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Keywords = delayed product inhibition

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15 pages, 7983 KB  
Article
Antifungal Activity of Acorus calamus Essential Oil Against Rice Blast Fungus Magnaporthe oryzae and Its Composition Characterization
by Shuzhen Deng, Ziyi Wang, Yusi Li, Yiming Liu, Zhiyi Kong, Ge Meng, Saige Jin, Anqi Zeng, Huan Liu and Shengming Liu
Plants 2026, 15(2), 332; https://doi.org/10.3390/plants15020332 - 22 Jan 2026
Viewed by 43
Abstract
Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most devastating diseases affecting global rice production. Plant essential oils (EOs) have been considered as a promising green alternative to synthetic fungicides. In this study, the antifungal activities of [...] Read more.
Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most devastating diseases affecting global rice production. Plant essential oils (EOs) have been considered as a promising green alternative to synthetic fungicides. In this study, the antifungal activities of five plant EOs—Acorus calamus, Citrus reticulata, Syzygium aromaticum, Paeonia suffruticosa, and Melaleuca viridiflora—against M. oryzae were evaluated using the mycelial growth rate method. Among them, A. calamus EO (ACEO) exhibited the most pronounced inhibitory effect, with an EC50 value of 0.37 μL/mL. It significantly delayed or inhibited conidial germination and appressorium formation. At higher concentrations (≥1 μL/mL), it also caused morphological abnormalities in appressoria. Observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that the EO treatment caused hyphal surface wrinkling, cell wall thinning, organelle dissolution, and vacuolation. Pathogenicity tests further confirmed that ACEO reduced the virulence of the fungus remarkably, with nearly complete loss of pathogenicity at a concentration of 1 μL/mL. Finally, ACEO was analyzed using gas chromatography-mass spectrometry (GC-MS). The most abundant constituents identified were β-asarone (19.83%) and isoshyobunone (14.92%). Together, these findings demonstrate that ACEO impairs fungal pathogenicity by disrupting hyphal morphology and cellular integrity, highlighting its potential as an effective and eco-friendly fungicide for controlling rice blast. Full article
(This article belongs to the Section Plant Protection and Biotic Interactions)
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16 pages, 1597 KB  
Article
Thermal and Fat Organic Loading Effects on Anaerobic Digestion of Dairy Effluents
by Juana Fernández-Rodríguez, Montserrat Pérez and Diana Francisco
Biomass 2026, 6(1), 8; https://doi.org/10.3390/biomass6010008 - 9 Jan 2026
Viewed by 183
Abstract
The untreated discharge of dairy industry wastewater, characterized by high organic and nutrient loads, poses a severe eutrophication threat, leading to oxygen depletion and the disruption of aquatic ecosystems, which necessitates advanced treatment strategies. Anaerobic digestion (AD) represents an effective and sustainable alternative, [...] Read more.
The untreated discharge of dairy industry wastewater, characterized by high organic and nutrient loads, poses a severe eutrophication threat, leading to oxygen depletion and the disruption of aquatic ecosystems, which necessitates advanced treatment strategies. Anaerobic digestion (AD) represents an effective and sustainable alternative, converting organic matter into biogas while minimizing sludge production and contributing to Circular Economy strategies. This study investigated the effects of fat concentration and operational temperature on the anaerobic digestion of dairy effluents. Three types of effluents, skimmed, semi-skimmed, and whole substrates, were evaluated under mesophilic 35 °C and thermophilic 55 °C conditions to degrade substrates with different fat content. Low-fat effluents exhibited higher COD removal, shorter lag phases, and stable activity under mesophilic conditions, while high-fat substrates delayed start-up due to accumulation of fatty acids and brief methanogen inhibition. Thermophilic digestion accelerated hydrolysis and methane production but demonstrated increased sensitivity to lipid-induced inhibition. Kinetic modeling confirmed that the modified Gompertz model accurately described mesophilic digestion with rapid microbial adaptation, while the Cone model better captured thermophilic, hydrolysis-limited kinetics. The thermophilic operation significantly enhanced methane productivity, yielding 105–191 mL CH4 g−1VS compared to 54–70 mL CH4 g−1VS under mesophilic conditions by increasing apparent hydrolysis rates and reducing lag phases. However, the mesophilic process demonstrated superior operational stability and robustness during start-up with fat-rich effluents, which otherwise suffered delayed methane formation due to lipid hydrolysis and volatile fatty acid (VFA) inhibition. Overall, the synergistic interaction between temperature and fat concentration revealed a trade-off between methane productivity and process stability, with thermophilic digestion increasing methane yields up to 191 mL CH4 g−1 VS but reducing COD removal and robustness during start-up, whereas mesophilic operation ensured more stable performance despite lower methane yields. Full article
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23 pages, 4877 KB  
Article
Durability and Microstructural Evolution of PVA-Fiber-Reinforced Concrete Under Coupled Sulfate Attack and Freeze–Thaw Conditions
by Hairong Wu, Changhao Shen, Chenjie Lv, Yuzhou Sun, Songzhao Qu and Xiangming Zhou
Materials 2026, 19(1), 98; https://doi.org/10.3390/ma19010098 - 27 Dec 2025
Viewed by 388
Abstract
To address the engineering challenge of durability deterioration in concrete structures in the cold and saline regions in northern China, this study investigated PVA fiber-reinforced concrete under combined sulfate attack and freeze–thaw cycles using PVA fiber volume fractions (0%, 0.1%, 0.3%, 0.5%) and [...] Read more.
