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33 pages, 3122 KB  
Review
Thermal Side-Channel Threats in Densely Integrated Microarchitectures: A Comprehensive Review for Cyber–Physical System Security
by Amrou Zyad Benelhaouare, Idir Mellal, Michel Saydé, Gabriela Nicolescu and Ahmed Lakhssassi
Micromachines 2025, 16(10), 1152; https://doi.org/10.3390/mi16101152 (registering DOI) - 11 Oct 2025
Abstract
Densely integrated microarchitectures spanning three-dimensional integrated circuits (3D-ICs), chiplet-based designs, and system-in-package (SiP) assemblies make heat a first-order security concern rather than a mere reliability issue. This review consolidates the landscape of thermal side-channel attacks (TSCAs) on densely integrated microarchitectures: we systematize observation [...] Read more.
Densely integrated microarchitectures spanning three-dimensional integrated circuits (3D-ICs), chiplet-based designs, and system-in-package (SiP) assemblies make heat a first-order security concern rather than a mere reliability issue. This review consolidates the landscape of thermal side-channel attacks (TSCAs) on densely integrated microarchitectures: we systematize observation vectors and threat models, clarify core concepts and assumptions, compare the most credible evidence from the past decade, and distill the main classes of defenses across the hardware–software stack. We also explain why hardening against thermal leakage is integral to cyber–physical system (CPS) security and outline the most promising research directions for the field. The strategic relevance of this agenda is reflected in current policy and funding momentum, including initiatives by the United States Department of Homeland Security and the Cybersecurity and Infrastructure Security Agency (DHS/CISA) on operational technology (OT) security, programs by the National Science Foundation (NSF) on CPS, and Canada’s Regional Artificial Intelligence Initiative and Cyber-Physical Resilience Program (RAII, >CAD 35 million), to bridge advanced microelectronics with next-generation cybersecurity. This survey offers a clear, high-level map of the problem space and a focused baseline for future work. Full article
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22 pages, 5757 KB  
Article
The Multipartite Mitogenome of Camellia sinensis cv. Xinyang10 Reveals Frequent Reorganization and Hints at Phylogeographic History
by Ming-Hui Yan, Yan-Rong Du, Wei Tong, Jia-Meng Su, Guo-Qing Pu, Lu-Miao Yan, Tong-Tong Zhu and Wen-Wen Wang
Diversity 2025, 17(10), 705; https://doi.org/10.3390/d17100705 (registering DOI) - 11 Oct 2025
Abstract
Camellia sinensis cv. Xinyang10 is a nationally recognized elite tea cultivar selected from the Xinyang drought-resistant population, valued for its notable cold tolerance and broad adaptability. In this study, we present the first complete assembly and annotation of its mitogenome. The mitogenome features [...] Read more.
Camellia sinensis cv. Xinyang10 is a nationally recognized elite tea cultivar selected from the Xinyang drought-resistant population, valued for its notable cold tolerance and broad adaptability. In this study, we present the first complete assembly and annotation of its mitogenome. The mitogenome features a multipartite structure, consisting of a circular chromosome (798,917 bp) and a linear chromosome (46,159 bp), harboring a total of 74 genes. We identified extensive repetitive sequences (244 simple sequence repeats and 998 long sequence repeats), 211 RNA editing sites, and 16,614 bp of chloroplast-derived DNA, indicating a highly dynamic genome. Positive selection was detected in nad1 and ccmFC. Phylogenetic analysis based on mitochondrial SNP markers placed C. sinensis Xinyang10 closest to C. sinensis var. pubilimba. Notably, a phylogeny reconstructed based on mitogenomic collinearity displayed a distinct geographical pattern, supporting the hypothesized westward-to-eastward migration route of tea plants from southwestern China. These findings provide valuable genomic resources and demonstrate the utility of the mitogenome in understanding the evolutionary history of tea plants. Full article
(This article belongs to the Section Plant Diversity)
16 pages, 4097 KB  
Article
Experimental Study on the Rotary Adhesion of Shield Cutterhead Tunneling in Clay Strata at Different Temperatures
by Tao Zhang, Zhe Yuan, Jingchun Pang, Wenqiu Li and Zeen Wan
Buildings 2025, 15(20), 3657; https://doi.org/10.3390/buildings15203657 (registering DOI) - 11 Oct 2025
Abstract
In the process of shield tunneling in clayey strata, the fine-grained clay mineral components in the soil easily adhere to the cutter plate. The clay adhering to the cutterhead and the soil compartment then solidifies and hardens, which results in the production of [...] Read more.
