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22 pages, 3176 KiB  
Article
Maresin 2, a Specialized Pro-Resolution Lipid Mediator, Reduces Pain and Inflammation Induced by Bothrops jararaca Venom in Mice
by Kassyo L. S. Dantas, Beatriz H. S. Bianchini, Matheus D. V. da Silva, Maiara Piva, Joice M. da Cunha, Janaina M. Zanoveli, Fernanda C. Cardoso, Fabiana T. M. C. Vicentini, Camila R. Ferraz, Patricia B. Clissa, Rubia Casagrande and Waldiceu A. Verri
Toxins 2025, 17(8), 367; https://doi.org/10.3390/toxins17080367 - 25 Jul 2025
Viewed by 304
Abstract
The venom of Bothrops jararaca (BjV) induces intense and prolonged pain, which is not alleviated by antivenom, along with hemorrhage and inflammation. In this study, we investigated the effects of the specialized pro-resolving lipid mediator (SPM) maresin 2 (MaR2) in a murine model [...] Read more.
The venom of Bothrops jararaca (BjV) induces intense and prolonged pain, which is not alleviated by antivenom, along with hemorrhage and inflammation. In this study, we investigated the effects of the specialized pro-resolving lipid mediator (SPM) maresin 2 (MaR2) in a murine model of BjV-evoked pain and inflammation. Mice received a single intraperitoneal (i.p.) injection of MaR2 30 min before the intraplantar BjV injection. MaR2 treatment significantly attenuated mechanical (electronic aesthesiometer) and thermal (hot plate) hyperalgesia in a dose-dependent manner. Additionally, MaR2 restored the balance for the hind-paw static weight distribution. When BjV (0.01, 0.1, and 1 μg) stimulus was administered intraperitoneally, pre-treatment with MaR2 (0.3, 1, or 3 ng) ameliorated mechanical and thermal hyperalgesia in a dose-dependent manner. Moreover, MaR2 (3 ng) effectively reduced the levels of myeloperoxidase activity and cytokines (TNF-α, IL-1β, and IL-6) and superoxide anion (O2•−) production induced by intraplantar injection of BjV while enhancing total antioxidant levels (ABTS scavenging). For the peritonitis model induced by BjV, MaR2 pretreatment decreased leukocyte recruitment, hemorrhage, nitric oxide (NO), and O2•− generation and gp91phox and inducible nitric oxide synthase (iNOS) mRNA expression. In conclusion, this study presents the first evidence that MaR2 effectively mitigated BjV-induced pain, hemorrhage, and inflammation. Full article
(This article belongs to the Section Animal Venoms)
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31 pages, 7931 KiB  
Article
Enhanced Pool Boiling via Binder-Jetting 3D-Printed Porous Copper Structures: CHF and HTC Investigation
by Lilian Aketch Okwiri, Takeshi Mochizuki, Kairi Koito, Noriaki Fukui and Koji Enoki
Appl. Sci. 2025, 15(14), 7892; https://doi.org/10.3390/app15147892 - 15 Jul 2025
Viewed by 261
Abstract
The escalating heat flux densities in high-performance electronics necessitate superior thermal management. This study enhanced pool-boiling heat transfer, a method offering high heat removal capacity, by leveraging Binder Jetting 3D Printing (BJ3DP) to create complex porous copper structures without the need for chemical [...] Read more.
