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19 pages, 1208 KB  
Article
Phytohormone-ROS Crosstalk Regulates Metal Transporter Expression in Sedum alfredii
by Shimiao Chen, Bin Shan, Yanyan Li, Fuhai Zheng, Xi Chen, Lilan Lv and Qinyu Lu
Toxics 2025, 13(10), 823; https://doi.org/10.3390/toxics13100823 - 26 Sep 2025
Viewed by 218
Abstract
Sedum alfredii is a cadmium (Cd) hyperaccumulator, but the regulatory mechanisms linking phytohormones and redox balance to Cd transporter expression remain unclear. In this study, we omitted external cadmium (Cd) stress to isolate and examine the interplay between phytohormone and reactive oxygen species [...] Read more.
Sedum alfredii is a cadmium (Cd) hyperaccumulator, but the regulatory mechanisms linking phytohormones and redox balance to Cd transporter expression remain unclear. In this study, we omitted external cadmium (Cd) stress to isolate and examine the interplay between phytohormone and reactive oxygen species (ROS) signaling. Exogenous treatments with abscisic acid (ABA), indole-3-acetic acid (IAA), gibberellic acid (GA3), trans-zeatin (t-Z), and H2O2 were combined with analyses of hormone levels, antioxidant enzyme activities, and transporter gene expression. Correlation and PLS-SEM analyses identified the CAT–H2O2 module as a key node: ABA and IAA enhanced CAT activity and alleviated ROS-mediated repression of transporters, while GA3 and t-Z exerted opposite effects. Functional validation using an H2O2 scavenger revealed that the regulation of HMA3 and Nramp5 by ABA and t-Z is H2O2-dependent. In contrast, IAA modulates Nramp5 through a ROS-independent pathway, while the regulatory effects of GA3 were negligible. Functional validation under Cd exposure suggests a model wherein HMA3 and Nramp5 act in a complementary manner to sequester and redistribute Cd in leaves, thereby supporting hyperaccumulation. These findings highlight hormone-specific ROS pathways as central to transporter regulation and provide mechanistic insights to improve phytoremediation efficiency. Full article
(This article belongs to the Special Issue Plant Responses to Heavy Metal)
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22 pages, 4598 KB  
Article
A ST-ConvLSTM Network for 3D Human Keypoint Localization Using MmWave Radar
by Siyuan Wei, Huadong Wang, Yi Mo and Dongping Du
Sensors 2025, 25(18), 5857; https://doi.org/10.3390/s25185857 - 19 Sep 2025
Viewed by 362
Abstract
Accurate human keypoint localization in complex environments demands robust sensing and advanced modeling. In this article, we construct a ST-ConvLSTM network for 3D human keypoint estimation via millimeter-wave radar point clouds. The ST-ConvLSTM network processes multi-channel radar image inputs, generated from multi-frame fused [...] Read more.
Accurate human keypoint localization in complex environments demands robust sensing and advanced modeling. In this article, we construct a ST-ConvLSTM network for 3D human keypoint estimation via millimeter-wave radar point clouds. The ST-ConvLSTM network processes multi-channel radar image inputs, generated from multi-frame fused point clouds through parallel pathways. These pathways are engineered to extract rich spatiotemporal features from the sequential radar data. The extracted features are then fused and fed into fully connected layers for direct regression of 3D human keypoint coordinates. In order to achieve better network performance, a mmWave radar 3D human keypoint dataset (MRHKD) is built with a hybrid human motion annotation system (HMAS), in which a binocular camera is used to measure the human keypoint coordinates and a 60 GHz 4T4R radar is used to generate radar point clouds. Experimental results demonstrate that the proposed ST-ConvLSTM, leveraging its unique ability to model temporal dependencies and spatial patterns in radar imagery, achieves MAEs of 0.1075 m, 0.0633 m, and 0.1180 m in the horizontal, vertical, and depth directions. This significant improvement underscores the model’s enhanced posture recognition accuracy and keypoint localization capability in challenging conditions. Full article
(This article belongs to the Special Issue Advances in Multichannel Radar Systems)
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30 pages, 1827 KB  
Review
The Role of Silicon Compounds in Plant Responses to Cadmium Stress: A Review
by Monika Komorowska-Trepner and Katarzyna Głowacka
Plants 2025, 14(18), 2911; https://doi.org/10.3390/plants14182911 - 19 Sep 2025
Viewed by 674
Abstract
Silicon (Si) has emerged as a promising tool for mitigating the negative effects of biotic and abiotic stresses, such as caused by heavy metals, on plants. The aim of the study was to summarize knowledge about the mechanisms underlying the interaction between silicon [...] Read more.
