CAL and 3349 showing normal anastomosis. Four CNN architectures (EfficientNetB0, EfficientNetB7, ResNet50, and MobileNetV2) were tested. The models’ performance was evaluated using their sensitivity, specificity, accuracy, and area under the receiver operating characteristic (AUROC) curve. Heatmaps were generated to identify key image regions influencing predictions. Results: The best-performing model achieved an accuracy of 99.6%, AUROC of 99.6%, sensitivity of 99.2%, specificity of 100.0%, PPV of 100.0%, and NPV of 98.9%. The model reliably identified CAL-positive frames and provided visual explanations through heatmaps. Conclusions: To our knowledge, this is the first AI model developed to predict CAL using intraoperative video analysis. Its accuracy suggests the potential to redefine surgical decision-making by providing real-time risk assessment. Further refinement with a larger dataset and diverse surgical techniques could enable intraoperative interventions to prevent CAL before it occurs, marking a paradigm shift in colorectal surgery. Full article
(This article belongs to the Special Issue Updates in Digestive Diseases and Endoscopy)
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16 pages, 2014 KB  
Article
CALB Immobilized on Octyl-Agarose—An Efficient Pharmaceutical Biocatalyst for Transesterification in Organic Medium
by Joanna Siódmiak, Jacek Dulęba, Natalia Kocot, Rafał Mastalerz, Gudmundur G. Haraldsson and Tomasz Siódmiak
Int. J. Mol. Sci. 2025, 26(14), 6961; https://doi.org/10.3390/ijms26146961 - 20 Jul 2025
Viewed by 461
Abstract
The growing need for developing safer and more effective methods for obtaining enantiomers of chiral compounds, particularly those with pharmacological activity, highlights the potential of biocatalysis as an appropriate pharmaceutical research direction. However, low catalytic activity and stability of free enzymes are often [...] Read more.
The growing need for developing safer and more effective methods for obtaining enantiomers of chiral compounds, particularly those with pharmacological activity, highlights the potential of biocatalysis as an appropriate pharmaceutical research direction. However, low catalytic activity and stability of free enzymes are often among the substantial limitations to the wide application of biocatalysis. Therefore, to overcome these obstacles, new technological procedures are being designed. In this study, we present optimized protocols for the immobilization of Candida antarctica lipase B (CALB) on an octyl- agarose support, ensuring high enantioselectivity in an organic reaction medium. The immobilization procedures (with drying step), including buffers with different pH values and concentrations, as well as the study of the influence of temperature and immobilization time, were presented. It was found that the optimal conditions were provided by citrate buffer with a pH of 4 and a concentration of 300 mM. The immobilized CALB on the octyl-agarose support exhibited high catalytic activity in the kinetic resolution of (R,S)-1-phenylethanol via enantioselective transesterification with isopropenyl acetate in 1,2-dichloropropane (DCP), as a model reaction for lipase activity monitoring on an analytical scale. HPLC analysis demonstrated that the (R)-1-phenylethyl acetate was obtained in an enantiomeric excess of eep > 99% at a conversion of approximately 40%, and the enantiomeric ratio was E > 200. Thermal and storage stability studies performed on the immobilized CALB octyl-agarose support confirmed its excellent stability. After 7 days of thermal stability testing at 65 °C in a climatic chamber, the (R)-1-phenylethyl acetate was characterized by enantiomeric excess of eep > 99% at a conversion of around 40% (similar values of catalytic parameters to those achieved using a non-stored lipase). The documented high catalytic activity and stability of the developed CALB-octyl-agarose support allow us to consider it as a useful tool for enantioselective transesterification in organic medium. Full article
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17 pages, 2044 KB  
Systematic Review
Clinical, Microbiological, and Biochemical Outcomes of Hyaluronic Acid in Non-Surgical Periodontal Therapy: A Systematic Review and Meta-Analysis
by Alessia Pardo, Veronica Magnani, Pietro Montagna, Andrea Ala, Gabriele Brancato, Federica Melloni, Giorgio Lombardo and Daniele De Santis
Appl. Sci. 2025, 15(11), 5975; https://doi.org/10.3390/app15115975 - 26 May 2025
Viewed by 1021
Abstract
Aim: This systematic review and meta-analysis evaluated the adjunctive use of hyaluronic acid (HA) in non-surgical periodontal therapy to improve clinical outcomes in patients with moderate-to-severe chronic periodontitis. The aim was to assess its effectiveness in reducing probing pocket depth (PPD), improving clinical [...] Read more.