The escalating heat flux densities in high-performance electronics necessitate superior thermal management. This study enhanced pool-boiling heat transfer, a method offering high heat removal capacity, by leveraging Binder Jetting 3D Printing (BJ3DP) to create complex porous copper structures without the need for chemical treatments. This approach enables a reliable utilization of phenomena like capillarity for improved performance. Three types of porous copper structures, namely Large Lattice, Small Lattice, and Staggered, were fabricated on pure copper substrates and tested via pool boiling of de-ionized and de-gassed water at atmospheric pressure. Compared to a plain polished copper surface, which exhibited a critical heat flux (CHF) of 782 kW/m2 at a wall superheat of 18 K, the 3D-printed porous copper surfaces showed significantly improved heat transfer performance. The Staggered surface achieved a conventional CHF of 2342.4 kW/m2 (a 199.7% enhancement) at a wall superheat of 24.6 K. Notably, the Large Lattice and Small Lattice structures demonstrated exceptionally stable boiling without reaching the typical catastrophic CHF within the experimental parameters. These geometries continued to increase in heat flux, reaching maximums of 2397.7 kW/m2 (206.8% higher at a wall superheat of 55.6 K) and 2577.2 kW/m2 (229.7% higher at a wall superheat of 39.5 K), respectively. Subsequently, a gradual decline in heat flux was observed with an increasing wall superheat, demonstrating an outstanding resistance to the boiling crisis. These improvements are attributed to the formation of distinct vapor–liquid pathways within the porous structures, which promotes the efficient rewetting of the heated surface through capillary action. This mechanism supports a highly efficient, self-sustaining boiling configuration, emphasizing the superior rewetting and vapor management capabilities of these 3D-printed porous structures, which extend the boundaries of sustained high heat flux performance. The porous surfaces also demonstrated a higher heat transfer coefficient (HTC), particularly at lower heat fluxes (≤750 kW/m2). High-speed digital camera visualization provided further insight into the boiling phenomenon. Overall, the findings demonstrate that these BJ3DP structured surfaces produce optimized vapor–liquid pathways and capillary-enhanced rewetting, offering significantly superior heat transfer performance compared to smooth surfaces and highlighting their potential for advanced thermal management. Full article
(This article belongs to the Section Energy Science and Technology)
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21 pages, 3380 KiB  
Article
Purification, Structural Characterization, and Immunomodulatory Activity of an Exopolysaccharide from Acetilactobacillus jinshanensis BJ01 in Baijiu Fermentation Grains
by Tian Tian, Bo Wan, Ying Xiong, Han Wang, Yuanyuan An, Ruijie Gao, Pulin Liu, Mingchun Zhang, Lihong Miao and Weifang Liao
Foods 2025, 14(13), 2162; https://doi.org/10.3390/foods14132162 - 20 Jun 2025
Viewed by 434
Abstract
This study aims to identify the chemical structure and immunomodulatory activity of exopolysaccharides (EPSs) from Acetilactobacillus jinshanensis BJ01 and suggest its potential applications in the pharmaceutical field and as functional food additives. The EPS-1 produced by A. jinshanensis BJ01 was purified using [...] Read more.
This study aims to identify the chemical structure and immunomodulatory activity of exopolysaccharides (EPSs) from Acetilactobacillus jinshanensis BJ01 and suggest its potential applications in the pharmaceutical field and as functional food additives. The EPS-1 produced by A. jinshanensis BJ01 was purified using column chromatography. The lyophilized powder obtained by vacuum freeze-drying was used for structural characterization and immunomodulatory activity analysis. Gel permeation chromatography (GPC) determined its molecular weight as 156.58 kDa. High-performance anion-exchange chromatography (HPAEC) identified that the EPS-1 is composed of mannose, xylose, and glucose. The structural characterization of EPS-1 by gas chromatography–mass spectrometry (GC-MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopy demonstrated that EPS-1 is primarily composed of α-D-Manp-(1→, →2,6)-α-D-Manp-(1→, →2)-α-D-Manp-(1→, and →3)-α-D-Manp-(1→. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) illustrated that EPS-1 exhibited a round, flake-like morphology. In vitro experiments with RAW264.7 macrophages demonstrated the high immunomodulatory activity of EPS-1. Significant upregulation of iNOS, IL-6, and TNF-α mRNA levels was confirmed by qRT-PCR (p < 0.05). Western blotting revealed that EPS-1 (6.25 μg/mL) induced phosphorylation of NF-κB (p65, IκBα) and MAPK (ERK) signaling proteins. This study provides the first structural and immunomodulatory characterization of an exopolysaccharide from A. jinshanensis BJ01, highlighting its potential as a novel immune adjuvant. Full article
(This article belongs to the Section Food Nutrition)
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16 pages, 2053 KiB  
Article
The Impact of Seasonality on Air Quality in Terms of Pollution with Substances Hazardous to the Environment
by Małgorzata Kida and Sabina Ziembowicz
Appl. Sci. 2025, 15(12), 6551; https://doi.org/10.3390/app15126551 - 10 Jun 2025
Viewed by 459
Abstract
The study presents an analysis of the concentrations of polycyclic aromatic hydrocarbons (PAHs) and particulate matter with a diameter of less than 10 µm (PM10) in the air across various locations, as well as their impact on human health. Research in [...] Read more.