Silicon (Si) has emerged as a promising tool for mitigating the negative effects of biotic and abiotic stresses, such as caused by heavy metals, on plants. The aim of the study was to summarize knowledge about the mechanisms underlying the interaction between silicon and cadmium. This review first discusses silicon compounds in plant physiology, then examines mechanisms of silicon–cadmium interaction, including antioxidant defense, metal chelation, nutrient transport, molecular responses, subcellular changes, and future directions. Recent studies show that various forms of Si, such as conventional Si and Si-nanoparticles (Si NPs), can have various effects on the ability of a plant to absorb and utilize Si for protection. Silicon, taken up mainly as soluble orthosilicic acid (H4SiO4) and Si NPs, can be absorbed by plants and subsequently deposited predominantly in cell walls. It has been found that Si and Si NPs increase the activity of antioxidant enzymes, including CAT, SOD, and POD, in plants under cadmium (Cd) stress. Furthermore, Si reduces the expression of Cd transport-related genes, including OsNRAMP5 and OsHMA2 in rice. It has also been shown that supplementation with Si and Si NPs in plants under Cd stress reduces the Cd content in their tissues and changes the uptake of elements necessary for the proper functioning of the plant organism. Furthermore, Si supplementation increases the content of pectins, which are involved in the binding and neutralization of Cd. The following overview highlights the importance of both Si and SiNPs in neutralizing the harmful effects of Cd on the environment and agriculture. Full article
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24 pages, 11665 KB  
Article
Response of Nearby Sensors to Variable Doses of Nitrogen Fertilization in Winter Fodder Crops Under Mediterranean Climate
by Luís Silva, Caroline Brunelli, Raphael Moreira, Sofia Barbosa, Manuela Fernandes, Andreia Miguel, Benvindo Maçãs, Constantino Valero, Manuel Patanita, Fernando Cebola Lidon and Luís Alcino Conceição
Sensors 2025, 25(18), 5811; https://doi.org/10.3390/s25185811 - 17 Sep 2025
Viewed by 418
Abstract
The sustainable intensification of forage production in Mediterranean climates requires technological solutions that optimize the use of agricultural inputs. This study aimed to evaluate the performance of proximal optical sensors in recommending and monitoring variable rate nitrogen fertilization in winter forage crops cultivated [...] Read more.
