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39 pages, 8119 KiB  
Article
Magmatic Redox Evolution and Porphyry–Skarn Transition in Multiphase Cu-Mo-W-Au Systems of the Eocene Tavşanlı Belt, NW Türkiye
by Hüseyin Kocatürk, Mustafa Kumral, Hüseyin Sendir, Mustafa Kaya, Robert A. Creaser and Amr Abdelnasser
Minerals 2025, 15(8), 792; https://doi.org/10.3390/min15080792 - 28 Jul 2025
Abstract
This study explores the magmatic and hydrothermal evolution of porphyry–skarn–transitional Cu-Mo-W-Au systems within the Nilüfer Mineralization Complex (NMC), located in the westernmost segment of the Eocene Tavşanlı Metallogenic Belt, NW Türkiye. Through integration of field data, whole-rock geochemistry, Re–Os molybdenite dating, and amphibole–biotite [...] Read more.
This study explores the magmatic and hydrothermal evolution of porphyry–skarn–transitional Cu-Mo-W-Au systems within the Nilüfer Mineralization Complex (NMC), located in the westernmost segment of the Eocene Tavşanlı Metallogenic Belt, NW Türkiye. Through integration of field data, whole-rock geochemistry, Re–Os molybdenite dating, and amphibole–biotite mineral chemistry, the petrogenetic controls on mineralization across four spatially associated mineralized regions (Kirazgedik, Güneybudaklar, Kozbudaklar, and Delice) were examined. The earliest and thermally most distinct phase is represented by the Kirazgedik porphyry system, characterized by high temperature (~930 °C), oxidized quartz monzodioritic intrusions emplaced at ~2.7 kbar. Rising fO2 and volatile enrichment during magma ascent facilitated structurally focused Cu-Mo mineralization. At Güneybudaklar, Re–Os geochronology yields an age of ~49.9 Ma, linking Mo- and W-rich mineralization to a transitional porphyry–skarn environment developed under moderately oxidized (ΔFMQ + 1.8 to +0.5) and hydrous (up to 7 wt.% H2O) magmatic conditions. Kozbudaklar represents a more reduced, volatile-poor skarn system, leading to Mo-enriched scheelite mineralization typical of late-stage W-skarns. The Delice system, developed at the contact of felsic cupolas and carbonates, records the broadest range of redox and fluid compositions. Mixed oxidized–reduced fluid signatures and intense fluid–rock interaction reflect complex, multistage fluid evolution involving both magmatic and external inputs. Geochemical and mineralogical trends—from increasing silica and Rb to decreasing Sr and V—trace a systematic evolution from mantle-derived to felsic, volatile-rich magmas. Structurally, mineralization is controlled by oblique fault zones that localize magma emplacement and hydrothermal flow. These findings support a unified genetic model in which porphyry and skarn mineralization styles evolved continuously from multiphase magmatic systems during syn-to-post-subduction processes, offering implications for exploration models in the Western Tethyan domain. Full article
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14 pages, 1343 KiB  
Article
Role of Plasma-Derived Exosomal MicroRNAs in Mediating Type 2 Diabetes Remission
by Sujing Wang, Shuxiao Shi, Xuanwei Jiang, Guangrui Yang, Deshan Wu, Kexin Li, Victor W. Zhong and Xihao Du
Nutrients 2025, 17(15), 2450; https://doi.org/10.3390/nu17152450 - 27 Jul 2025
Abstract
Objective: This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. Methods: A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month [...] Read more.