To address the engineering challenge of durability deterioration in concrete structures in the cold and saline regions in northern China, this study investigated PVA fiber-reinforced concrete under combined sulfate attack and freeze–thaw cycles using PVA fiber volume fractions (0%, 0.1%, 0.3%, 0.5%) and salt-freeze cycles (0, 25, 50, 75, 100, 125, 150 cycles) as key variables. By testing the mechanical and microscopic properties of the specimens after salt-freeze, the degradation law of macroscopic performance and the evolution mechanism of microscopic structure of PVA fiber concrete under different volume fractions are analyzed, and the salt-freeze damage evolution equation is established based on the loss rate of relative dynamic elastic modulus. The results show that the addition of PVA fibers has no significant inhibitory effect on the surface erosion of concrete, and the degree of surface spalling of concrete still increases with the increase in the number of salt-freeze cycles. With the increase in the number of salt-freezing cycles, the mass, relative dynamic elastic modulus and cube compressive strength of the specimens first increase and then decrease, while the splitting tensile strength continuously decreases. The volume fraction of 0.3% PVA fibers has the most significant effect on improving the cube compressive strength and splitting tensile strength of concrete, and at the same time, it allows concrete to reach its best salt-freezing resistance. PVA fibers contribute to a denser microstructure, inhibit the development of micro-cracks, delay the formation of erosion products, and enhance the salt-freezing resistance of concrete. The damage degree D of relative dynamic elastic modulus for PVA fiber concrete exhibits a cubic functional relationship with the number of salt-freeze cycles N, and the correlation coefficient R2 is greater than 0.88. The equation can accurately describe the damage and deterioration law of PVA fiber concrete in the salt-freeze coupling environment. In contrast to numerous studies on single-factor exposures, this work provides new insights into the degradation mechanisms and optimal fiber dose for PVA fiber concrete under the synergistic effect of combined sulfate and freeze-thaw attacks, a critical scenario for infrastructure in cold saline regions. This study can provide theoretical guidance for the durability assessment and engineering application of PVA fiber concrete in cold and saline regions. Full article
(This article belongs to the Section Construction and Building Materials)
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13 pages, 1372 KB  
Article
Inhibition of Low-Density Lipoprotein Oxidation by Cysteamine, Cystamine, Cysteine and Cystine at Lysosomal pH and pH 7.4
by Emily J. Parkes, Ana M. Cruz, Amanpreet Kaur, Georgina R. Clark, Thomas E. Pulford, Christopher Ness, Feroz Ahmad, Yichuan Wen and David S. Leake
Antioxidants 2026, 15(1), 20; https://doi.org/10.3390/antiox15010020 - 22 Dec 2025
Viewed by 423
Abstract
LDL can be oxidised in the lysosomes of macrophages. Cysteamine, a thiol antioxidant that accumulates in lysosomes, inhibits the oxidation of LDL by iron at lysosomal pH (pH 4.5) and protects against atherosclerosis in mice. We have investigated the effects of cysteamine and [...] Read more.