The sustainable intensification of forage production in Mediterranean climates requires technological solutions that optimize the use of agricultural inputs. This study aimed to evaluate the performance of proximal optical sensors in recommending and monitoring variable rate nitrogen fertilization in winter forage crops cultivated under Mediterranean conditions. A handheld multispectral active sensor (HMA), a multispectral camera on an unmanned aircraft vehicle (UAV), and one passive on-the-go sensor (OTG) were used to generate real-time nitrogen (N) application prescriptions. The sensors were assessed for their correlation with agronomic parameters such as plant fresh matter (PFM), plant dry matter (PDM), plant N content (PNC), crude protein (CP) in%, crude protein yield (CPyield) per unit of area, and N uptake (NUp). The real-time N fertilization stood out by promoting a 15.23% reduction in the total N fertilizer applied compared to a usual farmer-fixed dose of 150 kg ha−1, saving 22.90 kg ha−1 without compromising crop productivity. Additionally, NDVI_OTG showed moderate simple linear correlation with PFM (R2 = 0.52), confirming its effectiveness in prescription based on vegetative vigor. UAV_II (NDVI after fertilization) showed even stronger correlations with CP (R2 = 0.58), CPyield (R2 = 0.53), and NUp (R2 = 0.53), highlighting its sensitivity to physiological responses induced by N fertilization. Although the HMA sensor operates via point readings, it also proved effective, with significant correlations to NUp (R2 = 0.55) and CPyield (R2 = 0.53). It is concluded that integrating sensors enables both precise input prescription and efficient monitoring of plant physiological responses, fostering cost-effectiveness, sustainability, and improved agronomic efficiency. Full article
(This article belongs to the Section Smart Agriculture)
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17 pages, 2473 KB  
Article
Prognostic Role of Kidney Disease in Newly Diagnosed Acute Myeloid Leukemia Under Venetoclax-Based Low-Intensity Therapy
by Katja Krüger, Razif Gabdoulline, Martin Wichmann, Bernhard M. W. Schmidt, Katharina Götze, Krischan Braitsch, Laura Schmalbrock, Lars Bullinger, Franziska Westendorf, Walter Fiedler, Anke K. Bergmann, Jürgen Krauter, Stephan Kaun, Andreas Voß, Elisabeth Koller, Ulrich Germing, Kai Wille, Martin Grießhammer, Jan Braess, Daniel Föhring, Peter Reimer, Ulrich Kaiser, Heinz Kirchen, Frank Hartmann, Jan M. Middeke, Christoph Röllig, Hartmut Döhner, Konstanze Döhner, Gernot Beutel, Felicitas R. Thol, Florian H. Heidel, Michael Heuser and Rabia Shahswaradd Show full author list remove Hide full author list
Cancers 2025, 17(18), 2993; https://doi.org/10.3390/cancers17182993 - 13 Sep 2025
Viewed by 582
Abstract
Chronic kidney disease (CKD) before treatment and renal function decline during treatment are common in elderly patients receiving hypomethylating agents (HMAs) and venetoclax (VEN). This retrospective multicenter study of 130 newly diagnosed older acute myeloid leukemia (AML) patients evaluated the prognostic impact of [...] Read more.
Chronic kidney disease (CKD) before treatment and renal function decline during treatment are common in elderly patients receiving hypomethylating agents (HMAs) and venetoclax (VEN). This retrospective multicenter study of 130 newly diagnosed older acute myeloid leukemia (AML) patients evaluated the prognostic impact of renal function before and during the first treatment cycle. A total of 56 patients (43%) had CKD, and 49 (38%) developed acute kidney injury (AKI) during treatment. AKI occurrence was associated with laboratory tumor lysis syndrome (LTLS). CKD before treatment showed a trend towards a lower overall response rate (ORR, OR 0.5, p = 0.07) in multivariable analysis (MVA) and inferior relapse-free survival (RFS, HR 2.16, p = 0.06) in univariate analysis (UVA), but not MVA (RFS, HR 1.93, p = 0.15). CKD did not affect overall survival (OS) or event-free survival (EFS). AKI during HMA/VEN therapy was associated with significantly higher 30-day and 60-day mortality rates and emerged as an independent prognostic factor for inferior OS (HR 1.86, p = 0.01) and EFS (HR 1.81, p = 0.007). RFS did not differ significantly by AKI status. Sepsis was a more frequent cause of death in patients with vs. without AKI (33% vs. 5%). In conclusion, kidney function is a key prognostic factor in HMA/VEN-treated patients, warranting further study on treatment adjustments and supportive care. Full article
(This article belongs to the Section Clinical Research of Cancer)
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26 pages, 2107 KB  
Systematic Review
Recycled Plastics in Asphalt Mixtures: A Systematic Review of Mechanical Performance, Environmental Impact and Practical Implementation
by Julio Calderón-Ramírez, David Sepúlveda-Valdez, Leonel García, Marcelo A. Lomeli-Banda, Carlos Salazar-Briones and Marco Montoya-Alcaraz
Appl. Sci. 2025, 15(18), 9901; https://doi.org/10.3390/app15189901 - 10 Sep 2025
Viewed by 1026
Abstract
The growing environmental impact of plastic waste and the high energy consumption in traditional asphalt production have driven the search for more sustainable alternatives in road construction. This systematic review evaluates the incorporation of recycled plastics into Hot Mix Asphalt (HMA) and Warm [...] Read more.