In the process of shield tunneling in clayey strata, the fine-grained clay mineral components in the soil easily adhere to the cutter plate. The clay adhering to the cutterhead and the soil compartment then solidifies and hardens, which results in the production of mud cake and clogging. At present, research on cutter plates in clayey ground is limited and has focused mostly on static tests or simplified models. There is a lack of in-depth studies on the effect of temperature on clay adhesion, which is crucial for understanding the clogging risks. In this study, we independently researched and developed a rotary adhesion tester to investigate the adhesion effect and adhesion force change in a shield cutter plate under the influence of different temperatures, water contents (ω), and clay types, revealing the change rule of the adhesion effect under the joint influence of the temperature and the consistency index (Ic). This study provides experimental evidence and an empirical model for assessing the clogging risk in shield tunneling through clay strata, offering valuable insights that support the efficient operation of earth pressure balance (EPB) shields. Full article
(This article belongs to the Section Building Structures)
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17 pages, 1078 KB  
Article
Collagen Hydrolysate–Cranberry Mixture as a Functional Additive in Sausages
by Yasin Uzakov, Aziza Aitbayeva, Madina Kaldarbekova, Madina Kozhakhiyeva, Arsen Tortay and Kadyrzhan Makangali
Processes 2025, 13(10), 3233; https://doi.org/10.3390/pr13103233 - 10 Oct 2025
Abstract
Consumers increasingly seek clean-label meat products with improved nutrition and stability. We evaluated a collagen hydrolysate–cranberry mixture (CH-CR) as a functional additive in cooked sausages. Two formulations—control and CH-CR—were assessed for fatty acid profile; lipid and protein oxidation during storage; antioxidant capacity ferric-reducing [...] Read more.
Consumers increasingly seek clean-label meat products with improved nutrition and stability. We evaluated a collagen hydrolysate–cranberry mixture (CH-CR) as a functional additive in cooked sausages. Two formulations—control and CH-CR—were assessed for fatty acid profile; lipid and protein oxidation during storage; antioxidant capacity ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and half-maximal inhibitory concentration (IC50); amino acid composition; and instrumental color. Relative to the control, CH-CR produced a more favorable lipid profile: lower saturated fatty acids (SFAs) 23.9% vs. 28.0%, higher monounsaturated fatty acids (MUFAs) 53.2% vs. 49.3%, slightly higher polyunsaturated fatty acids (PUFAs) 23.3% vs. 22.7%, a higher PUFA/SFA ratio of 0.97 vs. 0.81, and a lower omega-6/omega-3 (n-6/n-3) ratio of 13.5 vs. 27.1, driven by higher alpha-linolenic acid (ALA) 1.6% vs. 0.8%, with trans fats <0.1%. Storage studies showed attenuated oxidation in CH-CR: lower peroxide value (PV) at day 10 8.1 ± 0.4 vs. 9.8 ± 0.5 meq/kg and lower thiobarbituric acid-reactive substances (TBARS) at day 6 0.042 ± 0.004 vs. 0.055 ± 0.006 mg MDA/kg and day 10 0.156 ± 0.016 vs. 0.590 ± 0.041 mg MDA/kg); the acid value at day 10 was similar. Antioxidant capacity increased with CH-CR FRAP 30.5 mg gallic acid equivalents (GAE)/g vs. not detected; DPPH inhibition was 29.88% vs. 10.23%; IC50 56.22 vs. 149.51 µg/mL. The amino acid profile reflected collagen incorporation—higher glycine+proline+hydroxyproline 2.37 vs. 1.38 g/100 g and a modest rise in indispensable amino acids (IAAs) 5.72 vs. 5.42 g/100 g, increasing the IAA/total amino acid (TAA) ratio to 0.411 vs. 0.380. CH-CR samples were lighter and retained redness better under light, with comparable overall color stability. Overall, CH-CR is a natural strategy to improve fatty acid quality and oxidative/color stability in sausages. Full article
(This article belongs to the Special Issue Food Processing and Ingredient Analysis)
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18 pages, 768 KB  
Article
What Influences the Public to Work as Crowdshippers Using Cargo Bikes? An Extended Theory of Planned Behavior
by Sunho Bang, Jiarong Chen, Kwangsup Shin and Woojung Kim
Systems 2025, 13(10), 895; https://doi.org/10.3390/systems13100895 - 10 Oct 2025
Abstract
Driven by the green and low-carbon transformation of urban logistics, the integration of crowdsourced delivery and green transportation is considered an important pathway to achieving sustainable last-mile delivery. This study focuses on urban crowdsourced delivery using cargo bikes and develops an extended behavioral [...] Read more.