The study presents an analysis of the concentrations of polycyclic aromatic hydrocarbons (PAHs) and particulate matter with a diameter of less than 10 µm (PM10) in the air across various locations, as well as their impact on human health. Research in this area was conducted at eight stations as part of the national environmental monitoring system run in Poland by the Chief Inspectorate for Environmental Protection. Daily measurement data of PM10 and the concentrations of PAHs associated with these particles were analyzed for the period from January to December 2023. The results showed that pollutant concentrations in the atmosphere vary depending on location, season, and meteorological conditions. The highest concentrations were observed during the winter season, when the combustion of solid fuels increases, while the lowest concentrations were recorded in the summer. The total concentration of PAHs ranged from 0.35 to 34.50 ng/m3. The annual average concentration of PM10 at the analyzed stations was 19.29 ± 3.01 µg/m3. Principal component analysis indicated that PAHs in the air primarily originate from emissions related to transportation, biomass combustion, and industry. Furthermore, the estimated health risk, considering the Incremental Lifetime Cancer Risk (ILCR) index, showed that the risk of cancer associated with inhaling PAHs by children and adults did not exceed the permissible limits. The main contributor to the total carcinogenic activity of the PAH mixture was benzo(b)fluorantene (BbF) (31.5%), followed by benzo(a)pyrene (BaP) (5.5%), indeno(1,2,3-cd)pyrene (IP) (18.2%), benzo(j)fluorantene (BjF) (12.9%), benzo(k)fluorantene (BkF) (8.5%), benzo(a)anthracene (BaA) (2.5%), and dibenzo(a,h)anthracene (DBahA) (1.0%). Full article
(This article belongs to the Special Issue Advances in Air Pollution Detection and Air Quality Research)
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14 pages, 2086 KiB  
Article
Genetic Mapping of QTL Associated with 100-Kernel Weight Using a DH Population in Maize
by Huawei Li, Hao Li, Jian Chen, Xiangbo Zhang, Baobao Wang, Shujun Zhi, Haiying Guan, Weibin Song, Jinsheng Lai, Haiming Zhao and Rixin Gao
Plants 2025, 14(12), 1737; https://doi.org/10.3390/plants14121737 - 6 Jun 2025
Viewed by 503
Abstract
Grain yield establishment is a complex progress and the genetic basis of one of the most important yield components, 100-kernel weight, remains largely unknown. Here, we employed a double haploid (DH) population containing 477 lines which was developed from a cross of two [...] Read more.
Grain yield establishment is a complex progress and the genetic basis of one of the most important yield components, 100-kernel weight, remains largely unknown. Here, we employed a double haploid (DH) population containing 477 lines which was developed from a cross of two maize elite inbred lines, PHBA6 and Chang7-2, to identify quantitative trait loci (QTL) that related to 100-kernel weight. The phenotypes of the DH population were acquired over three years in two different locations, while the DH lines were genotyped by next-generation sequencing technology of massively parallel 3ʹ end RNA sequencing (MP3RNA-seq). Eventually, 28,874 SNPs from 436 DH lines were preserved after SNP calling and filtering and a genetic map with a length of 837 cM was constructed. Then, single environment QTL analysis was performed using the R/qtl program, and it was found that a total of 17 QTLs related to 100-kernel weight were identified and distributed across the whole genome except chromosomes 5 and 6. The total phenotypic variation explained by QTLs detected in three different environments (BJ2016, BJ2107, and HN2018) was 22.2%, 32.9%, and 51.38%, respectively. Among these QTLs, three of them were identified across different environments as environmentally stable QTLs and explained more than 10% of the phenotypic variance each. Together, the results provided in this study preliminarily revealed the genetic basis of 100-kernel weight and will enhance molecular breeding for key agronomic kernel-related traits in maize. Full article
(This article belongs to the Section Plant Genetics, Genomics and Biotechnology)
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24 pages, 2654 KiB  
Article
Short-Term Beetroot Juice Supplementation Enhances Strength, Reduces Fatigue, and Promotes Recovery in Physically Active Individuals: A Randomized, Double-Blind, Crossover Trial
by Atef Salem, Achraf Ammar, Mohamed Kerkeni, Mohamed Ali Boujelbane, Ayse Merve Uyar, Leonard Moritz Köbel, Saranya Selvaraj, Reza Zare, Katie M. Heinrich, Haitham Jahrami, Slim Tounsi, Piotr Zmijewski, Wolfgang I. Schöllhorn, Khaled Trabelsi and Hamdi Chtourou
Nutrients 2025, 17(10), 1720; https://doi.org/10.3390/nu17101720 - 19 May 2025
Viewed by 3672
Abstract
Background/Objectives: Beetroot juice (BJ), a natural source of dietary nitrate, has gained increasing attention for its potential to improve exercise performance and cardiovascular function. While its benefits are well documented in endurance contexts, less is known about its short-term effects on resistance training [...] Read more.