Objective: This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. Methods: A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month intensive weight loss phase consuming LCD (815–835 kcal/day) and a 3-month weight maintenance phase (N = 32). Sixteen participants were randomly selected for characterization of plasma-derived exosomal miRNA profiles at baseline, 3 months, and 6 months using small RNA sequencing. Linear mixed-effects models were used to identify differentially expressed exosomal miRNAs between responders and non-responders. Pathway enrichment analyses were conducted using target mRNAs of differentially expressed miRNAs. Logistic regression models assessed the predictive value of differentially expressed miRNAs for T2D remission. Results: Among the 16 participants, 6 achieved weight loss ≥10% and 12 achieved T2D remission. Eighteen exosomal miRNAs, including miR-92b-3p, miR-495-3p, and miR-452b-5p, were significantly associated with T2D remission and weight loss. Pathway analyses revealed enrichment in PI3K-Akt pathway, FoxO signaling pathway, and insulin receptor binding. The addition of individual miRNAs including miR-15b-3p, miR-26a-5p, and miR-3913-5p to base model improved the area under the curve values by 0.02–0.08 at 3 months and by 0.02–0.06 at 6 months for T2D remission. Conclusions: This study identified exosomal miRNAs associated with T2D remission and weight loss following LCD intervention. Several exosomal miRNAs might serve as valuable predictors of T2D remission in response to LCD intervention. Full article
(This article belongs to the Special Issue Nutrition for Patients with Diabetes and Clinical Obesity)
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15 pages, 1846 KiB  
Article
Synthesis of Monothiacalix[4]arene Using the Fragment Condensation Approach
by Daniel Kortus, Oliver Moravec, Hynek Varga, Michal Churý, Kamil Mamleev, Jan Čejka, Hana Dvořáková and Pavel Lhoták
Molecules 2025, 30(15), 3145; https://doi.org/10.3390/molecules30153145 - 27 Jul 2025
Abstract
The article describes a simple and scalable preparation of 2-monothiacalix[4]arene 7, the simplest representative of the mixed-bridged (CH2 and S) calix[4]arenes. The synthesis is based on the condensation of linear building blocks (bisphenols), which are relatively readily available, and allows, depending [...] Read more.
The article describes a simple and scalable preparation of 2-monothiacalix[4]arene 7, the simplest representative of the mixed-bridged (CH2 and S) calix[4]arenes. The synthesis is based on the condensation of linear building blocks (bisphenols), which are relatively readily available, and allows, depending on the conditions, the use of two alternative reaction routes that provide macrocycle 7 in high yield. The dynamic behavior of the basic macrocyclic skeleton was investigated using NMR spectroscopy at variable temperatures. High-temperature measurements showed that compound 7 undergoes a conecone equilibrium with activation free energy ΔG# of the inversion process of 63 kJ·mol−1. Interestingly, the same barrier for the oxidized sulfone derivative 14 shows a value of 60 kJ·mol−1, indicating weakened hydrogen bonds at the lower rim of the calixarene. The same was also confirmed at low temperatures, when barriers to changing the direction of the cyclic hydrogen bond arrays (flip-flop mechanism) were determined (compare ΔG# = 44 kJ·mol−1 for 7 vs. ΔG# = 40 kJ·mol−1 for 14). Full article
(This article belongs to the Special Issue Organosulfur and Organoselenium Chemistry II)
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22 pages, 17693 KiB  
Article
Mooring Observations of Typhoon Trami (2024)-Induced Upper-Ocean Variability: Diapycnal Mixing and Internal Wave Energy Characteristics
by Letian Chen, Xiaojiang Zhang, Ze Zhang and Weimin Zhang
Remote Sens. 2025, 17(15), 2604; https://doi.org/10.3390/rs17152604 - 27 Jul 2025
Abstract
High-resolution mooring observations captured diverse upper-ocean responses during typhoon passage, showing strong agreement with satellite-derived sea surface temperature and salinity. Analysis indicates that significant wind-induced mixing drove pronounced near-surface cooling and salinity increases at the mooring site. This mixing enhancement was predominantly governed [...] Read more.