Driven by the green and low-carbon transformation of urban logistics, the integration of crowdsourced delivery and green transportation is considered an important pathway to achieving sustainable last-mile delivery. This study focuses on urban crowdsourced delivery using cargo bikes and develops an extended behavioral model based on the Theory of Planned Behavior (TPB). The model systematically examines the key factors influencing the public’s behavioral intention (BI) to participate as crowdshippers. While retaining the core structure of TPB, the model incorporates external variables—perceived risk (PR), policy support (PS), and infrastructure conditions (IC)—to improve its explanatory power and applicability to real-world delivery scenarios. A questionnaire survey was conducted in South Korea, yielding 600 valid responses. The results indicate that usage attitude and perceived behavioral control exert significant positive effects on BI. PR has a significant negative effect on both attitude and BI. PS indirectly enhances BI by improving attitudes, whereas IC primarily influences BI by strengthening the public’s sense of control. This study not only expands the theoretical explanatory power of the TPB model in the context of green crowdsourced delivery but also provides empirical evidence for policymakers and platform operators. Full article
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19 pages, 1457 KB  
Article
Development and Evaluation of Hyaluronic Acid-Chitosan Coated Liposomes for Enhanced Delivery of Resveratrol to Breast Cancer Cells
by Yin Yin Myat, Khin Khin Gyi, Pornthida Riangjanapatee, Chuda Chittasupho, Songyot Anuchapreeda and Siriporn Okonogi
Polysaccharides 2025, 6(4), 93; https://doi.org/10.3390/polysaccharides6040093 - 10 Oct 2025
Abstract
Resveratrol (RES), a naturally occurring polyphenolic compound with well-documented anticancer potential, is limited in clinical application due to its poor aqueous solubility and low bioavailability. This study aimed to develop RES-loaded liposomes coated sequentially with chitosan (CS) and hyaluronic acid-chitosan (HA) (RES-HA-CS-Lip) to [...] Read more.
Resveratrol (RES), a naturally occurring polyphenolic compound with well-documented anticancer potential, is limited in clinical application due to its poor aqueous solubility and low bioavailability. This study aimed to develop RES-loaded liposomes coated sequentially with chitosan (CS) and hyaluronic acid-chitosan (HA) (RES-HA-CS-Lip) to enhance RES stability, delivery, and anticancer efficacy in breast cancer cells. HA-CS-coated liposomes were prepared using a thin-film hydration technique. Their physicochemical characteristics were thoroughly investigated through dynamic light scattering, transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The optimized RES-HA-CS-Lip exhibited spherical morphology with an average particle size of 212 nm, a narrow polydispersity index (<0.4), a zeta potential of +9.04 ± 1.0 mV, and high entrapment efficiency of 82.16%. Stability studies demonstrated superior retention of size, surface charge, and encapsulation efficiency over 28 days at both 4 °C and 25 °C. In vitro release profiles at physiological and acidic pH revealed sustained drug release, with enhanced release under acidic conditions mimicking the tumor microenvironment. Antioxidant activity, assessed via DPPH and ABTS radical-scavenging assays, indicated that RES retained its radical-scavenging potential upon encapsulation. Cytotoxicity assays demonstrated markedly improved anticancer activity against MCF-7 breast cancer cells, with an IC50 of 13.08 μg/mL at 48 h, while maintaining high biocompatibility toward normal HaCaT keratinocytes. RES-HA-CS-Lip demonstrated excellent stability against degradation and aggregation. Overall, these findings highlight HA-CS-coated liposomes as a promising polysaccharide-based nanocarrier that enhances stability, bioactivity, and therapeutic efficacy of RES, representing a potential strategy for targeted breast cancer therapy. Full article
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18 pages, 7157 KB  
Article
Perspective Back-Projection Algorithm: Interface Imaging for Airborne Ice Detection
by Yingge Wang, Jinbiao Zhu, Jie Pan and Yuquan Liu
Remote Sens. 2025, 17(20), 3400; https://doi.org/10.3390/rs17203400 - 10 Oct 2025
Abstract
The deployment of traditional ground-penetrating radar (GPR) systems for ice detection on steep terrain presents substantial safety challenges for ground crews due to inaccessibility and hazardous working conditions. However, airborne GPR (AGPR) and radio echo sounding (RES) provide solutions to these difficulties. Assuming [...] Read more.