Aim: This systematic review and meta-analysis evaluated the adjunctive use of hyaluronic acid (HA) in non-surgical periodontal therapy to improve clinical outcomes in patients with moderate-to-severe chronic periodontitis. The aim was to assess its effectiveness in reducing probing pocket depth (PPD), improving clinical attachment level (CAL), and decreasing bleeding on probing (BOP). Methods: Four electronic databases were searched (PubMed, Cochrane Library, Scopus, Web of Science, Grey Literature) for randomized controlled trials (RCTs) published until January 2025 and involving otherwise healthy patients treated with scaling and root planing (SRP) plus HA after at least 12 weeks of follow-up. Risk of bias was assessed using RoB 2.0; data were collected on clinical assessment, microbiological, and biochemical analysis and then analyzed using a fixed-effects or random-effects model considering the high heterogeneity of the included studies, which calls for caution when interpreting the results. Results: Fourteen of the 21 RCTs reviewed underwent a meta-analysis. Compared with SRP alone, the addition of adjunctive HA ≥ 0.8% led to an improvement in PPD, but the reduction in BOP was less consistent. Biochemical markers indicated less inflammation, oxidative stress, and selective antimicrobial activity. Although studies on 0.2% HA are still limited, improvements have been observed in clinical parameters, along with better biochemical and microbiological outcomes in the experimental group compared to the control group. Conclusions: Despite moderate heterogeneity and methodological limitations, the evidence supports the use of HA combined with SRP in periodontal treatment. Full article
(This article belongs to the Section Applied Dentistry and Oral Sciences)
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13 pages, 1023 KB  
Article
Hydroxytyrosyl Eicosapentaenoate as a Potential Antioxidant for Omega-3 Fatty Acids: Improved Synthesis and Comparative Evaluation with Other Natural Antioxidants
by Natalia García-Acosta, Rosa Cert, Marta Jordán, Luis Goya, Raquel Mateos and Jose Luis Espartero
Biomolecules 2025, 15(5), 714; https://doi.org/10.3390/biom15050714 - 13 May 2025
Viewed by 762
Abstract
Hydroxytyrosol (HT), the primary phenolic compound in virgin olive oil, has notable cardiovascular benefits, particularly in preventing low-density lipoprotein (LDL) oxidation. However, its hydrophilicity limits its solubility and integration into lipid-based formulations. This study aimed to enhance its lipophilicity by synthesizing hydroxytyrosyl eicosapentaenoate [...] Read more.