LDL can be oxidised in the lysosomes of macrophages. Cysteamine, a thiol antioxidant that accumulates in lysosomes, inhibits the oxidation of LDL by iron at lysosomal pH (pH 4.5) and protects against atherosclerosis in mice. We have investigated the effects of cysteamine and its related thiol cysteine and their disulfides on LDL oxidation by iron or copper at both pH 4.5 and 7.4. The oxidation of LDL by ferrous iron (5 µM) at pH 4.5 was delayed 12.9-fold by 100 µM cysteamine and 5.6-fold by 100 µM cysteine. Cystamine and cystine (the disulfide oxidation products of cyteamine and cysteine, respectively) did not inhibit LDL oxidation by ferrous iron at pH 4.5. LDL oxidation by 5 µM copper at pH 4.5 was delayed about 2-fold by 100 µM of the thiols cysteamine and cysteine, but there was little effect of the disulfides cystamine and cystine. Cysteamine and cystine did not inhibit the oxidation of LDL by ferrous iron at pH 7.4 in a MOPS buffer and even accelerated LDL oxidation later in the incubation. Cysteine initially inhibited the oxidation of LDL by ferrous iron at pH 7.4, but increased it later. LDL oxidation by copper at pH 7.4 was delayed 7.8-fold by 100 µM cysteamine. Cysteine delayed LDL oxidation by copper at pH 7.4 to a similar extent as cysteamine but, unlike cysteamine, continued to decrease the rate of oxidation even after the period of total inhibition had ended. Cystamine had no effect on LDL oxidation by copper at pH 7.4, but cystine partially inhibited LDL oxidation. The effects of thiols and disulfides on LDL oxidation, therefore, depend not only on the metal ion catalysing the oxidation but also on the pH of the environment. Full article
(This article belongs to the Section Aberrant Oxidation of Biomolecules)
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19 pages, 1609 KB  
Article
Biotechnological Potential of Metschnikowia pulcherrima Yeasts for Biomass Production in Agricultural Biocontrol
by Zofia Perek, Tomasz Boruta, Anna Ścigaczewska, Marcin Bizukojć and Beata Gutarowska
Appl. Sci. 2025, 15(24), 13236; https://doi.org/10.3390/app152413236 - 17 Dec 2025
Viewed by 358
Abstract
This study aimed to select Metschnikowia pulcherrima strains with antimicrobial potential and high biomass content, optimize their cultivation conditions, evaluate growth characteristics at different scales, and assess antimicrobial activity on apple plants (Malus domestica cv. Golden Delicious) infected with phytopathogens. Of the [...] Read more.
This study aimed to select Metschnikowia pulcherrima strains with antimicrobial potential and high biomass content, optimize their cultivation conditions, evaluate growth characteristics at different scales, and assess antimicrobial activity on apple plants (Malus domestica cv. Golden Delicious) infected with phytopathogens. Of the nine tested strains, M. pulcherrima D2 was selected for its strong inhibitory activity against all tested phytopathogenic molds: Venturia inaequalis, Botrytis cinerea, Phoma exigua, Colletotrichum coccodes, Monilia laxa, Alternaria alternata, Alternaria tenuissima, Fusarium sambucinum, and Fusarium oxysporum, both in vitro on laboratory media (inhibition zones from 13.5 to 35.0 mm) and in vivo on stems, leaves, flowers, and fruits of apple. Morphological observations of treated plants showed the complete absence or significant delays of disease symptoms for up to 10 days. Disease symptoms for several pathogens (V. inaequalis, A. alternata, A. tenuissima, B. cinerea, F. sambucinum) remained reduced by ≥50% for up to 31 days post-treatment compared to the untreated control. Optimal cultivation conditions for M. pulcherrima D2 were established: a complex medium containing yeast extract (5.0 g/L), soy peptone (5.0 g/L), and glucose (2.6 g/L), at pH 5 and 25 °C, with shaking at 180 rpm, resulted in high biomass contents (107–108 CFU/mL). Scale-up in 5 L bioreactors confirmed efficient biomass production (108 CFU/mL and from 3.1 to 3.9 g/L of dry biomass). These findings highlight the strong biotechnological potential of M. pulcherrima D2 for the development of a biocontrol agent to protect apple fruits and trees against fungal phytopathogens. Full article
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15 pages, 3835 KB  
Article
High Temperature-Induced Suppression of Flower Bud Formation in Passion Fruit (Passiflora edulis f. flavicarpa)
by Xiuqing Wei, Yajun Tang, Weijie Huang, Ping Zhou, Liang Li, Dong Yu, Xujia Tang and Jiahui Xu
Horticulturae 2025, 11(12), 1526; https://doi.org/10.3390/horticulturae11121526 - 16 Dec 2025
Viewed by 422
Abstract
High temperature is a major environmental stress that severely limits passionfruit (Passiflora edulis) productivity by impairing floral initiation. However, the physiological and molecular mechanisms underlying this process remain poorly understood. In this study, we investigated the effects of varying durations and [...] Read more.