High-resolution mooring observations captured diverse upper-ocean responses during typhoon passage, showing strong agreement with satellite-derived sea surface temperature and salinity. Analysis indicates that significant wind-induced mixing drove pronounced near-surface cooling and salinity increases at the mooring site. This mixing enhancement was predominantly governed by rapid intensification of near-inertial shear in the surface layer, revealed by mooring observations. Unlike shear instability, near-inertial horizontal kinetic energy displays a unique vertical distribution, decreasing with depth before rising again. Interestingly, the subsurface peak in diurnal tidal energy coincides vertically with the minimum in near-inertial energy. While both barotropic tidal forcing and stratification changes negligibly influence diurnal tidal energy emergence, significant energy transfer occurs from near-inertial internal waves to the diurnal tide. This finding highlights a critical tide–wave interaction process and demonstrates energy cascading within the oceanic internal wave spectrum. Full article
(This article belongs to the Special Issue Remote Sensing for Ocean-Atmosphere Interaction Studies)
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29 pages, 12355 KiB  
Article
Short- and Long-Term Mechanical and Durability Performance of Concrete with Copper Slag and Recycled Coarse Aggregate Under Magnesium Sulfate Attack
by Yimmy Fernando Silva, Claudia Burbano, Eduardo J. Rueda, Arturo Reyes-Román and Gerardo Araya-Letelier
Appl. Sci. 2025, 15(15), 8329; https://doi.org/10.3390/app15158329 - 26 Jul 2025
Viewed by 61
Abstract
Sustainability in the construction sector has become a fundamental objective for mitigating escalating environmental challenges; given that concrete is the most widely used man-made material, extending its service life is therefore critical. Among durability concerns, magnesium sulfate (MgSO4) attack is particularly [...] Read more.
Sustainability in the construction sector has become a fundamental objective for mitigating escalating environmental challenges; given that concrete is the most widely used man-made material, extending its service life is therefore critical. Among durability concerns, magnesium sulfate (MgSO4) attack is particularly deleterious to concrete structures. Therefore, this study investigates the short- and long-term performance of concrete produced with copper slag (CS)—a massive waste generated by copper mining activities worldwide—employed as a supplementary cementitious material (SCM), together with recycled coarse aggregate (RCA), obtained from concrete construction and demolition waste, when exposed to MgSO4. CS was used as a 15 vol% cement replacement, while RCA was incorporated at 0%, 20%, 50%, and 100 vol%. Compressive strength, bulk density, water absorption, and porosity were measured after water curing (7–388 days) and following immersion in a 5 wt.% MgSO4 solution for 180 and 360 days. Microstructural characteristics were assessed using scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis with its differential thermogravimetric derivative (TG-DTG), and Fourier transform infrared spectroscopy (FTIR) techniques. The results indicated that replacing 15% cement with CS reduced 7-day strength by ≤10%, yet parity with the reference mix was reached at 90 days. Strength losses increased monotonically with RCA content. Under MgSO4 exposure, all mixtures experienced an initial compressive strength gain during the short-term exposures (28–100 days), attributed to the pore-filling effect of expansive sulfate phases. However, at long-term exposure (180–360 days), a clear strength decline was observed, mainly due to internal cracking, brucite formation, and the transformation of C–S–H into non-cementitious M–S–H gel. Based on these findings, the combined use of CS and RCA at low replacement levels shows potential for producing environmentally friendly concrete with mechanical and durability performance comparable to those of concrete made entirely with virgin materials. Full article
21 pages, 3566 KiB  
Article
Dendrometer-Based Analysis of Intra-Annual Growth and Water Status in Two Pine Species in a Mediterranean Forest Stand Under a Semi-Arid Climate
by Mehmet S. Özçelik
Forests 2025, 16(8), 1229; https://doi.org/10.3390/f16081229 - 26 Jul 2025
Viewed by 65
Abstract
Stem radius growth (GRO), tree water deficit (TWD), and maximum daily shrinkage (MDS) were monitored throughout 2023 in a semi-arid Mediterranean forest stand in Burdur, Türkiye, where Pinus nigra subsp. pallasiana (Lamb.) Holmboe and Pinus brutia Ten. naturally co-occur. These indicators, derived from [...] Read more.