Hydroxytyrosol (HT), the primary phenolic compound in virgin olive oil, has notable cardiovascular benefits, particularly in preventing low-density lipoprotein (LDL) oxidation. However, its hydrophilicity limits its solubility and integration into lipid-based formulations. This study aimed to enhance its lipophilicity by synthesizing hydroxytyrosyl eicosapentaenoate (HT-EPA), a derivative of HT and eicosapentaenoic acid (EPA), using a one-step enzymatic catalysis with lipase B from Candida antarctica (CALB). The reaction, performed as a suspension of HT in ethyl eicosapentaenoate (Et-EPA) (1:9 molar ratio) under vacuum, achieved higher yields and shorter reaction times than previously reported, with a purity exceeding 98%, confirmed by 1H-NMR. For the first time, the antioxidant capacity of HT-EPA in comparison with other natural antioxidants was assessed using the FRAP assay, while its oxidative stability in an omega-3-rich oil matrix was evaluated via the Rancimat method. HT-EPA and hydroxytyrosyl acetate (HT-Ac) displayed antioxidant activity comparable to HT but significantly higher than α-tocopherol, a common food antioxidant. Given the scarcity of effective lipid-soluble antioxidants, HT-EPA represents a promising candidate for omega-3 nutraceuticals, offering enhanced stability and potential health benefits. This study provides a simple, efficient, and scalable strategy for developing functional lipid-based formulations with cardioprotective potential by improving HT solubility while preserving its antioxidant properties. Full article
(This article belongs to the Section Lipids)
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10 pages, 247 KB  
Article
Changes in Gingival Crevicular Fluid Endocan (ESM-1) Levels as a Potential Biomarker After Non-Surgical Periodontal Treatment in Periodontitis Patients
by Bilge Karci and Kevser Sokmen
Biomedicines 2025, 13(5), 1159; https://doi.org/10.3390/biomedicines13051159 - 9 May 2025
Viewed by 634
Abstract
Background: This study aimed to investigate endocan (ESM-1) levels in periodontitis patients before and after non-surgical periodontal treatment by analyzing the relationship between vascular endothelial growth factor A (VEGF-A) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF). Methods: This [...] Read more.
Background: This study aimed to investigate endocan (ESM-1) levels in periodontitis patients before and after non-surgical periodontal treatment by analyzing the relationship between vascular endothelial growth factor A (VEGF-A) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF). Methods: This study included 26 periodontally healthy people as controls (Group 1) and 27 patients with Stage III-Grade B periodontitis (Group 2). Demographic and periodontal variables were assessed. GCF samples were collected from every subject both before and 6 weeks following non-surgical periodontal therapy (NSPT). Using an enzyme-linked immunosorbent test, biomarker levels were determined. Results: The periodontitis patients showed higher ESM-1 levels than the controls, although the difference was not significant (p > 0.005). The ESM-1 levels decreased significantly after treatment (p = 0.001). The VEGF-A levels did not differ significantly between the periodontitis patients and controls (p > 0.005) and decreased non-significantly following treatment (p > 0.005). The TNF-α levels were significantly higher in the periodontitis patients than the controls (p = 0.000) and decreased significantly after treatment (p = 0.000). A significant correlation was found between TNF-α and both probing depth (PD) and interproximal clinical attachment level (iCAL) in the control group (p < 0.05). In the periodontitis group, the VEGF levels were significantly correlated with the gingival index (GI) (p < 0.05). Significant correlations were identified between ESM-1 and VEGF-A and ESM-1 and TNF-α, as well as VEGF-A and TNF-α, in both the control group and following treatment (p < 0.05). Conclusions: ESM-1 and TNF-α levels decreased with non-surgical periodontal treatment in GCF. Within the limits of the study, the findings suggest that ESM-1 levels in periodontal tissues may be an indicator of periodontal disease. Full article
(This article belongs to the Special Issue Periodontal Disease and Periodontal Tissue Regeneration)
14 pages, 2029 KB  
Communication
The Effect of Poppy Oil on Egg Production and Calcium Metabolism in Japanese Quail
by Csaba Szabó, Xénia Ozsváth, Brigitta Csernus, Gabriella Gulyás, Márta Horváth, Levente Czeglédi, János Oláh, Nafiatur Rizqoh, Gabriele Achille and János Posta
Animals 2025, 15(9), 1348; https://doi.org/10.3390/ani15091348 - 7 May 2025
Viewed by 780
Abstract
Consumers tend to favor natural dietary supplements to improve their health. However, vendors rarely cite scientific evidence to justify these claims. In the case of poppy oil, it is often mentioned as having a positive effect on Ca metabolism-related disorders, but no proof [...] Read more.