High temperature is a major environmental stress that severely limits passionfruit (Passiflora edulis) productivity by impairing floral initiation. However, the physiological and molecular mechanisms underlying this process remain poorly understood. In this study, we investigated the effects of varying durations and intensities of heat stress on flower bud differentiation in passionfruit. Our results showed that prolonged exposure to temperatures above 35 °C significantly delayed or completely inhibited bud formation, accompanied by altered carbohydrate and nitrogen metabolism, accumulation of osmolytes (soluble protein and proline), and dynamic changes in antioxidant enzyme activities (SOD, POD, CAT). Notably, short-term heat stress induced a transient increase in salicylic acid (SA) levels and upregulation of SA biosynthesis genes (PeEDS1.2, PeICS1) and WRKY transcription factors (PeWRKY11/15), which were associated with sustained floral initiation. In contrast, prolonged stress suppressed SA accumulation and signaling, leading to bud abortion. Comparative transcriptomic analysis further revealed enrichment of pathways related to secondary metabolite biosynthesis, plant hormone signal transduction, and phenylpropanoid biosynthesis under heat stress. These findings highlight the critical role of SA in balancing heat tolerance and reproductive development and provide candidate gene resources for the molecular breeding of heat-resistant passionfruit varieties. This study offers new insights into the thermotolerance mechanisms of fruit crops under sustained high-temperature stress. Full article
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26 pages, 5051 KB  
Article
Catalytically Active Recombinant Cysteine Proteases of Haemonchus contortus: Their Ability to Degrade Host Blood Proteins and Modulate Coagulation
by Athira C. Karunakaran, Mariam Bakshi, Arunraj M. Rajendrakumar, Jennifer H. Wilson-Welder, Raffi V. Aroian, Erich M. Schwarz, E. Jane Homan, Gary R. Ostroff, Ethiopia Beshah, Eliseo Miramontes, Marianne Dias Papadopoulos, Scott A. Bowdridge, Dante S. Zarlenga, Xiaoping Zhu and Wenbin Tuo
Int. J. Mol. Sci. 2025, 26(24), 12077; https://doi.org/10.3390/ijms262412077 - 16 Dec 2025
Viewed by 414
Abstract
Haemonchus contortus is a blood-feeding gastrointestinal nematode that significantly impacts the health and productivity of small ruminants. The burden of parasitism and the escalating incidence of anthelmintic resistance necessitate alternative control methods. Here, we characterize the enzymatic activities of five mammalian cell-expressed recombinant [...] Read more.
Haemonchus contortus is a blood-feeding gastrointestinal nematode that significantly impacts the health and productivity of small ruminants. The burden of parasitism and the escalating incidence of anthelmintic resistance necessitate alternative control methods. Here, we characterize the enzymatic activities of five mammalian cell-expressed recombinant H. contortus cysteine proteases (HcCPs), which include two cathepsin B-like proteins (HcCBP1 and HcCBP2) and three cysteine protease 1 proteins (HcCP1a, HcCP1b, and HcCP1c). We hypothesize that these enzymes degrade host blood proteins, thereby facilitating the parasite’s nutrient acquisition and survival. Using synthetic cathepsin (cat) substrates, we show that HcCBP2 was the only protein that exhibited high catB/L but low catB or catK activity, which was inhibited by the cysteine protease inhibitor E-64. All mHcCPs degraded fibrinogen (Fg), which led to delayed plasma clotting, reduced clot density, and lysed plasma clots. All HcCPs partially degraded hemoglobin (Hb), except for mHcCBP2, which degraded Hb and bovine serum albumin completely and bovine IgG partially in the presence of a reducing agent. In conclusion, by sustaining blood feeding and facilitating immune evasion and nutrient acquisition, the HcCPs may play an essential role in the parasite’s survival. Thus, vaccines or cysteine protease inhibitors targeting these parasitic enzymes may mitigate or prevent infections. Full article
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18 pages, 2985 KB  
Article
Bioprotective Potential of Pediococcus acidilactici L1 and Lactiplantibacillus plantarum HG1-1 in Harbin Red Sausage Under Vacuum Packaging
by Qiang Wang, Kaida Zhang, Qian Chen, Haotian Liu, Chao Zhang, Qian Liu and Baohua Kong
Foods 2025, 14(24), 4293; https://doi.org/10.3390/foods14244293 - 13 Dec 2025
Viewed by 399
Abstract
Effective biopreservation strategies are essential to maintain product quality and extend shelf life. However, the low storage temperature (4 °C) of low-temperature meat products limits the growth and activity of most protective cultures, highlighting the need for psychrotrophic strains. This study evaluated the [...] Read more.