Stem radius growth (GRO), tree water deficit (TWD), and maximum daily shrinkage (MDS) were monitored throughout 2023 in a semi-arid Mediterranean forest stand in Burdur, Türkiye, where Pinus nigra subsp. pallasiana (Lamb.) Holmboe and Pinus brutia Ten. naturally co-occur. These indicators, derived from electronic band dendrometers, were analyzed in relation to key climatic variables. Results indicated that P. brutia had a longer growth period, while P. nigra exhibited a higher average daily increment under the environmental conditions of 2023 at the study site. Annual stem growth was nearly equal for both species. Based on dendrometer observations, P. brutia exhibited lower normalized TWD and higher normalized MDS values under varying vapor pressure deficit (VPD) and soil water potential (SWP) conditions. A linear mixed-effects model further confirmed that P. brutia consistently maintained lower TWD than P. nigra across a wide climatic range, suggesting a comparatively lower degree of drought-induced water stress. GRO was most influenced by air temperature and VPD, and negatively by SWP. TWD was strongly affected by both VPD and SWP, while MDS was primarily linked to minimum air temperature and VPD. Moreover, MDS in P. brutia appeared more sensitive to climate variability compared to P. nigra. Although drought limited stem growth in both species during the study year, the lower TWD and higher MDS observed in P. brutia may indicate distinct physiological strategies for coping with drought. These findings offer preliminary insights into interspecific differences in water regulation under the particular climatic conditions observed during the study year in this semi-arid Mediterranean ecosystem. Full article
(This article belongs to the Section Forest Ecophysiology and Biology)
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20 pages, 1481 KiB  
Article
Experimental and Kinetic Modelling Study of the Heterogeneous Catalytic Conversion of Bioethanol into n-Butanol Using MgO–Al2O3 Mixed Oxide Catalyst
by Amosi Makoye, Anna Vikár, András Bence Nacsa, Róbert Barthos, József Valyon, Ferenc Lónyi and Tibor Nagy
Catalysts 2025, 15(8), 709; https://doi.org/10.3390/catal15080709 - 25 Jul 2025
Viewed by 90
Abstract
Ethanol upgrading via catalytic C–C coupling, commonly known as the Guerbet reaction, offers a sustainable route to produce 1-butanol, a high-performance biofuel. To address gaps in the mechanistic understanding of the catalytic reaction, we investigated the process involving a fixed-bed reactor, operated at [...] Read more.
Ethanol upgrading via catalytic C–C coupling, commonly known as the Guerbet reaction, offers a sustainable route to produce 1-butanol, a high-performance biofuel. To address gaps in the mechanistic understanding of the catalytic reaction, we investigated the process involving a fixed-bed reactor, operated at 275–325 °C, 21 bar, and weight hourly space velocities of 0.25–2.5 gEtOH/(gcat·h), using helium as a carrier gas, with a 5:1 He/EtOH molar ratio. The catalyst was a MgO–Al2O3 mixed oxide (Mg/Al = 2:1), derived from a hydrotalcite precursor. A detailed kinetic model was developed, encompassing 15 species and 27 reversible steps (10 sorption and 17 reaction steps), within a 1+1D sorption–reaction–transport framework. Four C4-forming pathways were included: aldol condensation to form crotonaldehyde, semi-direct coupling to form butyraldehyde and crotyl alcohol, and direct coupling to form 1-butanol. To avoid overfitting, Arrhenius parameters were grouped by reaction type, resulting in sixty rate parameters and one active site-specific density parameter. The optimized model achieved high accuracy, with an average prediction error of 1.44 times the experimental standard deviation. The mechanistic analysis revealed aldol condensation as the dominant pathway below 335 °C, with semi-direct coupling to crotyl alcohol prevailing above 340 °C. The resulting model provides a robust framework for understanding and predicting complex reaction networks in ethanol upgrading systems. Full article
(This article belongs to the Special Issue Biomass Catalytic Conversion to Value-Added Chemicals)
24 pages, 10881 KiB  
Article
Dynamics of Water Quality in the Mirim–Patos–Mangueira Coastal Lagoon System with Sentinel-3 OLCI Data
by Paula Andrea Contreras Rojas, Felipe de Lucia Lobo, Wesley J. Moses, Gilberto Loguercio Collares and Lino Sander de Carvalho
Geomatics 2025, 5(3), 36; https://doi.org/10.3390/geomatics5030036 - 25 Jul 2025
Viewed by 108
Abstract
The Mirim–Patos–Mangueira coastal lagoon system provides a wide range of ecosystem services. However, its vast territorial extent and the political boundaries that divide it hinder integrated assessments, especially during extreme hydrological events. This study is divided into two parts. First, we assessed the [...] Read more.