Consumers tend to favor natural dietary supplements to improve their health. However, vendors rarely cite scientific evidence to justify these claims. In the case of poppy oil, it is often mentioned as having a positive effect on Ca metabolism-related disorders, but no proof has been provided. Therefore, the aim of our trial was to test the possible effect of poppy oil on calcium metabolism using Japanese quail layers as a model animal. A total of 120 four-week-old quail were divided into three dietary treatments (four cages per treatment, with ten birds in each cage): a control group (using sunflower oil as the energy source in the diet), 0.5%, and 1% poppy oil supplementation (replacing sunflower oil). Egg production, eggshell thickness, eggshell strength, and egg yolk color were investigated. Ca retention was determined using the acid-insoluble ash method. At the end of the experiment, two birds per cage were sacrificed, and uterus and jejunum samples were collected for gene expression analyses. Poppy oil supplementation improved egg production in terms of intensity, egg weight, and eggmass production. The thickness and eggshell strength decreased when 1% poppy oil was fed to the animals, while Ca retention improved. Poppy oil supplementation increased the expression of Ca transporter genes (CALB1, SLC8A1, and SLC26A9) in the uterus and ITPR1 in the jejunum. Our results indicate a possible effect of poppy oil on Ca metabolism. Further studies are needed to identify the active compound and to understand the mode of action. Full article
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15 pages, 21648 KB  
Article
Fungal Pathogens of Peach Palm Leaf Spot in Thailand and Their Fungicide Sensitivity
by Prisana Wonglom, Nakarin Suwannarach, Jaturong Kumla and Anurag Sunpapao
J. Fungi 2025, 11(4), 318; https://doi.org/10.3390/jof11040318 - 17 Apr 2025
Cited by 1 | Viewed by 578
Abstract
Peach palm (Bactris gasipaes Kunth) is a long-lived tropical palm valued for its edible, nutritious fruits. The cultivation area of peach palm, which was introduced to Thailand for fruit production, has been steadily expanding. Small brown spots that expanded into irregular lesions [...] Read more.
Peach palm (Bactris gasipaes Kunth) is a long-lived tropical palm valued for its edible, nutritious fruits. The cultivation area of peach palm, which was introduced to Thailand for fruit production, has been steadily expanding. Small brown spots that expanded into irregular lesions with dark margins were first observed on B. gasipaes seedlings in commercial nurseries in Phetchaburi Province, southern Thailand. To identify the causal pathogens, ten fungal isolates were obtained from symptomatic leaves and subjected to pathogenicity tests, confirming their ability to cause the disease. Morphological and molecular analyses identified five isolates as Colletotrichum fructicola (BGC02.2, BGC03) and C. theobromicola (BGC01, BGC02.1, BGC04) and five isolates as Fusarium pernambucanum (BGF01, BGF02, BGF03, BGF04.1, BGF04.2). Phylogenetic analysis was based on act, cal, gapdh, ITS, and tub2 regions for Colletotrichum spp. and cal, rpb2, and tef1-α for Fusarium spp. In vitro fungicide assays revealed that C. fructicola and C. theobromicola were the most sensitive to carbendazim, mancozeb, and prochloraz, while F. pernambucanum was effectively inhibited by mancozeb and prochloraz. This study represents the first report of C. fructicola, C. theobromicola, and F. pernambucanum causing leaf spot disease on B. gasipaes in Thailand, providing essential insights for disease management strategies in the region. Full article
(This article belongs to the Special Issue Diversity of Microscopic Fungi)
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17 pages, 1547 KB  
Article
Green Biocatalysis of Xylitol Monoferulate: Candida antarctica Lipase B-Mediated Synthesis and Characterization of Novel Bifunctional Prodrug
by Federico Zappaterra, Francesco Presini, Domenico Meola, Chaimae Chaibi, Simona Aprile, Lindomar Alberto Lerin and Pier Paolo Giovannini
BioTech 2025, 14(2), 25; https://doi.org/10.3390/biotech14020025 - 2 Apr 2025
Viewed by 924
Abstract
Natural compounds with significant bioactive properties can be found in abundance within biomasses. Especially prominent for their anti-inflammatory, neuroprotective, antibacterial, and antioxidant activities are cinnamic acid derivatives (CAs). Ferulic acid (FA), a widely studied phenylpropanoid, exhibits a broad range of therapeutic and nutraceutical [...] Read more.