The growing environmental impact of plastic waste and the high energy consumption in traditional asphalt production have driven the search for more sustainable alternatives in road construction. This systematic review evaluates the incorporation of recycled plastics into Hot Mix Asphalt (HMA) and Warm Mix Asphalt (WMA), focusing on their effects on mechanical performance and environmental outcomes. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA/ScR) methodology, 39 studies published between 2012 and 2023 were analyzed to compare plastic types, incorporation methods (dry, wet, and pyrolysis), and dosage levels. Results show that plastics such as Polyethylene Terephthalate (PET), Low-Density Polyethylene (LDPE), and Polypropylene (PP) can improve stiffness, rutting resistance, and fatigue life. WMA technologies, while less commonly applied, offer significant environmental advantages by reducing greenhouse gas emissions and energy consumption. The review highlights the critical role of plastic type, blending method, and local conditions in optimizing performance. Overall, integrating recycled plastics into asphalt mixtures presents a promising pathway toward more durable and sustainable pavement infrastructure. Full article
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20 pages, 4144 KB  
Article
Design and Evaluation of Modified Asphalt with Enhanced Stripping Resistance Based on Surface Free Energy
by Tomohiro Fujinaga, Tomohiro Miyasaka, Yousuke Kanou and Shouichi Akiba
Constr. Mater. 2025, 5(3), 64; https://doi.org/10.3390/constrmater5030064 - 9 Sep 2025
Viewed by 383
Abstract
Latent stripping has become increasingly apparent in asphalt pavements, particularly in highway rehabilitation and international construction projects supported by Official Development Assistance (ODA) from the Government of Japan. Stripping accelerates structural deterioration, making countermeasures essential. However, in ODA projects, securing high-quality aggregates or [...] Read more.
Latent stripping has become increasingly apparent in asphalt pavements, particularly in highway rehabilitation and international construction projects supported by Official Development Assistance (ODA) from the Government of Japan. Stripping accelerates structural deterioration, making countermeasures essential. However, in ODA projects, securing high-quality aggregates or evaluating local materials is often difficult due to environmental and budgetary constraints. This study focused on Surface Free Energy (SFE) as a small-sample evaluation method and developed ten types of styrene–butadiene–styrene (SBS) polymers to enhance interfacial adhesion by targeting aggregate surface functional groups. The SFE of each Polymer-Modified Bitumen (PMB) and thirteen aggregates was measured, and the work of adhesion and moisture sensitivity index (MSI) were calculated for all combinations. Twenty-one Hot-Mix Asphalts (HMA) were then prepared and evaluated using the Hamburg Wheel Tracking Test (HWTT) based on load cycles to stripping initiation (LCSN) and to 12.5 mm rut depth (LCST). The developed PMBs showed a higher work of adhesion, a lower MSI, and substantially increased LCSN and LCST values. Strong negative correlations were observed between MSI and both HWTT indicators, confirming the utility of SFE-based MSI for material screening. This study demonstrates that interface-targeted PMBs can improve stripping resistance, thereby promoting the use of lower-quality aggregates in durable pavements. Full article
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18 pages, 2338 KB  
Article
Hierarchical Multiattention Temporal Fusion Network for Dual-Task Atrial Fibrillation Subtyping and Early Risk Prediction
by Liang-Hung Wang, Jia-Wen Wang, Chao-Xin Xie, Zne-Jung Lee, Bing-Jie Cai, Tsung-Yi Chen, Shih-Lun Chen, Chiung-An Chen, Patricia Angela R. Abu and Tao Yang
Mathematics 2025, 13(17), 2872; https://doi.org/10.3390/math13172872 - 5 Sep 2025
Viewed by 570
Abstract
Atrial fibrillation (AF) is a common arrhythmia associated with major adverse cardiovascular events. Early detection and short-horizon risk prediction are therefore clinically critical. Prior attention-based electrocardiogram (ECG) models typically treated subtype classification and short-horizon onset risk prediction as separate tasks and optimized attention [...] Read more.