The Mirim–Patos–Mangueira coastal lagoon system provides a wide range of ecosystem services. However, its vast territorial extent and the political boundaries that divide it hinder integrated assessments, especially during extreme hydrological events. This study is divided into two parts. First, we assessed the spatial and temporal patterns of water quality in the lagoon system using Sentinel-3/OLCI satellite imagery. Atmospheric correction was performed using ACOLITE, followed by spectral grouping and classification into optical water types (OWTs) using the Sentinel Applications Platform (SNAP). To explore the behavior of water quality parameters across OWTs, Chlorophyll-a and turbidity were estimated using semi-empirical algorithms specifically designed for complex inland and coastal waters. Results showed a gradual increase in mean turbidity from OWT 2 to OWT 6 and a rise in chlorophyll-a from OWT 2 to OWT 4, with a decline at OWT 6. These OWTs correspond, in general terms, to distinct water masses: OWT 2 to clearer waters, OWT 3 and 4 to intermediate/mixed conditions, and OWT 6 to turbid environments. In the second part, we analyzed the response of the Patos Lagoon to flooding in Rio Grande do Sul during an extreme weather event in May 2024. Satellite-derived turbidity estimates were compared with in situ measurements, revealing a systematic underestimation, with a negative bias of 2.6%, a mean relative error of 78%, and a correlation coefficient of 0.85. The findings highlight the utility of OWT classification for tracking changes in water quality and support the use of remote sensing tools to improve environmental monitoring in data-scarce regions, particularly under extreme hydrometeorological conditions. Full article
(This article belongs to the Special Issue Advances in Ocean Mapping and Hydrospatial Applications)
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21 pages, 1471 KiB  
Article
Impact of Basalt Rock Powder on Ryegrass Growth and Nutrition on Sandy and Loamy Acid Soils
by Charles Desmalles, Lionel Jordan-Meille, Javier Hernandez, Cathy L. Thomas, Sarah Dunham, Feifei Deng, Steve P. McGrath and Stephan M. Haefele
Agronomy 2025, 15(8), 1791; https://doi.org/10.3390/agronomy15081791 - 25 Jul 2025
Viewed by 234
Abstract
Enhanced weathering of silicate rocks in agriculture is an option for atmospheric CO2 removal and fertility improvement. The objective of our work is to characterise some of the agricultural consequences of a basaltic powder amendment on soil-crop systems. Two doses of basalt [...] Read more.
Enhanced weathering of silicate rocks in agriculture is an option for atmospheric CO2 removal and fertility improvement. The objective of our work is to characterise some of the agricultural consequences of a basaltic powder amendment on soil-crop systems. Two doses of basalt (80 and 160 t ha−1) were applied to two types of slightly acid soils (sandy or silty clayey), derived from long-term trials at Bordeaux (INRAE, France) and Rothamsted Research (England), respectively. For each soil, half of the pots were planted with ryegrass; the other half were left bare. Thus, the experiment had twelve treatments with four replications per treatment. Soil pH increased with the addition of basalt (+0.8 unit), with a 5% equivalence of that of reactive chalk. The basalt contained macro- and micronutrients. Some cations extractable in the basalt before being mixed to the soil became more extractable with increased weathering, independent of plant cover. Plant uptake generally increased for macronutrients and decreased for micronutrients, due to increased stock (macro) and reduced availability (micronutrients and P), related to pH increases. K supplied in the basalt was responsible for a significant increase in plant yield on the sandy soil, linked to an average basalt K utilisation efficiency of 33%. Our general conclusion is that rock dust applications have to be re-evaluated at each site with differing soil characteristics. Full article
(This article belongs to the Section Grassland and Pasture Science)
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17 pages, 1535 KiB  
Article
Isobaric Vapor-Liquid Equilibrium of Biomass-Derived Ethyl Levulinate and Ethanol at 40.0, 60.0 and 80.0 kPa
by Wenteng Bo, Xinghua Zhang, Qi Zhang, Lungang Chen, Jianguo Liu, Longlong Ma and Shengyong Ma
Energies 2025, 18(15), 3939; https://doi.org/10.3390/en18153939 - 24 Jul 2025
Viewed by 152
Abstract
Isobaric vapor-liquid equilibrium (VLE) data for binary mixtures of biomass–derived ethyl levulinate and ethanol were measured using an apparatus comprising a modified Rose-Williams still and a condensation system. Measurements were taken at temperatures ranging from 329.58 K to 470.00 K and pressures of [...] Read more.