Natural compounds with significant bioactive properties can be found in abundance within biomasses. Especially prominent for their anti-inflammatory, neuroprotective, antibacterial, and antioxidant activities are cinnamic acid derivatives (CAs). Ferulic acid (FA), a widely studied phenylpropanoid, exhibits a broad range of therapeutic and nutraceutical applications, demonstrating antidiabetic, anticancer, antimicrobial, and hepato- and neuroprotective activities. This research investigates the green enzymatic synthesis of innovative and potentially bifunctional prodrug derivatives of FA, designed to enhance solubility and stability profiles. Selective esterification was employed to conjugate FA with xylitol, a biobased polyol recognized for its bioactive antioxidant properties and safety profile. Furthermore, by exploiting t-amyl alcohol as a green solvent, the enzymatic synthesis of the derivative was optimized for reaction parameters including temperature, reaction time, enzyme concentration, and molar ratio. The synthesized derivative, xylitol monoferulate (XMF), represents a novel contribution to the literature. The comprehensive characterization of this compound was achieved using advanced spectroscopic methods, including 1H-NMR, 13C-NMR, COSY, HSQC, and HMBC. This study represents a significant advancement in the enzymatic synthesis of high-value biobased derivatives, demonstrating increased biological activities and setting the stage for future applications in green chemistry and the sustainable production of bioactive compounds. Full article
(This article belongs to the Section Industry, Agriculture and Food Biotechnology)
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23 pages, 970 KB  
Article
Synthesis of Enantiostructured Triacylglycerol Prodrugs Constituting an Active Drug Located at Terminal sn-1 and sn-3 Positions of the Glycerol Backbone
by Lena Rós Jónsdottir and Gudmundur G. Haraldsson
Molecules 2025, 30(5), 991; https://doi.org/10.3390/molecules30050991 - 21 Feb 2025
Viewed by 673
Abstract
The current paper reports the asymmetric synthesis of a focused library of enantiostructured triacylglycerols (TAGs) constituting a potent drug of the NSAID type (ibuprofen or naproxen) along with a pure bioactive n-3 polyunsaturated fatty acid (PUFA) intended as a novel type of prodrug. [...] Read more.
The current paper reports the asymmetric synthesis of a focused library of enantiostructured triacylglycerols (TAGs) constituting a potent drug of the NSAID type (ibuprofen or naproxen) along with a pure bioactive n-3 polyunsaturated fatty acid (PUFA) intended as a novel type of prodrug. In this second category, a TAG prodrug of the terminal sn-1 or sn-3 position of the glycerol skeleton is acylated with a single saturated medium-chain fatty acid (C6, C8, C10, or C12), and another with the drug entity; the PUFA (EPA or DHA) is located in the sn-2 position. This was accomplished by a six-step chemoenzymatic approach, two of which were promoted by a lipase, starting from enantiopure (R)- and (S)-solketals. The highly regioselective immobilized Candida antarctica lipase (CAL-B) played a crucial role in the regiocontrol of the synthesis. The most challenging key step involved the incorporation of the drugs that were activated as oxime esters by the lipase exclusively in the terminal position of glycerol that is protected as a benzyl ether. All combinations, a total of 32 such prodrug TAGs, were prepared, isolated, and fully characterized, along with 24 acylglycerol intermediates, obtained in very-high-to-excellent yields in the majority of cases. Full article
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24 pages, 3136 KB  
Article
Candidate Key Proteins in Tinnitus—A Bioinformatic Study of Synaptic Transmission in the Inferior Colliculus
by Johann Gross, Marlies Knipper and Birgit Mazurek
Int. J. Mol. Sci. 2025, 26(5), 1831; https://doi.org/10.3390/ijms26051831 - 20 Feb 2025
Cited by 1 | Viewed by 1143
Abstract
Proteins involved in synaptic transmission in normal hearing, acoustic stimulation, and tinnitus were identified using protein–protein interaction (PPI) networks. The gene list for tinnitus was compiled from the GeneCards database using the keywords “synaptic transmission” AND “inferior colliculus” AND “tinnitus” (Tin). For comparison, [...] Read more.