Effective biopreservation strategies are essential to maintain product quality and extend shelf life. However, the low storage temperature (4 °C) of low-temperature meat products limits the growth and activity of most protective cultures, highlighting the need for psychrotrophic strains. This study evaluated the impact of various bioprotective cultures on the bacterial counts, physicochemical quality, flavor profile, and sensory characteristics of the Harbin red sausage under vacuum packaging for 28 days. In comparison with the control (uninoculated) and B2 (commercial Latilactobacillus sakei B2) groups, individual and mixed (1:1) inoculations with psychrotrophic Pediococcus acidilactici L1 and Lactiplantibacillus plantarum HG1-1 significantly inhibited the growth of Acinetobacter and Staphylococcus (p < 0.05), providing the sausage with superior color and texture and delaying lipid oxidation, thereby improving the sausage’s overall acceptability on day 28. The electronic nose analyses indicated that Harbin red sausages inoculated with individual and mixed cultures of Pe. acidilactici L1 and Lac. plantarum HG1-1 exhibited less development of odor compounds during storage. Overall, both individual and mixed inoculations with Pe. acidilactici L1 and Lac. plantarum HG1-1 showed superior bioprotective effects on Harbin red sausages under vacuum packaging compared with commercial Lat. sakei B2, with the mixed inoculation treatment being the most effective. Full article
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23 pages, 3362 KB  
Article
Washout-Filter-Based Stabilization Control for Continuous Ethanol Fermentation Under Delay-Induced Product Inhibition
by Chen Liang, Sichen Wu and Chi Zhai
Processes 2025, 13(12), 4022; https://doi.org/10.3390/pr13124022 - 12 Dec 2025
Viewed by 316
Abstract
Continuous ethanol fermentation is crucial for renewable bio-manufacturing, but delay-induced ethanol inhibition triggers self-oscillations via Hopf bifurcations, undermining productivity and stability. This study investigates instability mechanisms and proposes a washout-filter-aided control strategy. Using Hopf bifurcation theory, the critical delay time τc (20.97 [...] Read more.
Continuous ethanol fermentation is crucial for renewable bio-manufacturing, but delay-induced ethanol inhibition triggers self-oscillations via Hopf bifurcations, undermining productivity and stability. This study investigates instability mechanisms and proposes a washout-filter-aided control strategy. Using Hopf bifurcation theory, the critical delay time τc (20.97 h) was quantified, and it confirmed that τ > τc (intrinsic τ = 21.72 h) induces oscillations. Closed-loop analysis reveals that the filter extends τc to 25.57 h (e.g., K = 2, d = 0.5), expanding the stability margin by modulating ethanol dynamics through phase-shifted feedback. Numerical simulations and experimental validation demonstrate effective oscillation suppression, maintaining steady-state substrate (S* = 84.32 g/L), biomass (X* = 6.92 g/L), and ethanol (P* = 22.02 g/L) concentrations without sacrificing productivity. Unlike conventional methods, the strategy retains the system’s equilibrium structure, resists noise, and requires no additional hardware. This work bridges bifurcation analysis with practical control, offering a robust, scalable solution for industrial continuous ethanol production to mitigate delay-induced instabilities. Full article
(This article belongs to the Section Automation Control Systems)
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18 pages, 4665 KB  
Article
Geochemical and Spectroscopic Characteristics of Marine Crude Oil Cracking Under Overpressure: A Case Study of the Tarim Basin
by Xinyue Shi, Shangli Liu, Haifeng Gai, Peng Cheng and Hui Han
Processes 2025, 13(12), 3896; https://doi.org/10.3390/pr13123896 - 2 Dec 2025
Viewed by 377
Abstract
Deep and ultra-deep petroleum resources have become major contributors to petroleum reserves. The Tarim Basin has recently witnessed discoveries of several oil reservoirs at depths exceeding 8000 m, which extend the exploration depth limit for crude oil and light oil resources. To clarify [...] Read more.