Background/Objectives: Beetroot juice (BJ), a natural source of dietary nitrate, has gained increasing attention for its potential to improve exercise performance and cardiovascular function. While its benefits are well documented in endurance contexts, less is known about its short-term effects on resistance training performance and recovery. Thus, this study investigated the effects of short-term BJ supplementation on strength performance, cardiovascular responses, muscle oxygenation, and post-exercise recovery in resistance-trained males. Methods: Twelve healthy men (age: 21.3 ± 1.9 years; body mass index: 21.42 ± 2.36 kg/m2) completed two supplementation protocols involving BJ, providing 450 mg of nitrate per day, and a nitrate-free placebo (PLA). Each protocol consisted of two laboratory visits, one to assess the acute ergogenic effects and another to evaluate recovery after 72 h, resulting in a total of four sessions over a two-week period. During the three consecutive days of supplementation, participants ingested a single 900 mL dose (15 g BJ powder/PLA) 2 h before the first session, followed by three daily 300 mL doses (5 g BJ each/PLA) over the next two days, and a final dose (15 g BJ powder/PLA) taken 2 h before the second session (72 h post-first session). Each testing session involved incremental back squat (BS) and bench press (BP) exercises at 60%, 70%, and 80% of the one-repetition maximum (1RM) performed to failure, with three-minute rest intervals between sets. Repetition to failure, movement velocity, peak power, peak heart rate (HR), and muscle oxygenation (SmO2) were recorded during BP and BS exercises. Heart rate variability (HRV) and blood lactate were assessed before and after each training session. Lower-limb strength (CMJ and SJ) and delayed-onset muscle soreness (DOMS) were assessed daily during the 3-day supplementation period. Results: BJ significantly increased repetitions completed at 80% 1RM during BP and BS (p < 0.05) compared to the PLA. Peak movement velocity improved across all intensities using BJ with higher values compared to the PLA at 60–80% 1RM (p < 0.05). SmO2 was higher in BJ at 70–80% 1RM) and further improved after 72 h of BJ supplementation (p < 0.05). Cardiovascular strain was reduced in BJ, evidenced by lower peak HRs and smaller post-exercise declines in HRV indices (p < 0.05). Post-exercise recovery favored BJ, with faster recovery in jump performance at 24 h and reduced upper-limb DOMS at 24–48 h (p < 0.05). Conclusions: Short-term BJ supplementation enhances high-intensity resistance performance, improves muscle oxygenation, attenuates cardiovascular strain, and accelerates neuromuscular recovery. These benefits highlight its potential as a practical strategy for athletes seeking to optimize training performance and recovery during periods of intense resistance training. Full article
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18 pages, 3075 KiB  
Article
Snake Venom Peptide Fractions from Bothrops jararaca and Daboia siamensis Exhibit Differential Neuroprotective Effects in Oxidative Stress-Induced Zebrafish Models
by Felipe Assumpção da Cunha e Silva, Brenda Rufino da Silva, Leticia Ribeiro de Barros, Emidio Beraldo-Neto, Adolfo Luis Almeida Maleski and Carlos Alberto-Silva
Pharmaceuticals 2025, 18(5), 678; https://doi.org/10.3390/ph18050678 - 2 May 2025
Cited by 1 | Viewed by 2785
Abstract
Introduction: Snake venoms are rich sources of bioactive peptides with therapeutic potential, particularly against neurodegenerative diseases linked to oxidative stress. While the peptide fraction (<10 kDa) from Bothrops jararaca venom has shown in vitro neuroprotection, analogous fractions from related species remain unexplored in vivo. [...] Read more.
Introduction: Snake venoms are rich sources of bioactive peptides with therapeutic potential, particularly against neurodegenerative diseases linked to oxidative stress. While the peptide fraction (<10 kDa) from Bothrops jararaca venom has shown in vitro neuroprotection, analogous fractions from related species remain unexplored in vivo. Methods: This study comparatively evaluated the neuroprotective effects of two peptide fractions (pf) from Daboia siamensis (pf-Ds) and B. jararaca (pf-Bj) against H2O2-induced oxidative stress using in vitro (PC12 cells) and in vivo (zebrafish, Danio rerio) models. Results: In vitro, pf-Ds (1 µg mL−1) did not protect PC12 cells against H2O2-induced cytotoxicity, unlike previously reported effects of pf-Bj. In vivo, neither pf-Ds nor pf-Bj (1–20 µg mL−1) induced significant developmental toxicity in zebrafish larvae up to 120 h post-fertilization (hpf). The neuroprotective effects of both pf were evaluated using two experimental models: (I) Larvae at 96 hpf were exposed to either pf-Ds or pf-Bj (10 µg mL−1) for 4 h, followed by co-exposure to H2O2 (0.2 mmol L−1) for an additional 10 h to induce oxidative stress (4–20 h model); (II) Embryos at 4 hpf were treated with pf-Ds or pf-Bj (10 µg mL−1) continuously until 96 hpf, after which they were exposed to H2O2 (0.2 mmol L−1) for another 24 h (96–120 h model). In a short-term treatment model, neither fraction reversed H2O2-induced deficits in metabolism or locomotor activity. However, in a prolonged treatment model, pf-Bj significantly reversed the H2O2-induced locomotor impairment, whereas pf-Ds did not confer protection. Conclusions: These findings demonstrate, for the first time, the in vivo neuroprotective potential of pf-Bj against oxidative stress-induced behavioral deficits in zebrafish, contingent on the treatment regimen. The differential effects between pf-Ds and pf-Bj highlight species-specific venom composition and underscore the value of zebrafish for evaluating venom-derived peptides. Full article
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12 pages, 4356 KiB  
Article
Unveiling the Impact of 0–20 Gpa Hydrostatic Pressure on the Physical Properties of (Cs2HfCl6) Double Perovskite
by Umar Farooq, Nabeel Israr, Belqees Hassan, Ali Alnakhlani, Mohamed Kallel, Wasif ur Rehman and Yong-Long Wang
Crystals 2025, 15(5), 395; https://doi.org/10.3390/cryst15050395 - 24 Apr 2025
Viewed by 376
Abstract
The current work determines the physical properties of Cs2HfCl6 photovoltaic compounds including their structural, electronic, and optical behavior, utilizing the DFT approach. The simulated Cs2HfCl6 lattice constants, cell volumes, and bond lengths decrease as the pressure increases [...] Read more.