Proteins involved in synaptic transmission in normal hearing, acoustic stimulation, and tinnitus were identified using protein–protein interaction (PPI) networks. The gene list for tinnitus was compiled from the GeneCards database using the keywords “synaptic transmission” AND “inferior colliculus” AND “tinnitus” (Tin). For comparison, two gene lists were built using the keywords “auditory perception” (AP) and “acoustic stimulation” (AS). The STRING and the Cytoscape data analyzer were used to identify the top two high-degree proteins (HDPs) and the corresponding high-score interaction proteins (HSIP). The top1 key proteins of the AP and AS processes are BDNF and the receptor NTRK2; the top2 key proteins in the AP process are PVALB, together with GAD1, CALB1, and CALB2, which are important for the balance of excitation and inhibition. In the AS process, the top2 key proteins are FOS, CREB1, EGR1, and MAPK1, reflecting an activated state. The top1 key proteins of the Tin process are BDNF, NTRK3, and NTF3; these proteins are associated with the proliferation and differentiation of neurons and indicate the remodeling of synaptic transmission in IC. The top2 key proteins are GFAP and S100B, indicating a role for astrocytes in the modulation of synaptic transmission. Full article
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35 pages, 7587 KB  
Article
Design, Synthesis and Bioactive Evaluation of Topo I/c-MYC Dual Inhibitors to Inhibit Oral Cancer via Regulating the PI3K/AKT/NF-κB Signaling Pathway
by Bin Zheng, Yi-Xiao Wang, Zi-Yan Wu, Xin-Wei Li, Li-Qing Qin, Nan-Ying Chen, Gui-Fa Su, Jun-Cheng Su and Cheng-Xue Pan
Molecules 2025, 30(4), 894; https://doi.org/10.3390/molecules30040894 - 14 Feb 2025
Cited by 2 | Viewed by 1075
Abstract
The significantly rising incidence of oral cancer worldwide urgently requires the identification of novel, effective molecular targets to inhibit the progression of malignancy. DNA topoisomerase I (Topo I) is a well-established target for cancer treatment, and many studies have shown that different cancer [...] Read more.
The significantly rising incidence of oral cancer worldwide urgently requires the identification of novel, effective molecular targets to inhibit the progression of malignancy. DNA topoisomerase I (Topo I) is a well-established target for cancer treatment, and many studies have shown that different cancer cell genes could be targeted more selectively with one type of Topo I inhibitor. In this report, a new scaffold pyridothieno[3,2-c]isoquinoline 11,11-dioxide was designed via the combination of the key fragment or bioisoster of Topo I inhibitor azaindenoisoquinolines and G-quadruplex binder quindoline. Thirty-two target derivatives were synthesized, among which compounds 7be, with potent Topo I inhibition, exhibited effective antiproliferative activity against Cal27, one of the oral cancer cell lines highly expressing Topo I protein. Further studies indicated that 7be could also inhibit the activation of PI3K/AKT/NF-κB pathway and downregulate the level of c-MYC, repress the colony formation and the migration of Cal27 cells and trigger apoptosis and autophagy. Molecular docking indicated that 7be could interact with the complex of Topo I and DNA via a mode similar to the indenoisoquinolines. The results of the Cal27 xenograft model confirmed that 7be exhibited promising anticancer efficacy in vivo, with tumor growth inhibition (TGI) of 64.7% at 20 mg/kg. Full article
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16 pages, 2599 KB  
Article
Vitamin D Receptor and CYP450 Enzyme Dysregulation May Mediate Oral Cancer Responsiveness
by Dustin Hunsaker, James Landon Moore, Katherine M. Howard and Karl Kingsley
Targets 2025, 3(1), 6; https://doi.org/10.3390/targets3010006 - 8 Feb 2025
Viewed by 799
Abstract
Many health benefits are associated with Vitamin D (VitD), although deficiency is associated with poor health outcomes and the increased risk of cancer development. For example, many tissue-specific enzymes are involved in VitD metabolism, and mutations or deletions within Vitamin D receptor (VDR) [...] Read more.