Deep and ultra-deep petroleum resources have become major contributors to petroleum reserves. The Tarim Basin has recently witnessed discoveries of several oil reservoirs at depths exceeding 8000 m, which extend the exploration depth limit for crude oil and light oil resources. To clarify the role of overpressure during the critical stage of crude oil cracking (Easy Ro ≈ 1.0–2.0%), this study conducted low-temperature, long-duration, overpressure (150 MPa) gold tube pyrolysis experiments on marine crude oil from the Tarim Basin. Comprehensive analysis of the cracking products (C1–C30₊) revealed significant differences in the thermal stability and cracking behavior of hydrocarbon molecules with different chain lengths: long-chain hydrocarbons (C12₊) were continuously consumed as the primary reactants, whereas short-chain hydrocarbons (C6–C12) initially formed as products and subsequently underwent secondary cracking as reactants. During this process, overpressure played a critical role in delaying the yield peak of light hydrocarbons and suppressing their secondary cracking. This mechanism resulted in a slower increase in gaseous hydrocarbon yield under overpressure conditions, and the carbon isotopic composition clearly recorded a shift in the cracking precursors from heavy to light hydrocarbons. Furthermore, fluorescence lifetime, as a sensitive spectroscopic indicator, exhibited delayed decay under overpressure, confirming the inhibition of aromatization and polymerization reactions by overpressure. By illuminating the sequential nature of hydrocarbon cracking and the moderating influence of overpressure at molecular and spectroscopic levels, this work offers crucial evidence for understanding multi-phase hydrocarbon coexistence and forecasting the preservation depth of discrete-phase crude oil in the Shuntuoguole area. Full article
(This article belongs to the Section Energy Systems)
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33 pages, 891 KB  
Review
Advances in Therapeutics Research for Demyelinating Diseases
by Jinhui Jiang, Yuchen Sun, Yuan Ma, Chenhui Xu, Xiaofeng Zhao and Hui Fu
Pharmaceuticals 2025, 18(12), 1835; https://doi.org/10.3390/ph18121835 - 1 Dec 2025
Viewed by 1513
Abstract
Demyelinating diseases comprise a group of chronic and debilitating neurological disorders, with the destruction of the myelin sheath serving as the core pathological hallmark. The central pathogenesis involves immune-mediated damage to oligodendrocytes (Ols) and myelin breakdown, accompanied by a vicious cycle of neuroinflammation [...] Read more.
Demyelinating diseases comprise a group of chronic and debilitating neurological disorders, with the destruction of the myelin sheath serving as the core pathological hallmark. The central pathogenesis involves immune-mediated damage to oligodendrocytes (Ols) and myelin breakdown, accompanied by a vicious cycle of neuroinflammation and impaired epigenetic repair. Current therapeutic strategies, including conventional immunomodulatory agents to targeted monoclonal antibodies, effectively control disease relapses but exhibit limited efficacy in promoting neural repair. Consequently, research focus is increasingly shifting towards neuroprotective and remyelination strategies. In this context, Emerging therapeutic promise stems primarily from two fronts: the advent of novel pharmaceuticals, such as remyelination-promoting drugs targeting oligodendrocyte maturation, interventions inhibiting epigenetic silencing, signal pathway inhibitors, and natural products derived from traditional Chinese medicine; the development of innovative technologies, including cell therapies, gene therapy, exosome and nanoparticle-based drug delivery systems, as well as extracellular protein degradation platforms. Nevertheless, drug development still faces challenges such as disease heterogeneity, limited blood–brain barrier penetration, long-term safety, and difficulties in translating findings from preclinical models. Future efforts should emphasize precision medicine, multi-target synergistic therapies, and the development of intelligent delivery systems, with the ultimate goal of achieving a paradigm shift from delaying disability progression to functional neural reconstruction. Full article
(This article belongs to the Section Medicinal Chemistry)
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14 pages, 9457 KB  
Article
Mechanistic Insights into the Effect of Ca on the Oxidation Behavior of Fe3O4: A Combined DFT and AIMD Study
by Huiqing Jiang, Yaozu Wang, Zhengjian Liu, Xin Yang, Fangyu Guo and Jianliang Zhang
Metals 2025, 15(12), 1321; https://doi.org/10.3390/met15121321 - 29 Nov 2025
Viewed by 363
Abstract
With the increasing adoption of traveling grate machines, increasing the proportion of pellets in blast furnace burdens has become a key strategy for reducing carbon emissions in ironmaking. Magnetite (Fe3O4) is not only the core raw material for pellet [...] Read more.