The deployment of traditional ground-penetrating radar (GPR) systems for ice detection on steep terrain presents substantial safety challenges for ground crews due to inaccessibility and hazardous working conditions. However, airborne GPR (AGPR) and radio echo sounding (RES) provide solutions to these difficulties. Assuming that ice is homogeneous, we introduce a perspective back-projection algorithm designed to process AGPR or RES data that directly searches for unobstructed refracted electromagnetic (EM) wave paths and focuses EM energy below the surface by computing path-specific travel times. The results from the 2D and 3D imaging tests indicate that the perspective back-projection algorithm can accurately image the ice–rock interface. However, Snell’s Law suggests that part of the energy may fail to propagate through the air–ice interface and reach either the ice–rock interface or the receivers in scenarios where the incident angle of an EM wave exceeds a certain threshold. This energy deficit can hinder the perspective back-projection algorithm from accurately imaging such ice–rock interfaces. Despite these limitations, the perspective back-projection algorithm remains a promising tool for imaging sub-ice interfaces in AGPR and RES ice detection. Full article
(This article belongs to the Special Issue Electromagnetic Modeling of Geophysical Prospecting in Remote Sensing)
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18 pages, 1035 KB  
Article
Enzymatic Hydrolysis of Porcine Blood as a Strategy to Obtain a Peptide-Rich Functional Ingredient
by Cristina Moreno-Mariscal, Federico Moroni, Jaume Pérez-Sánchez, Leticia Mora and Fidel Toldrá
Int. J. Mol. Sci. 2025, 26(20), 9863; https://doi.org/10.3390/ijms26209863 - 10 Oct 2025
Abstract
The sustainable revalorization of porcine blood is crucial due to the large volumes daily generated in slaughterhouses. The aim of this study was to obtain a novel ingredient rich in free amino acids and bioactive peptides from the sequential hydrolysis of porcine blood. [...] Read more.
The sustainable revalorization of porcine blood is crucial due to the large volumes daily generated in slaughterhouses. The aim of this study was to obtain a novel ingredient rich in free amino acids and bioactive peptides from the sequential hydrolysis of porcine blood. Porcine blood was hydrolyzed with Alcalase 4.0 L and Protana™ Prime enzymes, followed by molecular weight fractionation (<10 kDa) and spray-drying. The antioxidant, hypoglycemic, and anti-inflammatory bioactivities of the resulting hydrolysate (PBSH) were studied in vitro. Further fractionation by reversed-phase high-performance liquid chromatography (RP-HPLC) was performed to isolate the most bioactive fraction based on polarity. Peptides from fraction 1 (F1) were identified using LC-MS/MS and analyzed in silico. Finally, some peptides were synthesized, and their bioactivity was subsequently assessed. PBSH hydrolysate showed antioxidant activity with IC50 values of 2.09, 135.05, and 26.73 mg/mL for ABTS, FRAP, and DPPH assays, respectively. Additionally, PBSH exhibited hypoglycemic, anti-inflammatory, and immunomodulatory potential through the inhibition of DPP-IV (82.78%), NEP (84.72%), TACE (50.79%), and MGL (69.08%) enzymes at a concentration of 20, 20, 100, and 20 mg/mL, respectively. Peptides PDDFNPS, FPPKPKD, DNPIPK, GHLDDLPG, and GDL were identified in the most polar and bioactive fraction (F1) and proved a synergistic hypoglycemic effect at a concentration of 1 mmol/L. The peptide PDDFNPS exhibited multifunctional properties with 56.43% inhibition of DPP-IV and 83.54% inhibition of NEP. PBSH resulted in a novel functional ingredient for animal feed as it contains a variety of identified bioactive peptides and a high amount of free amino acids. Full article
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22 pages, 9503 KB  
Article
Analysis of Annual Maximum Ice-Influenced and Open-Water Levels at Select Hydrometric Stations on Canadian Rivers
by Yonas Dibike, Laurent de Rham, Spyros Beltaos, Daniel L. Peters and Barrie Bonsal
Water 2025, 17(20), 2930; https://doi.org/10.3390/w17202930 - 10 Oct 2025
Abstract
River ice is a common feature in most Canadian rivers and streams during the cold season. River channel hydraulics under ice conditions may cause higher water levels at a relatively lower discharge compared to the open-water flood events. Elevated water levels resulting from [...] Read more.