The current work determines the physical properties of Cs2HfCl6 photovoltaic compounds including their structural, electronic, and optical behavior, utilizing the DFT approach. The simulated Cs2HfCl6 lattice constants, cell volumes, and bond lengths decrease as the pressure increases from 0 to 20 GPa. The band structure analysis reveals that the calculated under-pressure (0–20 GPa) of Cs2HfCl6 is semiconducting with a flexible indirect bandgap (5.44, 2.76, 2.02, 1.45, and 0.99) eV. The electronic bandgap diminishes (0–20 GPa), transitioning the compound from the UV to the visible spectra. This alteration improves the transition from the VBM to the CBM, hence augmenting the optical effectiveness. Concurrently, the dielectric function escalates, enhancing the absorption and conductivity, and causing a red shift in the optical spectra, while diminishing the reflection in the visible spectra. Our findings on the hydraulic pressure (0–20 GPa) and the electrical and optical properties indicate that Cs2HfCl6 may be utilized in the development of next-generation solar cells, LEDs, UV sensors, and high-pressure optical instruments. Full article
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29 pages, 1763 KiB  
Article
Energy-Efficient Secure Cell-Free Massive MIMO for Internet of Things: A Hybrid CNN–LSTM-Based Deep-Learning Approach
by Ali Vaziri, Pardis Sadatian Moghaddam, Mehrdad Shoeibi and Masoud Kaveh
Future Internet 2025, 17(4), 169; https://doi.org/10.3390/fi17040169 - 11 Apr 2025
Cited by 1 | Viewed by 797
Abstract
The Internet of Things (IoT) has revolutionized modern communication systems by enabling seamless connectivity among low-power devices. However, the increasing demand for high-performance wireless networks necessitates advanced frameworks that optimize both energy efficiency (EE) and security. Cell-free massive multiple-input multiple-output (CF m-MIMO) has [...] Read more.
The Internet of Things (IoT) has revolutionized modern communication systems by enabling seamless connectivity among low-power devices. However, the increasing demand for high-performance wireless networks necessitates advanced frameworks that optimize both energy efficiency (EE) and security. Cell-free massive multiple-input multiple-output (CF m-MIMO) has emerged as a promising solution for IoT networks, offering enhanced spectral efficiency, low-latency communication, and robust connectivity. Nevertheless, balancing EE and security in such systems remains a significant challenge due to the stringent power and computational constraints of IoT devices. This study employs secrecy energy efficiency (SEE) as a key performance metric to evaluate the trade-off between power consumption and secure communication efficiency. By jointly considering energy consumption and secrecy rate, our analysis provides a comprehensive assessment of security-aware energy efficiency in CF m-MIMO-based IoT networks. To enhance SEE, we introduce a hybrid deep-learning (DL) framework that integrates convolutional neural networks (CNN) and long short-term memory (LSTM) networks for joint EE and security optimization. The CNN extracts spatial features, while the LSTM captures temporal dependencies, enabling a more robust and adaptive modeling of dynamic IoT communication patterns. Additionally, a multi-objective improved biogeography-based optimization (MOIBBO) algorithm is utilized to optimize hyperparameters, ensuring an improved balance between convergence speed and model performance. Extensive simulation results demonstrate that the proposed MOIBBO-CNN–LSTM framework achieves superior SEE performance compared to benchmark schemes. Specifically, MOIBBO-CNN–LSTM attains an SEE gain of up to 38% compared to LSTM and 22% over CNN while converging significantly faster at early training epochs. Furthermore, our results reveal that SEE improves with increasing AP transmit power up to a saturation point (approximately 9.5 Mb/J at PAPmax=500 mW), beyond which excessive power consumption limits efficiency gains. Additionally, SEE decreases as the number of APs increases, underscoring the need for adaptive AP selection strategies to mitigate static power consumption in backhaul links. These findings confirm that MOIBBO-CNN–LSTM offers an effective solution for optimizing SEE in CF m-MIMO-based IoT networks, paving the way for more energy-efficient and secure IoT communications. Full article
(This article belongs to the Special Issue Moving Towards 6G Wireless Technologies—2nd Edition)
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14 pages, 2777 KiB  
Article
Optimizing Fermentation of Morus nigra L. Residues with Schizophyllum commune to Enhance Anthocyanin Release and Anti-Inflammatory Activity via Pyroptosis Pathway Modulation
by Lin Ye, Qin Hu, Ying Lin and Chaowan Guo
Fermentation 2025, 11(3), 145; https://doi.org/10.3390/fermentation11030145 - 14 Mar 2025
Viewed by 660
Abstract
Morus nigra L. is rich in anthocyanins and other active ingredients, but its extraction residues pose a burden on the environment. In the present study, Morus nigra L. extraction residue resource utilization was achieved through liquid fermentation of Schizophyllum commune, with the aim [...] Read more.