With the increasing adoption of traveling grate machines, increasing the proportion of pellets in blast furnace burdens has become a key strategy for reducing carbon emissions in ironmaking. Magnetite (Fe3O4) is not only the core raw material for pellet production but also serves as an important transition metal oxide catalyst, widely used in various fields due to its unique electronic structure and surface activity. This study employed density functional theory (DFT) and ab initio molecular dynamics (AIMD) to simulate the oxidation process of a Ca-doped Fe3O4 (110) surface at 1073 K, revealing the inhibition mechanism of the gangue element Ca and its impact on surface catalytic activity at the atomic scale. The results demonstrate that Ca segregates on the Fe3O4 surface, where it adsorbs and activates O2 molecules, thereby delaying O2 migration to active iron bridge sites and subsequent dissociation, which ultimately inhibits the oxidation kinetics. Electronic structure analysis indicates that the breakage of the O–O bond is accompanied by a sharp decrease in system energy (stabilizing at approximately −509 eV); it also clearly elucidates the charge transfer process and the mechanism of Fe-O bond formation during this exothermic reaction. This research provides a theoretical foundation for the development of fluxed pellets and high-temperature-resistant catalysts. Full article
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20 pages, 6780 KB  
Article
The Mitigating Effect and Mechanism of Polydeoxyribonucleotide Against Zoledronic Acid-Induced Growth Suppression of Human Gingival Fibroblasts
by Shailashree Pachhapure, Young-Min Shin, Duk Gyu Kim, Dong-Rak Choi, Jong-IL Yun, Jae-Hong Kim and Byeong-Churl Jang
Int. J. Mol. Sci. 2025, 26(23), 11367; https://doi.org/10.3390/ijms262311367 - 24 Nov 2025
Viewed by 768
Abstract
Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is widely used to treat osteoporosis and bone metastases. However, its clinical application is limited by adverse effects, notably bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is associated with cytotoxicity in oral mucosal cells. Polydeoxyribonucleotide (PDRN), a [...] Read more.
Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is widely used to treat osteoporosis and bone metastases. However, its clinical application is limited by adverse effects, notably bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is associated with cytotoxicity in oral mucosal cells. Polydeoxyribonucleotide (PDRN), a salmon sperm-derived DNA polymer with regenerative and anti-inflammatory properties, has shown therapeutic potential in tissue repair; however, its ability to mitigate ZA-induced cytotoxicity remains poorly understood. Here, we investigated the molecular mechanisms of ZA-induced toxicity in HGF-1 cells, a human gingival fibroblast line, and evaluated the protective effects of PDRN. ZA treatment (50 µM, 48 h) significantly inhibited HGF-1 cell growth, accompanied by reduced phosphorylation of protein kinase B (PKB) and signal transducer and activator of transcription 3 (STAT-3), along with increased phosphorylation of TANK-binding kinase 1 (TBK1). TBK1 silencing restored cell growth under ZA exposure, whereas silencing PKB or STAT-3 further suppressed cell growth even without ZA. Co-treatment with PDRN (100 µg/mL) effectively prevented and reversed ZA-induced HGF-1 cytotoxicity. Mechanistically, PDRN inhibited ZA-induced TBK1 phosphorylation and partially restored PKB phosphorylation, though it did not reverse the reduction in p-STAT-3. Additionally, ZA significantly elevated intracellular reactive oxygen species (ROS) levels at 8 h, which were attenuated by PDRN. The antioxidant N-acetylcysteine (NAC) similarly reduced ZA-induced ROS and p-TBK1 levels and improved cell growth, although it had limited effects on p-PKB at 8 h. Importantly, delayed PDRN treatment following ZA exposure reversed ZA-induced cell growth inhibition and TBK1 activation in a dose- and time-dependent manner. In summary, these findings demonstrate that ZA suppresses HGF-1 cell growth through ROS production, TBK1 activation, and inhibition of PKB and STAT-3, whereas PDRN counteracts these effects primarily by suppressing TBK1 activation and oxidative stress. Full article
(This article belongs to the Special Issue Application of Biotechnology to Dental Treatment)
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16 pages, 4366 KB  
Article
Influence of Fly Ash on the Macro Properties and Mineral Crystal Characteristics of Alkali-Activated Slag Grouting Materials
by Guodong Huang, Jiahao Xu, Jun Qi, Fengan Zhang and Baoxuan Dou
Crystals 2025, 15(11), 999; https://doi.org/10.3390/cryst15110999 - 20 Nov 2025
Viewed by 361
Abstract
Alkali-activated slag grouting materials exhibited excellent mechanical properties but still faced technical challenges such as insufficient fluidity and overly rapid setting. To enhance their workability, this study introduced fly ash as a modifying component, leveraging its morphological and activity effects to systematically investigate [...] Read more.