River ice is a common feature in most Canadian rivers and streams during the cold season. River channel hydraulics under ice conditions may cause higher water levels at a relatively lower discharge compared to the open-water flood events. Elevated water levels resulting from river ice processes throughout fall freeze-over, mid-winter, and spring break-up are important hydrologic events with diverse morphological, ecological, and socio-economic impacts. This study analyzes the timing of maximum water levels (occurring during freeze-over, spring break-up, and open-water periods) and the typology of maximum ice-related events (at freeze-over, mid-winter, and spring break-up) using data from the Canadian River Ice Database. The study also compares annual maximum water levels during the river ice and open-water periods at selected hydrometric stations from 1966 to 2015, divided into two 25-year windows: 1966–1990 and 1991–2015. A return period classification method was applied to define ice-influenced, open-water, and mixed-regime conditions. The results indicate that the majority of ice-influenced maximum water levels occurred during spring break-up (~79% in 1966–1990 and ~69% in 1991–2015), followed by fall freeze-up (~13% and ~23%) and mid-winter break-up (~8% and ~7%) for the two periods, respectively. Among 15 stations analyzed for 1966–1990 and 42 stations for 1991–2015, the proportion of annual maximum water levels dominated by open-water conditions increased from 47% to 55%, while ice-dominated events decreased from 13% to 12%, and mixed-regime events dropped from 40% to 33%. However, a focused comparison of eight common stations revealed minimal change in the distribution of water level-generating events between the two periods. The findings offer valuable insights into the spatial distribution of maximum water level-generating mechanisms across Canada. Full article
(This article belongs to the Special Issue Hydroclimatic Changes in the Cold Regions)
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28 pages, 4508 KB  
Article
Enhanced Killing of Colon Cancer Cells by Mesoporous Silica Nanoparticles Loaded with Ellagic Acid
by Khaled AbouAitah, Amr Nassrallah, Ahmed A. F. Soliman, Anna Swiderska-Sroda, Tadeusz Chudoba, Julita Smalc-Koziorowska, Beom Soo Kim and Witold Łojkowski
Nanomaterials 2025, 15(20), 1547; https://doi.org/10.3390/nano15201547 (registering DOI) - 10 Oct 2025
Abstract
Background: Natural compounds, including ellagic acid (ELG), are promising anticancer agents with low adverse effects. In this paper, we test in vitro the effectiveness of mesoporous silica nanoparticles (MSN) as an ELG carrier against colon cancer. Methods: We produced MSNs functionalized with triptycene [...] Read more.