Atrial fibrillation (AF) is a common arrhythmia associated with major adverse cardiovascular events. Early detection and short-horizon risk prediction are therefore clinically critical. Prior attention-based electrocardiogram (ECG) models typically treated subtype classification and short-horizon onset risk prediction as separate tasks and optimized attention in only one representational dimension rather than in a coordinated hierarchy. We propose a hierarchical multiattention temporal fusion network (HMA-TFN). The proposed framework jointly integrates lead-level, morphology-level, and rhythm-level attention, enabling the model to simultaneously highlight diagnostically informative leads, capture waveform abnormalities, and characterize long-range temporal dependencies. Moreover, the model is trained for dual tasks—AF subtype classification and 30-min onset prediction. Experiments were conducted on three open-source databases and the Fuzhou University–Fujian Provincial Hospital (FZU-FPH) clinical database, comprising thousands of dual-lead ECG recordings from a diverse subject population. Experimental results show that HMA-TFN achieves 95.77% accuracy in classifying paroxysmal AF (PAAF) and persistent AF (PEAF), and 96.36% accuracy in predicting PAAF occurrence 30 min in advance. Ablations show monotonic gains as each attention level is added, delivering 14.0% accuracy over the baseline for subtyping and 5.2% for prediction. Grad-CAM visualization highlights clinically relevant features such as absent P-waves, confirming model interpretability. On the FZU-FPH clinical database, it achieves a generalization performance of 94.31%, demonstrating its strong potential for clinical application. Full article
(This article belongs to the Section E: Applied Mathematics)
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20 pages, 2126 KB  
Article
Genomics-Assisted Improvement in Blast Resistance and Low Cadmium Accumulation in an Elite Rice Variety
by Zhi Xu, Zhizhou He, Yanglan He, Hailong Chen, Jihua Cheng, Changrong Ye, Zhouwei Li, Le Li, Hexing Yin, Lijia Zheng, Yuntian Wu, Bingchuan Tian and Junhua Peng
Agronomy 2025, 15(9), 2130; https://doi.org/10.3390/agronomy15092130 - 5 Sep 2025
Viewed by 487
Abstract
Xiangwanxian 13 (XWX13), an elite fragrant indica rice, is highly susceptible to rice blast and accumulates cadmium (Cd) in grain above the food safety limit in Cd-contaminated paddies, severely constraining its commercial use. Despite these shortcomings, the variety is widely grown for its [...] Read more.