Many health benefits are associated with Vitamin D (VitD), although deficiency is associated with poor health outcomes and the increased risk of cancer development. For example, many tissue-specific enzymes are involved in VitD metabolism, and mutations or deletions within Vitamin D receptor (VDR) genes are known to increase the cancer risk by altering their functions or bioavailability, although less is known about these phenomena in oral cancers. Using well-characterized, commercially available oral cell lines (OKF4, HGF-1, SCC4, SCC9, SCC15, SCC25, and CAL27), the mRNA expression of P450 cytochrome VitD metabolic enzymes and receptor genes by qPCR revealed differential results. One oral cancer line (SCC15) did not express either the Vitamin D receptor (VDR) or FOK1 polymorphism and was also least affected by VitD3 administration in growth assays. In contrast, most oral cancers were missing one or more hydrolase (CYP2R1 and CYP24A1) or hydrolate (CYP27A1 and CYP27B1) enzymes. SCC25 was missing both the hydrolate enzymes and was the most inhibited in the VitD3 growth assays, while SCC4 was missing both the hydroxylase enzymes and was the least inhibited by VitD2. These associations between mRNA expression (or lack thereof) and VitD3 and VitD2 responsiveness can be used to identify molecular targets, which may lead to effective screening tools for VitD-related, complementary and alternative therapies. Full article
(This article belongs to the Special Issue Multidisciplinary Approach to Oral Cavity Cancer: A Hard Enemy)
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21 pages, 15410 KB  
Article
Paleoclimatic Events Since 25 kyr B.P. and the Regional Differences Documented by Phytoliths in the Central Songnen Plain, NE China
by Yaran Li, Xinrong Zhang, Jiayu Wang, Shi Fang, Yuanbo Huo and Jiakang Liu
Forests 2025, 16(2), 275; https://doi.org/10.3390/f16020275 - 6 Feb 2025
Viewed by 808
Abstract
Identification of paleoclimate oscillation from various climate proxies across different regions is important for the mechanistic research of paleoclimate. Phytoliths from the lacustrine sediment of central NE China were extracted for paleoclimate reconstruction and abrupt event recognition. The combined phytolith assemblages; indices of [...] Read more.
Identification of paleoclimate oscillation from various climate proxies across different regions is important for the mechanistic research of paleoclimate. Phytoliths from the lacustrine sediment of central NE China were extracted for paleoclimate reconstruction and abrupt event recognition. The combined phytolith assemblages; indices of Iw, Iph, D/P, Pi/P, and T/P; and the 66.4% PCA information with 95% confidence ellipse showed six global synchronously paleo-stages in the past 25,000 years: mixed coniferous broadleaf forest in a semi-humid cool climate (25,165–22,180 cal aB.P.), cold and arid steppe (22,180–18,080 cal aB.P.), semi-humid and semi-arid steppe (18,080–11,380); semi-humid cool grassland (11,380–7790 cal aB.P.), humid warm forest steppe (7790–4300 cal aB.P.), and semi-arid and cool meadow steppe (4300 cal aB.P. to the present). The global abrupt events of the 4.2-kiloyear event, 8.2-kiloyear event, Younger Dryas (YD), Heinrich1 (H1), and Heinrich2 (H2) were also captured by phytolith indices. The regional character of the reduction in humidity of the YD might have been affected by the combined influence of the Okhotsk High and the surrounding mountains. These findings not only strengthen phytolith palaeoresearch but also provide basic information for the mechanistic research of palaeoclimate in the edge area of Northeast Asia and promote global climate change research. Full article
(This article belongs to the Section Forest Ecology and Management)
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