Background: Natural compounds, including ellagic acid (ELG), are promising anticancer agents with low adverse effects. In this paper, we test in vitro the effectiveness of mesoporous silica nanoparticles (MSN) as an ELG carrier against colon cancer. Methods: We produced MSNs functionalized with triptycene (TRP) and loaded with ELG, further called MSNTRPELG nanoformulation. The nanoformulation contained over 11 wt.% TRP and approximately 25 wt.% ELG in the mesoporous structure and on the surface of particles. It was assessed for anticancer effects against two colon cancer cells: HCT-116 and HT-29 for treatment with up to 200 µM. Results: Comparing to free ELG, we have shown a three times higher cancer inhibition. The lowest IC50 values were for HCT-116 (88.1 ± 0.1 µM) and HT-29 (77.6 ± 0.1 µM). When treated with free ELG, the values were 187.1 ± 0.1 µM and 300.0 ± 0.1 µM, respectively. MSNTRPELG enhanced apoptosis primarily by activating caspase-3, p53, and Bax while downregulating Bcl-2 in HCT-116 and HT-29 cells. It also inhibited receptor tyrosine kinases (HER2 and VEGFR2). Preliminary Western blot observations suggest suppression of B-RAF, C-RAF, and K-RAS oncogenes, with stronger inhibition by the nanoformulation than by free ELG. Conclusions: This work highlights the potential of MSNs to enhance the efficacy of natural prodrugs, particularly ELG, in cancer therapy. Full article
(This article belongs to the Special Issue Metal Nanostructures in Biological Applications)
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24 pages, 1693 KB  
Article
Lead Structure-Based Hybridization Strategy Reveals Major Potency Enhancement of SirReal-Type Sirt2 Inhibitors
by Matthias Frei, Ricky Wirawan, Thomas Wein and Franz Bracher
Int. J. Mol. Sci. 2025, 26(20), 9855; https://doi.org/10.3390/ijms26209855 - 10 Oct 2025
Abstract
Selective and potent inhibitors of the NAD+-dependent deacetylase Sirt2 represent a valuable epigenetic strategy for the treatment of currently incurable diseases such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis. Guided by molecular docking and MM/GBSA validation studies, a [...] Read more.
Selective and potent inhibitors of the NAD+-dependent deacetylase Sirt2 represent a valuable epigenetic strategy for the treatment of currently incurable diseases such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis. Guided by molecular docking and MM/GBSA validation studies, a lead structure-based hybridization strategy was developed, resulting in a series of very effective Sirt2 inhibitors. With RW-93, we present a highly potent and subtype selective Sirt2 inhibitor (IC50 = 16 nM), which as a next generation SirReal-type inhibitor significantly surpasses established Sirt2 inhibitors and contributes to the extension of the current SAR profile. The structural modification strategy employed in this study proved to be highly promising, resulting in the identification of the most potent low-molecular-weight Sirt2 inhibitor reported to date, providing a promising target for further medicinal chemistry-driven SAR studies. Full article
(This article belongs to the Section Molecular Biology)
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17 pages, 4552 KB  
Article
Antiviral Efficacy of Lignan Derivatives (-)-Asarinin and Sesamin Against Foot-and-Mouth Disease Virus by Targeting RNA-Dependent RNA Polymerase (3Dpol)
by Ploypailin Semkum, Natjira Mana, Varanya Lueangaramkul, Nantawan Phetcharat, Porntippa Lekcharoensuk and Sirin Theerawatanasirikul
Vet. Sci. 2025, 12(10), 971; https://doi.org/10.3390/vetsci12100971 - 10 Oct 2025
Abstract
Foot-and-mouth disease (FMD) is a highly contagious viral infection affecting livestock. Although inactivated vaccines are commonly used, their effectiveness is limited by an immunity gap. Therefore, complementary antiviral strategies are required for effective control and prevention. Lignans, plant-derived compounds, have shown promising antiviral [...] Read more.