Isobaric vapor-liquid equilibrium (VLE) data for binary mixtures of biomass–derived ethyl levulinate and ethanol were measured using an apparatus comprising a modified Rose-Williams still and a condensation system. Measurements were taken at temperatures ranging from 329.58 K to 470.00 K and pressures of 40.0, 60.0 and 80.0 kPa. The thermodynamic consistency of the VLE data was evaluated using the Redlich-Kister area test, the Fredenslund test and the Van Ness point-to-point test. The data was correlated using three activity coefficient models: Wilson, NRTL and UNIQUAC. The Gibbs energy of mixing of the VLE data was analyzed to verify the suitability of the binary interaction parameters of these models. The activity coefficients and excess Gibbs free energy, calculated from the VLE experimental data and model correlation results, were analyzed to evaluate the models’ fit and the non–ideality of the binary system. The accuracy of the regression results was also assessed based on the root mean square deviation (RMSD) and average absolute deviation (AAD) for both temperature and the vapor phase mole fraction of ethyl levulinate. The results indicate that the NRTL model provided the best fit to the experimental data. Notably, the experimental data showed strong correlation with the predictions of all three models, suggesting their reliability for practical application. Full article
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18 pages, 4721 KiB  
Article
Study on Stability and Fluidity of HPMC-Modified Gangue Slurry with Industrial Validation
by Junyu Jin, Xufeng Jin, Yu Wang and Fang Qiao
Materials 2025, 18(15), 3461; https://doi.org/10.3390/ma18153461 - 23 Jul 2025
Viewed by 230
Abstract
HPMC, regulating slurry properties, is widely used in cement-based materials. Research on the application of HPMC in gangue slurry is still in its early stages. Moreover, the interactive effects of various factors on gangue slurry performance have not been thoroughly investigated. The work [...] Read more.
HPMC, regulating slurry properties, is widely used in cement-based materials. Research on the application of HPMC in gangue slurry is still in its early stages. Moreover, the interactive effects of various factors on gangue slurry performance have not been thoroughly investigated. The work examined the effects of slurry concentration (X1), maximum gangue particle size (X2), and HPMC dosage (X3) on slurry performance using response surface methodology (RSM). The microstructure of the slurry was characterized via scanning electron microscopy (SEM) and polarized light microscopy (PLM), while low-field nuclear magnetic resonance (LF-NMR) was employed to analyze water distribution. Additionally, industrial field tests were conducted. The results are presented below. (1) X1 and X3 exhibited a negative correlation with layering degree and slump flow, while X2 showed a positive correlation. Slurry concentration had the greatest impact on slurry performance, followed by maximum particle size and HPMC dosage. HPMC significantly improved slurry stability, imposing the minimum negative influence on fluidity. Interaction terms X1X2 and X1X3 significantly affected layering degree and slump flow, while X2X3 significantly affected layering degree instead of slump flow. (2) Derived from the RSM, the statistical models for layering degree and slump flow define the optimal slurry mix proportions. The gangue gradation index ranged from 0.40 to 0.428, with different gradations requiring specific slurry concentration and HPMC dosages. (3) HPMC promoted the formation of a 3D floc network structure of fine particles through adsorption-bridging effects. The spatial supporting effect of the floc network inhibited the sedimentation of coarse particles, which enhanced the stability of the slurry. Meanwhile, HPMC only converted a small amount of free water into floc water, which had a minimal impact on fluidity. HPMC addition achieved the synergistic optimization of slurry stability and fluidity. (4) Field industrial trials confirmed that HPMC-optimized gangue slurry demonstrated significant improvements in both stability and flowability. The optimized slurry achieved blockage-free pipeline transportation, with a maximum spreading radius exceeding 60 m in the goaf and a maximum single-borehole backfilling volume of 2200 m3. Full article
(This article belongs to the Section Construction and Building Materials)
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25 pages, 983 KiB  
Article
Consistency of Restricted Maximum Likelihood Estimators in High-Dimensional Kernel Linear Mixed-Effects Models with Applications in Estimating Genetic Heritability
by Xiaoxi Shen and Qing Lu
Mathematics 2025, 13(15), 2363; https://doi.org/10.3390/math13152363 - 23 Jul 2025
Viewed by 108
Abstract
Restricted maximum likelihood (REML) estimators are commonly used to obtain unbiased estimators for the variance components in linear mixed models. In modern applications, particularly in genomic studies, the dimension of the design matrix with respect to the random effects can be high. Motivated [...] Read more.