Morus nigra L. is rich in anthocyanins and other active ingredients, but its extraction residues pose a burden on the environment. In the present study, Morus nigra L. extraction residue resource utilization was achieved through liquid fermentation of Schizophyllum commune, with the aim of enhancing anthocyanin solubilization and evaluating anti-inflammatory activity. Response surface methodology was used to optimize fermentation parameters and quantify anthocyanin fractions by HPLC. The anti-inflammatory effect was evaluated using the lipopolysaccharide-induced inflammation model of human foreskin fibroblast (BJ cell), and the interaction of cyanidin-3-O-glucoside (C3G) with NLRP3, a key target of the pyroptosis pathway, was resolved by molecular docking. Our results indicated that the optimal conditions (substrate 3.4%, inoculum 9%, time 50 h) enabled the total anthocyanin to reach 85.1 μg/mL, of which the C3G content was elevated to 66.7 μg/mL (release efficiency of 83.9%). The fermented filtrate effectively promoted BJ cell proliferation and inhibited the lipopolysaccharide-induced inflammatory response, with the pyroptosis signaling pathway playing a significant role. Molecular docking confirmed that C3G binds strongly to the NLRP3 protein. This technology provides a new strategy for high-value utilization of Morus nigra L. residues and the development of natural anti-inflammatory drugs. Full article
(This article belongs to the Section Industrial Fermentation)
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14 pages, 2223 KiB  
Article
Metal Ion Reduction, Chelation, and Cytotoxicity of Selected Bicyclic Monoterpenes and Their Binary Mixtures
by Karolina Wojtunik-Kulesza, Marcela Dubiel and Katarzyna Klimek
Metabolites 2025, 15(3), 199; https://doi.org/10.3390/metabo15030199 - 13 Mar 2025
Cited by 1 | Viewed by 629
Abstract
Background/Objectives: Bicyclic monoterpenes are one of the most common groups of secondary plant metabolites found in Nature. Their wide spectrum of biological activity can be used in the prevention and in the treatment of various diseases, including so-called ‘diseases of civilization’. Their [...] Read more.
Background/Objectives: Bicyclic monoterpenes are one of the most common groups of secondary plant metabolites found in Nature. Their wide spectrum of biological activity can be used in the prevention and in the treatment of various diseases, including so-called ‘diseases of civilization’. Their potential for synergistic interactions may influence the biological activities of more complex mixtures. Methods: This study investigated the ability of selected bicyclic monoterpenes and their binary mixtures to reduce Fe(III) and Cu(II) and chelate Fe(II) and assessed their cytotoxic activity against BJ and HepG2 cell lines. Results: The obtained results did not reveal synergistic interactions towards the biological activities, but binary mixtures proved to be safe in relation to the tested cell lines. Among the tested single monoterpenes, the most effective were 3-carene and β-pinene, with the latter exhibiting the greatest ability to decrease cell viability (CC50 for BJ and HepG2 cells was about 1.08 and 1.85 mM, respectively). Conclusions: The results revealed that both single compounds and binary mixtures demonstrate the ability to reduce selected metal ions and chelate Fe(II) ions. Synergistic interactions were not observed, but an increase in the activity of selected binary mixtures was recorded. Based on cell culture experiments, the monoterpenes and their binary mixtures can be considered safe at a concentration lower than 1 mM and close to 0.313 mM, respectively. Full article
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18 pages, 2142 KiB  
Article
Towards DFO*12—Preliminary Results of a New Chelator for the Complexation of Actinium-225
by Irene V. J. Feiner, Dennis Svatunek, Martin Pressler, Tori Demuth, Xabier Guarrochena, Johannes H. Sterba, Susanne Dorudi, Clemens Pichler, Christoph Denk and Thomas L. Mindt
Pharmaceutics 2025, 17(3), 320; https://doi.org/10.3390/pharmaceutics17030320 - 1 Mar 2025
Viewed by 1409
Abstract
Background: Actinium-225 (225Ac) has gained interest in nuclear medicine for use in targeted alpha therapy (TAT) for the treatment of cancer. However, the number of suitable chelators for the stable complexation of 225Ac3+ is limited. The promising physical [...] Read more.