Xiangwanxian 13 (XWX13), an elite fragrant indica rice, is highly susceptible to rice blast and accumulates cadmium (Cd) in grain above the food safety limit in Cd-contaminated paddies, severely constraining its commercial use. Despite these shortcomings, the variety is widely grown for its high yield and superior grain quality. To overcome these limitations, we conducted marker-assisted backcrossing (MABC) complemented by genome-wide background selection. Four major genes, namely Pi1, Pi2, OsHMA3, and OsNramp5, were precisely introduced into XWX13. Two preferable BC3MF5 improved lines iXWX13-1 (stacking Pi1 + Pi2 + OsHMA3) and iXWX13-2 (stacking Pi1 + Pi2 + OsNramp5) were obtained with genomic background recovery rates of 94.44% and 94.63%, evaluated by using the RICE 1K SNP array, respectively. Seedling resistance spectrum assays demonstrated more than a 97% blast resistance rate against 39 Magnaporthe oryzae isolates, and both lines showed enhanced leaf and panicle neck blast resistance in natural nurseries. Multi-site field trials revealed grain Cd concentrations of 0.009–0.077 mg kg−1 in iXWX13-2, 90.98–98.87% lower than those in XWX13. Importantly, yield, major agronomic traits, and grain quality remained indistinguishable from the original variety. This study provides the first demonstration that MABC coupled with SNP array background selection can simultaneously enhance blast resistance and reduce grain Cd in XWX13 without yield or quality penalties, offering a robust strategy for pyramiding multiple desirable genes into elite cultivars. Full article
(This article belongs to the Section Crop Breeding and Genetics)
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16 pages, 1196 KB  
Article
Rapid On-Field Monitoring for Odor-Active Homologous Aliphatic Aldehydes and Ketones from Hot-Mix Asphalt Emission via Dynamic-SPME Air Sampling with Online Gas Chromatographic Analysis
by Stefano Dugheri, Giovanni Cappelli, Ilaria Rapi, Riccardo Gori, Lorenzo Venturini, Niccolò Fanfani, Chiara Vita, Fabio Cioni, Ettore Guerriero, Domenico Cipriano, Gian Luca Bartolucci, Luca Di Giampaolo, Mieczyslaw Sajewicz, Veronica Traversini, Nicola Mucci and Antonio Baldassarre
Molecules 2025, 30(17), 3545; https://doi.org/10.3390/molecules30173545 - 29 Aug 2025
Viewed by 608
Abstract
Odorous emissions from hot-mix asphalt (HMA) plants are a growing environmental concern, particularly due to airborne aldehydes and ketones, which have low odor thresholds and a strong sensory impact. This study presents a field-ready analytical method for monitoring odor-active volatile compounds. The system [...] Read more.
Odorous emissions from hot-mix asphalt (HMA) plants are a growing environmental concern, particularly due to airborne aldehydes and ketones, which have low odor thresholds and a strong sensory impact. This study presents a field-ready analytical method for monitoring odor-active volatile compounds. The system uses dynamic solid-phase microextraction (SPME and SPME Arrow) with on-fiber derivatization via O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) and is coupled to gas chromatography–mass spectrometry (GC–MS) for direct detection. A flow-cell sampling unit enables the real-time capture of aliphatic aldehydes and ketones under transient emission conditions. Calibration using permeation tubes demonstrated sensitivity (limits of detection (LODs) below 0.13 μg/m3), recovery above 85% and consistent reproducibility. Compound identity was confirmed using retention indices and fragmentation patterns. Uncertainty assessment followed ISO GUM (Guide to the Expression of Uncertainty in Measurement) standards, thereby validating the method’s environmental applicability. Field deployment 200 m from an HMA facility identified measurable concentrations that aligned with CALPUFF model predictions. The method’s dual-isomer resolution and 10 min runtime make it ideal for responding to time-sensitive odor complaints. Overall, this approach supports regulatory efforts by enabling high-throughput on-site chemical monitoring and improving source attribution in cases of odor nuisance. Full article
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18 pages, 5845 KB  
Article
Mechanical Properties and Microstructure of High-Performance Cold Mix Asphalt Modified with Portland Cement
by Anmar Dulaimi, Yasir N. Kadhim, Qassim Ali Al Quraishy, Hayder Al Hawesah, Tiago Pinto Ribeiro and Luís Filipe Almeida Bernardo
CivilEng 2025, 6(3), 46; https://doi.org/10.3390/civileng6030046 - 27 Aug 2025
Viewed by 814
Abstract
The use of hot mix asphalt (HMA) has several drawbacks, such as the emission of harmful gases into the atmosphere, difficulties in maintaining temperature over long distances, and the requirement for high energy consumption during preparation and installation. In order to solve these [...] Read more.