Alkali-activated slag grouting materials exhibited excellent mechanical properties but still faced technical challenges such as insufficient fluidity and overly rapid setting. To enhance their workability, this study introduced fly ash as a modifying component, leveraging its morphological and activity effects to systematically investigate the composite influence on fluidity, setting time, and compressive strength. The mechanism was further elucidated through microstructural analysis of the mineral crystallization characteristics of polycondensation products. The results indicated that with increasing fly ash content, the fluidity of the grouting material continuously improved, and both the initial and final setting times were significantly prolonged, albeit at the expense of a gradual decline in compressive strength. At a 20% fly ash content, the fluidity spread increased to 292 mm, the initial and final setting times were extended to 70 min and 103 min, respectively, while the 1 d and 28 d compressive strengths reached 11.8 MPa and 48.1 MPa, achieving an optimal overall performance that met practical grouting requirements. Microscopic analysis revealed that fly ash enhanced the rheological properties and delayed the setting process through the “ball-bearing effect” and its low early-age reactivity. However, as the fly ash content rose, the active calcium content in the system continuously decreased, inhibiting the formation and development of key mineral crystals such as calcium silicate and calcium aluminosilicate, thereby leading to the reduction in compressive strength. Full article
(This article belongs to the Section Crystal Engineering)
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24 pages, 2430 KB  
Article
Effect of Irrigation with Saline Water on Germination, Physiology, Growth, and Yield of Durum Wheat Varieties on Silty Clay Soil
by Khadija Manhou, Rachid Moussadek, Houria Dakak, Abdelmjid Zouahri, Ahmed Ghanimi, Hatim Sanad, Majda Oueld Lhaj and Driss Hmouni
Agriculture 2025, 15(22), 2364; https://doi.org/10.3390/agriculture15222364 - 14 Nov 2025
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Abstract
Freshwater scarcity in arid regions forces farmers to use saline water, reducing durum wheat (Triticum turgidum L. subsp. durum) productivity, particularly during early growth stages. This study evaluated two Moroccan varieties, Faraj and Nachit, on silty clay soil under five salinity [...] Read more.
Freshwater scarcity in arid regions forces farmers to use saline water, reducing durum wheat (Triticum turgidum L. subsp. durum) productivity, particularly during early growth stages. This study evaluated two Moroccan varieties, Faraj and Nachit, on silty clay soil under five salinity levels (0.2, 4, 8, 12, and 16 dS m−1) in a randomized complete block design with three replications, aiming to identify tolerance thresholds and characterize physiological and agronomic responses. Key traits measured included germination percentage, germination stress index, mean germination time, root and coleoptile length, plant height, leaf number, chlorophyll fluorescence, grain yield, weight of 200 grains, and straw yield. Germination percentage declined from 8 dS m−1, with delayed germination and inhibited vegetative growth at higher salinity. Both varieties maintained grain yield up to 8 dS m−1 and weight of 200 grains and straw yield up to 12 dS m−1, with Nachit showing higher tolerance. Multivariate analyses, including principal component analysis and heatmaps, linked soil sodium, chloride, and electrical conductivity negatively to growth and yield, whereas potassium, calcium, and magnesium supported plant growth and physiological activity. These findings provide insights for breeding and irrigation strategies to sustain durum wheat under salinity stress. Full article
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