Restricted maximum likelihood (REML) estimators are commonly used to obtain unbiased estimators for the variance components in linear mixed models. In modern applications, particularly in genomic studies, the dimension of the design matrix with respect to the random effects can be high. Motivated by this, we first introduce high-dimensional kernel linear mixed models, derive the REML equations, and establish theoretical results on the consistency of REML estimators for several commonly used kernel matrices. The validity of the theories is demonstrated via simulation studies. Our results provide rigorous justification for the consistency of REML estimators in high-dimensional kernel linear mixed models and offer insights into the application of estimating genetic heritability. Finally, we apply the kernel linear mixed models to estimate genetic heritability in a real-world data application. Full article
(This article belongs to the Special Issue Statistics: Theories and Applications)
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15 pages, 2688 KiB  
Article
Recombinant Tetrameric Neuraminidase Subunit Vaccine Provides Protection Against Swine Influenza A Virus Infection in Pigs
by Ao Zhang, Bin Tan, Jiahui Wang and Shuqin Zhang
Vaccines 2025, 13(8), 783; https://doi.org/10.3390/vaccines13080783 - 23 Jul 2025
Viewed by 257
Abstract
Background/Objectives: Swine influenza A virus (swIAV), a prevalent respiratory pathogen in porcine populations, poses substantial economic losses to global livestock industries and represents a potential threat to public health security. Neuraminidase (NA) has been proposed as an important component for universal influenza [...] Read more.
Background/Objectives: Swine influenza A virus (swIAV), a prevalent respiratory pathogen in porcine populations, poses substantial economic losses to global livestock industries and represents a potential threat to public health security. Neuraminidase (NA) has been proposed as an important component for universal influenza vaccine development. NA has potential advantages as a vaccine antigen in providing cross-protection, with specific antibodies that have a broad binding capacity for heterologous viruses. In this study, we evaluated the immunogenicity and protective efficacy of a tetrameric recombinant NA subunit vaccine in a swine model. Methods: We constructed and expressed structurally stable soluble tetrameric recombinant NA (rNA) and prepared subunit vaccines by mixing with ISA 201 VG adjuvant. The protective efficacy of rNA-ISA 201 VG was compared to that of a commercial whole inactivated virus vaccine. Pigs received a prime-boost immunization (14-day interval) followed by homologous viral challenge 14 days post-boost. Results: Both rNA-ISA 201 VG and commercial vaccine stimulated robust humoral responses. Notably, the commercial vaccine group exhibited high viral-binding antibody titers but very weak NA-specific antibodies, whereas rNA-ISA 201 VG immunization elicited high NA-specific antibody titers alongside substantial viral-binding antibodies. Post-challenge, both immunization with rNA-ISA 201 VG and the commercial vaccine were effective in inhibiting viral replication, reducing viral load in porcine respiratory tissues, and effectively mitigating virus-induced histopathological damage, as compared to the PBS negative control. Conclusions: These findings found that the anti-NA immune response generated by rNA-ISA 201 VG vaccination provided protection comparable to that of a commercial inactivated vaccine that primarily induces an anti-HA response. Given that the data are derived from one pig per group, there is a requisite to increase the sample size for more in-depth validation. This work establishes a novel strategy for developing next-generation SIV subunit vaccines leveraging NA as a key immunogen. Full article
(This article belongs to the Special Issue Vaccine Development for Swine Viral Pathogens)
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22 pages, 8682 KiB  
Article
Predicting EGFRL858R/T790M/C797S Inhibitory Effect of Osimertinib Derivatives by Mixed Kernel SVM Enhanced with CLPSO
by Shaokang Li, Wenzhe Dong and Aili Qu
Pharmaceuticals 2025, 18(8), 1092; https://doi.org/10.3390/ph18081092 - 23 Jul 2025
Viewed by 156
Abstract
Background/Objectives: The resistance mutations EGFRL858R/T790M/C797S in epidermal growth factor receptor (EGFR) are key factors in the reduced efficacy of Osimertinib. Predicting the inhibitory effects of Osimertinib derivatives against these mutations is crucial for the development of more effective inhibitors. This study aims [...] Read more.