Background: Actinium-225 (225Ac) has gained interest in nuclear medicine for use in targeted alpha therapy (TAT) for the treatment of cancer. However, the number of suitable chelators for the stable complexation of 225Ac3+ is limited. The promising physical properties of 225Ac result in an increased demand for the radioisotope that is not matched by its current supply. To expand the possibilities for the development of 225Ac-based TAT therapeutics, a new hydroxamate-based chelator, DFO*12, is described. We report the DFT-guided design of dodecadentate DFO*12 and an efficient and convenient automated solid-phase synthesis for its preparation. To address the limited availability of 225Ac, a small-scale 229Th/225Ac generator was constructed in-house to provide [225Ac]AcCl3 for research. Methods: DFT calculations were performed in ORCA 5.0.1 using the BP86 functional with empirical dispersion correction D3 and Becke–Johnson damping (D3BJ). The monomer synthesis over three steps enabled the solid-phase synthesis of DFO*12. The small-scale 229Th/225Ac generator was realized by extracting 229Th from aged 233U material. Radiolabeling of DFO*12 with 225Ac was performed in 1 M TRIS pH 8.5 or 1.5 M NaOAc pH 4.5 for 30 min at 37 °C. Results: DFT calculations directed the design of a dodecadentate chelator. The automated synthesis of the chelator DFO*12 and the development of a small-scale 229Th/225Ac generator allowed for the radiolabeling of DFO*12 with 225Ac quantitatively at 37 °C within 30 min. The complex [225Ac]Ac-DFO*12 indicated good stability in different media for 20 h. Conclusions: The novel hydroxamate-based dodecadentate chelator DFO*12, together with the developed 229Th/225Ac generator, provide new opportunities for 225Ac research for future radiopharmaceutical development and applications in TAT. Full article
(This article belongs to the Special Issue Advances in Radiopharmaceuticals for Disease Diagnoses and Therapy)
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19 pages, 7288 KiB  
Article
Sparstolonin B Suppresses Proliferation and Modulates Toll-like Receptor Signaling and Inflammatory Pathways in Human Colorectal Cancer Cells
by Bürke Çırçırlı, Çağatay Yılmaz, Tuğçe Çeker, Zerrin Barut, Esma Kırımlıoğlu and Mutay Aslan
Pharmaceuticals 2025, 18(3), 300; https://doi.org/10.3390/ph18030300 - 21 Feb 2025
Viewed by 799
Abstract
Background: Sparstolonin B (SsnB), a natural compound with anti-inflammatory and anti-proliferative properties, was investigated for its effects on cell viability, apoptosis, and inflammatory pathways in human colorectal cancer cells (HCT-116) and healthy human fibroblasts (BJ). Phorbol 12-myristate 13-acetate (PMA), a tumor promoter and [...] Read more.