Foot-and-mouth disease (FMD) is a highly contagious viral infection affecting livestock. Although inactivated vaccines are commonly used, their effectiveness is limited by an immunity gap. Therefore, complementary antiviral strategies are required for effective control and prevention. Lignans, plant-derived compounds, have shown promising antiviral properties, yet their potential against foot-and-mouth disease virus (FMDV) remains underexplored. This study employed virtual screening to identify lignan compounds targeting viral RNA-dependent RNA polymerase (3Dpol). Six lignan compounds were selected for cytotoxicity and antiviral activity evaluation including pre-viral entry, post-viral entry, and protective effect assays. Antiviral activity assay showed that (-)-asarinin and sesamin exhibit potent inhibition effects in the post-viral entry with EC50 of 15.11 μM and 52.98 μM, respectively, using immunoperoxidase monolayer assay. Both compounds exhibited dose-dependent reduction in viral replication with significant suppression of negative-strand RNA production. Lignans’ ability to target FMDV 3Dpol was further confirmed using a cell-based FMDV minigenome assay. Among the tested lignans, (-)-asarinin demonstrated remarkable inhibition of GFP expression (IC50 value at 10.37 μM), while sesamin required a higher concentration for similar effects. In silico prediction revealed that these lignans preferentially bind to FMDV 3Dpol active site. These findings are the first to establish (-)-asarinin and sesamin as promising antiviral candidates against FMDV. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
20 pages, 3833 KB  
Article
Targeting NFAT2 for Reversing the P-gp-Mediated Multidrug Resistance to Paclitaxel by Manidipine
by Jian Zhou, Nan Wang, Yu-Kang Lin, Qi-Lu Li, Rui-Ming Liu, Jia-Qin Hu, Hua Zhou, Hai Lan and Ying Xie
Cancers 2025, 17(20), 3289; https://doi.org/10.3390/cancers17203289 - 10 Oct 2025
Abstract
Background: Multidrug resistance (MDR), primarily driven by P-glycoprotein (P-gp)-mediated drug efflux, presents a significant challenge in cancer therapy, contributing to chemotherapy failure and poor patient outcomes. Objectives: In this study, we explored the potential of manidipine (MA), a clinically approved calcium channel blocker, [...] Read more.
Background: Multidrug resistance (MDR), primarily driven by P-glycoprotein (P-gp)-mediated drug efflux, presents a significant challenge in cancer therapy, contributing to chemotherapy failure and poor patient outcomes. Objectives: In this study, we explored the potential of manidipine (MA), a clinically approved calcium channel blocker, to reverse P-gp-mediated MDR through modulation of calcium signaling via nuclear factor of activated T cells 2 (NFAT2). Methods: Paclitaxel (PTX) resistance ABCB1-overexpressing cancer in vitro and in vivo were used for evualting the anti-MDR effects of MA, as well as the underlying mechanism with siRNA of NFAT2. Results: We found that MA at non-toxic concentrations (0.6–5.4 μM) significantly sensitize drug-resistant colorectal (HCT-8/T) and non-small cell lung (A549/T) cells to PTX, reducing its IC50 by up to 1328-fold in vitro models. Mechanistically, MA inhibited P-gp efflux activity without altering its expression, as shown by an increased intracellular accumulation of doxorubicin and Flutax-2 (2.3- and 3.1-fold, respectively) and dose-dependent modulation of ATPase activity (EC50 = 4.16 μM). Notably, MA reduced intracellular calcium levels (52% reduction, p < 0.001) and downregulated NFAT2, an oncogene overexpressed in resistant cells. In vivo, MA (3.5 mg/kg) synergizes with PTX to inhibit tumor growth by 68% (p < 0.001) in A549/T xenograft model, without an observable decrease in weight. Conclusions: In sum, all these results position MA as a novel NFAT2 inhibitor to overcome P-gp-mediated MDR via modulating calcium signaling, which points to further investigation for its clinical applications. Full article
(This article belongs to the Section Molecular Cancer Biology)
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25 pages, 2645 KB  
Article
Physicochemical and Functional Characterization of Pearl Millet-Based Probiotic Beverage for Antiaging Potential in Caenorhabditis elegans
by Nova Henna Jemimah Kaila, Prakash M. Halami, Chethana Ramakrishna, Mamatha Singanahalli Shivaramu and Muthukumar Serva Peddha
Foods 2025, 14(20), 3460; https://doi.org/10.3390/foods14203460 (registering DOI) - 10 Oct 2025
Abstract
Probiotics like Lactobacillus sp. are extensively studied for their beneficial host interactions, including the gut–brain axis, anti-inflammatory effects, immune system interactions, restoration of gut dysbiosis, and anti-aging effects. In the current study, pearl millet was fermented with Lactobacillus plantarum strains DHCU 70 and [...] Read more.