Background/Objectives: The resistance mutations EGFRL858R/T790M/C797S in epidermal growth factor receptor (EGFR) are key factors in the reduced efficacy of Osimertinib. Predicting the inhibitory effects of Osimertinib derivatives against these mutations is crucial for the development of more effective inhibitors. This study aims to predict the inhibitory effects of Osimertinib derivatives against EGFRL858R/T790M/C797S mutations. Methods: Six models were established using heuristic method (HM), random forest (RF), gene expression programming (GEP), gradient boosting decision tree (GBDT), polynomial kernel function support vector machine (SVM), and mixed kernel function SVM (MIX-SVM). The descriptors for these models were selected by the heuristic method or XGBoost. Comprehensive learning particle swarm optimizer was adopted to optimize hyperparameters. Additionally, the internal and external validation were performed by leave-one-out cross-validation (QLOO2), 5-fold cross validation (Q5fold2) and concordance correlation coefficient (CCC), QF12, and QF22. The properties of novel EGFR inhibitors were explored through molecular docking analysis. Results: The model established by MIX-SVM whose kernel function is a convex combination of three regular kernel functions is best: R2 and RMSE for training set and test set are 0.9445, 0.1659 and 0.9490, 0.1814, respectively; QLOO2, Q5fold2, CCC, QF12, and QF22 are 0.9107, 0.8621, 0.9835, 0.9689, and 0.9680. Based on these results, the IC50 values of 162 newly designed compounds were predicted using the HM model, and the top four candidates with the most favorable physicochemical properties were subsequently validated through PEA. Conclusions: The MIX-SVM method will provide useful guidance for the design and screening of novel EGFRL858R/T790M/C797S inhibitors. Full article
(This article belongs to the Special Issue QSAR and Chemoinformatics in Drug Design and Discovery)
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20 pages, 873 KiB  
Article
A Mixed Finite Volume Element Method for Nonlinear Time Fractional Fourth-Order Reaction–Diffusion Models
by Jie Zhao, Min Cao and Zhichao Fang
Fractal Fract. 2025, 9(8), 481; https://doi.org/10.3390/fractalfract9080481 - 23 Jul 2025
Viewed by 128
Abstract
In this paper, a linearized mixed finite volume element (MFVE) scheme is proposed to solve the nonlinear time fractional fourth-order reaction–diffusion models with the Riemann–Liouville time fractional derivative. By introducing an auxiliary variable σ=Δu, the original fourth-order model is [...] Read more.
In this paper, a linearized mixed finite volume element (MFVE) scheme is proposed to solve the nonlinear time fractional fourth-order reaction–diffusion models with the Riemann–Liouville time fractional derivative. By introducing an auxiliary variable σ=Δu, the original fourth-order model is reformulated into a lower-order coupled system. The first-order time derivative and the time fractional derivative are discretized by using the BDF2 formula and the weighted and shifted Grünwald difference (WSGD) formula, respectively. Then, a fully discrete MFVE scheme is constructed by using the primal and dual grids. The existence and uniqueness of a solution for the MFVE scheme are proven based on the matrix theories. The scheme’s unconditional stability is rigorously derived by using the Gronwall inequality in detail. Moreover, the optimal error estimates for u in the discrete L(L2(Ω)) and L2(H1(Ω)) norms and for σ in the discrete L2(L2(Ω)) norm are obtained. Finally, three numerical examples are given to confirm its feasibility and effectiveness. Full article
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