Background: Sparstolonin B (SsnB), a natural compound with anti-inflammatory and anti-proliferative properties, was investigated for its effects on cell viability, apoptosis, and inflammatory pathways in human colorectal cancer cells (HCT-116) and healthy human fibroblasts (BJ). Phorbol 12-myristate 13-acetate (PMA), a tumor promoter and inflammatory activator, was used to stimulate proliferation and inflammatory pathways. Methods: HCT-116 and BJ cells were treated with SsnB (3.125–50 μM) or PMA (1–10 nM) for 12–18 h. Cell viability was assessed using MTT analysis, while apoptosis was evaluated through cleaved caspase-3 staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry. Proliferation was analyzed through proliferating cell nuclear antigen (PCNA) staining. Toll-like receptor (TLR) signaling, cytokine expression, and sphingolipid levels were measured using immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and mass spectrometry, respectively. Results: SsnB reduced HCT-116 cell viability in a dose- and time-dependent manner with minimal effects on BJ cells. SsnB (25 μM, 12 h) decreased HCT-116 viability 0.6-fold, while PMA (10 nM, 12 h) increased it 2-fold (p < 0.01). No significant change was observed in BJ cells. PCNA fluorescence staining increased 2-fold with PMA and decreased 0.4-fold with SsnB (p < 0.001). PMA upregulated TLR2 and TLR4 mRNA and protein levels, with MyD88, p-ERK, and pNF-κB fluorescence increasing 2.1-, 1.5-, and 1.7-fold, respectively (p < 0.001). PMA elevated TNF-α, IL-1β, and IL-6 levels (p < 0.01). SsnB suppressed PMA-induced effects and promoted apoptosis, increasing cleaved caspase-3 levels by 1.5-fold and TUNEL staining by 1.9-fold (p < 0.01). Flow cytometry confirmed a significant increase in early and late apoptotic cells in the SsnB group. SsnB also increased ceramide (C18, C20, C22, and C24) levels (1.3- to 2.5-fold, p < 0.01) while reducing PMA-induced S1P and C1P increases (p < 0.01). Conclusions: SsnB selectively inhibits proliferation, induces apoptosis, and modulates inflammatory and sphingolipid pathways in colorectal cancer cells, with minimal toxicity to healthy fibroblasts, supporting its potential as a targeted therapeutic agent. Full article
(This article belongs to the Section Natural Products)
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17 pages, 4729 KiB  
Article
Discovery of MK8383s with Antifungal Activity from Mangrove Endophytic Fungi Medicopsis sp. SCSIO 40440 Against Fusarium Wilt of Banana
by Tianyu Zhou, Yulei Qiao, Lu Wang, Zifeng Li, Haibo Zhang, Liping Zhang, Shengrong Liao, Minhui Li, Changsheng Zhang and Wenjun Zhang
Mar. Drugs 2025, 23(2), 88; https://doi.org/10.3390/md23020088 - 18 Feb 2025
Viewed by 813
Abstract
Fusarium wilt of banana (FWB), caused by Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 (TR4), poses a severe threat to the global banana industry. The screening of endophytic fungi from the mangrove plant led to the identification of Medicopsis sp. [...] Read more.
Fusarium wilt of banana (FWB), caused by Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 (TR4), poses a severe threat to the global banana industry. The screening of endophytic fungi from the mangrove plant led to the identification of Medicopsis sp. SCSIO 40440, which exhibited potent antifungal activity against Fusarium. The further fraction of the extract yielded ten compounds, including MK8383 (1) and nine new analogues, MK8383s B-J (210). The structures of 110 were elucidated using extensive spectroscopic data and single-crystal X-ray diffraction analysis. In vitro antifungal assays revealed that 1 showed strongly antifungal activities against Foc TR4, with an EC50 of 0.28 μg/mL, surpassing nystatin and hygromycin B (32 and 16 μg/mL, respectively). Pot experiments showed that 1 or spores of SCSIO 40440 could significantly reduce the virulence of Foc TR4 on Cavendish banana. Full article
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14 pages, 7012 KiB  
Article
The Effect of A-Cation and X-Anion Substitutions on the Electronic and Structural Properties of A2ZrX6 ‘Defect’ Perovskite Materials: A Theoretical Density Functional Theory Study
by Christina Kolokytha, Nektarios N. Lathiotakis, Andreas Kaltzoglou, Ioannis D. Petsalakis and Demeter Tzeli
Materials 2025, 18(3), 726; https://doi.org/10.3390/ma18030726 - 6 Feb 2025
Viewed by 914
Abstract
In the present work, nine ‘defect’ perovskites with the chemical formula A2ZrX6 have been studied, where the A-site cations are a methylammonium cation, formamidinium cation, and trimethyl-sulfonium cation and the X-site anions are halogen, X = Cl, Br, and I. [...] Read more.
In the present work, nine ‘defect’ perovskites with the chemical formula A2ZrX6 have been studied, where the A-site cations are a methylammonium cation, formamidinium cation, and trimethyl-sulfonium cation and the X-site anions are halogen, X = Cl, Br, and I. We employ periodic DFT calculations using GGA-PBE, MBJ, HSEsol, and HSE06 functionals. All studied compounds exhibit a wide-bandgap energy that ranges from 5.22 eV to 2.11 eV, while for some cases, geometry optimization led to significant structural modification. It was found that the increase in the halogen size resulted in a decrease in the bandgap energy. The choice of the organic A-site cation affects the bandgap as well, which is minimal for the methylammonium cation. Such semiconductors with organic cations may be utilized in optoelectronic devices, given the substantial benefit of solution processability and thin film formation compared to purely inorganic analogs, such as Cs2ZrX6. Full article
(This article belongs to the Section Advanced Nanomaterials and Nanotechnology)
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