Probiotics like Lactobacillus sp. are extensively studied for their beneficial host interactions, including the gut–brain axis, anti-inflammatory effects, immune system interactions, restoration of gut dysbiosis, and anti-aging effects. In the current study, pearl millet was fermented with Lactobacillus plantarum strains DHCU 70 and MCC 5231, which enhanced the nutritional, bioactive, and functional properties of derived probiotic beverages. Compared to unfermented controls, fermented beverages exhibited increased protein content and vitamins B1, B2, and B3, with decreased carbohydrate and dietary fiber levels. The probiotics have maintained viability exceeding 12 log CFU/mL and showed resistance to harsh gastrointestinal conditions. Fermentation increased total phenolic content from 13.38 ± 0.40 mg GAE/100 g to 42.10 ± 2.65 mg GAE/100 g (LPDB) and 47.76 ± 1.37 mg GAE/100 g (LPMB) and total flavonoid content from 13.01 ± 1.18 mg QE/100 g to 23.12 ± 2.73 mg QE/100 g and 24.21 ± 0.98 mg QE/100 g, respectively. Antioxidant assays showed DPPH radical scavenging improved by 37%, ferrous ion chelation rose from 71.69 ± 0.09 mg TE/100 g to 91.45 ± 0.006 mg TE/100 g, ABTS scavenging increased from 71.62 mg TE/100 g to 82.51 ± 0.04 mg TE/100 g (LPDB) and 89.74 ± 0.04 mg TE/100 g (LPMB) and superoxide radical inhibition rose from 51.40 ± 0.98% to 81.77 ± 0.03% (LPDB) and 79.92 ± 0.02% (LPMB). In the in vivo model, Caenorhabditis elegans, fermented beverage treatments significantly improved health-span parameters like head-swing frequency (13.51% increase), body bend frequency (8.41% increase), pharyngeal pumping (8.15% increase) with reduced lipofuscin accumulation and intracellular reactive oxygen species while median lifespan extended beyond 24 days versus 14–16 days in controls (p < 0.05). Gompertz mortality modeling revealed a significant decrease in the aging rate parameter, indicating systemic mitigation of stress-induced physiological decline. These combined nutritional, bioactive, and in vivo longevity results underscore the potential of L. plantarum-fermented pearl millet beverages as functional nutraceuticals that target oxidative stress and promote healthy aging. Full article
(This article belongs to the Section Drinks and Liquid Nutrition)
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Article
Ozone-Assisted Green Upgrading of Lactuca sativa Oil: Characterization and Bioactivity for Clean-Label Functional Applications
by Abdulrahman S. Bazaid, Sulaiman A. Alsalamah, Waleed Hakami, Mohammed Ibrahim Alghonaim, Amro Duhduh and Husam Qanash
Foods 2025, 14(20), 3458; https://doi.org/10.3390/foods14203458 - 10 Oct 2025
Abstract
Ozonation is an emergent green technology that modifies the chemical composition and bioactivity of natural oils, creating new opportunities for functional and biomedical use. In this study, the chemical changes and in vitro activities of lettuce (Lactuca sativa) oil before and [...] Read more.
Ozonation is an emergent green technology that modifies the chemical composition and bioactivity of natural oils, creating new opportunities for functional and biomedical use. In this study, the chemical changes and in vitro activities of lettuce (Lactuca sativa) oil before and after ozonation were evaluated. Gas chromatography–mass spectrometry (GC–MS) revealed an increase in both the number and diversity of constituents in ozonated oil, with (Z)-13-docosenamide and trans-13-octadecenoic acid as predominant components. Fourier-transform infrared (FTIR) spectra showed overall similarity between native and ozonated oils, but with three additional characteristic bands in the ozonated sample. Bioassays demonstrated that ozonation enhanced anti-Helicobacter pylori activity (inhibition zone 21.3 ± 0.3 mm), supported bactericidal effects, and improved antibiofilm and antihemolytic properties. The antioxidant capacity of ozonated oil was modestly increased (IC50 = 3.95 ± 0.4 µg/mL), while butyrylcholinesterase inhibition was more markedly enhanced (IC50 = 2.58 ± 0.6 µg/mL), compared to that of the non-ozonated oil (IC50 = 6.14 ± 0.3 µg/mL and IC50 = 4.38 ± 0.4 µg/mL, respectively). Molecular docking suggested strong interactions of major ozonation-derived compounds with human BuChE and H. pylori urease, providing mechanistic support for the observed activities. Overall, these results indicate that ozonation modestly but consistently enhances the biological potential of lettuce oil through compositional shifts, highlighting its promise for development as a safe functional food ingredient with possible biomedical applications. Full article
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