The use of hot mix asphalt (HMA) has several drawbacks, such as the emission of harmful gases into the atmosphere, difficulties in maintaining temperature over long distances, and the requirement for high energy consumption during preparation and installation. In order to solve these issues, this research aimed to produce High-Performance Cold Mix Asphalt (HP-CMA), in which Ordinary Portland Cement (OPC) is used as a filler to replace limestone filler at 0%, 1.5%, 3%, 4.5%, and 6% of the aggregate weight. Indirect Tensile Stiffness Modulus (ITSM), moisture susceptibility, temperature susceptibility, and microstructural analysis tests were carried out. The results showed that the ITSM was considerably enhanced when OPC was utilized. When comparing HP-CMA with 3% OPC to the control HMA (100–150 pen), the ITSM increased by approximately 80% after three days. In contrast, HP-CMA with 4.5% OPC achieved the same ITSM as the control HMA (40–60 pen) after seven days. Moreover, the ITSM of the HMA 40–60 pen decreased by 91.93% when the temperature rose from 20 °C to 45 °C, whereas the ITSM of the HP-CMA with 6% OPC decreased by 42.47% over the same temperature range. This suggests that HP-CMA is more stable than the HMA 40–60 pen at elevated temperatures. The superior performance of the HP-CMA can be attributed to two essential factors: the improved binding effect due to the demulsification of the asphalt emulsion used as a binder, and the formation of hydration products from the added cement. Full article
(This article belongs to the Section Construction and Material Engineering)
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18 pages, 1572 KB  
Article
Prognostic Impact of the AML60+ Score for Elderly Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents: A Retrospective Multicentric Analysis
by Verena Petermichl, Stefan Fuchs, Matthias Weber, Katrin Gobat, Charlotte Micheloud, Lukas Graf, Yannick Gerth, Jeroen S. Goede, Thomas Lehmann, Christoph Driessen, Ulrich J. M. Mey, Richard Cathomas, Sergio Cogliatti and Tobias Silzle
Cancers 2025, 17(16), 2658; https://doi.org/10.3390/cancers17162658 - 14 Aug 2025
Viewed by 664
Abstract
Background: The AML60+ score has been proposed for risk stratification in intensively treated elderly patients with acute myeloid leukemia (AML) or high-risk myelodysplastic neoplasms (MDS). Its prognostic impact in patients treated with hypomethylating agents (HMA) is unknown. Methods: Patients ≥ 60 years of [...] Read more.
Background: The AML60+ score has been proposed for risk stratification in intensively treated elderly patients with acute myeloid leukemia (AML) or high-risk myelodysplastic neoplasms (MDS). Its prognostic impact in patients treated with hypomethylating agents (HMA) is unknown. Methods: Patients ≥ 60 years of age diagnosed with AML or MDS/AML according to ICC2022 were eligible for this retrospective and multicenter chart review if they had received at least one cycle of HMA-based treatment. Results: A cohort of 142 patients was analyzed. During follow-up (median 8 months), 114 patients died. The molecular Prognostic Score (mPRS) was available for 121 patients, the European Leukemia Net (ELN) 2022 classification for 117 patients, and the AML60+ for 105 patients. According to AML60+, 33 patients (31.4%) were classified as very poor risk, 36 (34.3%) as poor risk, and 34 (32.4%) as intermediate risk. Two patients (1.9%) were classified as favorable. Median overall survival (OS) was 21.7 months (mo) for the combined intermediate/favorable group, 7 mo for the poor risk group and 3 mo for the very poor risk group (p < 0.0001). Cox regression analysis (reference category: very poor) showed a significantly lower risk of death for both intermediate/favorable risk patients (HR 0.17, 95% CI 0.10–0.31, p < 0.001) and poor risk patients (HR 0.47, 95% CI 0.28–0.78, p = 0.004). The concordance score was 0.67 for AML60+, 0.60 for mPRS, and 0.58 for ELN2022. Conclusions: The AML60+ may represent a useful prognostic tool for elderly AML patients treated with HMA-based therapies. In particular, it could help to identify a group with a relatively favorable prognosis that is not clearly identified by the ELN2022 or the mPRS risk classification. However, analyses of larger cohorts are necessary to confirm our findings. Full article
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19 pages, 684 KB  
Article
Does the Timing of Response Impact the Outcome of Relapsed/Refractory Acute Myeloid Leukemia Treated with Venetoclax in Combination with Hypomethylating Agents? A Proof of Concept from a Monocentric Observational Study
by Ermelinda Longo, Fanny Erika Palumbo, Andrea Duminuco, Laura Longo, Daniela Cristina Vitale, Serena Brancati, Cinzia Maugeri, Marina Silvia Parisi, Giuseppe Alberto Palumbo, Giovanni Luca Romano, Filippo Drago, Francesco Di Raimondo, Lucia Gozzo and Calogero Vetro
J. Clin. Med. 2025, 14(15), 5586; https://doi.org/10.3390/jcm14155586 - 7 Aug 2025
Viewed by 760
Abstract
Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing [...] Read more.
Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article
(This article belongs to the Section Hematology)
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13 pages, 1636 KB  
Article
Mechanical Performance of Sustainable Asphalt Mixtures Incorporating RAP and Panasqueira Mine Waste
by Hernan Patricio Moyano-Ayala and Marisa Sofia Fernandes Dinis-Almeida
Constr. Mater. 2025, 5(3), 52; https://doi.org/10.3390/constrmater5030052 - 4 Aug 2025
Viewed by 562
Abstract
The increasing demand for sustainable practices in road construction has prompted the search for environmentally friendly and cost-effective materials. This study explores the incorporation of reclaimed asphalt pavement (RAP) and Panasqueira mine waste (greywacke aggregates) as full replacements for virgin aggregates in hot [...] Read more.
The increasing demand for sustainable practices in road construction has prompted the search for environmentally friendly and cost-effective materials. This study explores the incorporation of reclaimed asphalt pavement (RAP) and Panasqueira mine waste (greywacke aggregates) as full replacements for virgin aggregates in hot mix asphalt (HMA), aligning with the objectives of UN Sustainable Development Goal 9. Three asphalt mixtures were prepared: a reference mixture (MR) with granite aggregates, and two modified mixtures (M15 and M20) with 15% and 20% RAP, respectively. All mixtures were evaluated through Marshall stability, stiffness modulus, water sensitivity, and wheel tracking tests. The results demonstrated that mixtures containing RAP and mine waste met Portuguese specifications for surface courses. Specifically, the M20 mixture showed the highest stiffness modulus, improved moisture resistance, and the best performance against permanent deformation. These improvements are attributed to the presence of stiff aged binder in RAP and the mechanical characteristics of the greywacke aggregates. Overall, the findings confirm that the combined use of RAP and mining waste provides a technically viable and sustainable alternative for asphalt pavement construction, contributing to resource efficiency and circular economy goals. Full article
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Article
Transcriptome Analysis Reveals Candidate Pathways and Genes Involved in Wheat (Triticum aestivum L.) Response to Zinc Deficiency
by Shoujing Zhu, Shiqi Zhang, Wen Wang, Nengbing Hu and Wenjuan Shi
Biology 2025, 14(8), 985; https://doi.org/10.3390/biology14080985 - 2 Aug 2025
Viewed by 724
Abstract
Zinc (Zn) deficiency poses a major global health challenge, and wheat grains generally contain low Zn concentrations. In this study, the wheat cultivar ‘Zhongmai 175’ was identified as zinc-efficient. Hydroponic experiments demonstrated that Zn deficiency induced the secretion of oxalic acid and malic [...] Read more.
Zinc (Zn) deficiency poses a major global health challenge, and wheat grains generally contain low Zn concentrations. In this study, the wheat cultivar ‘Zhongmai 175’ was identified as zinc-efficient. Hydroponic experiments demonstrated that Zn deficiency induced the secretion of oxalic acid and malic acid in root exudates and significantly increased total root length in ‘Zhongmai 175’. To elucidate the underlying regulatory mechanisms, transcriptome profiling via RNA sequencing was conducted under Zn-deficient conditions. A total of 2287 and 1935 differentially expressed genes (DEGs) were identified in roots and shoots, respectively. Gene Ontology enrichment analysis revealed that these DEGs were primarily associated with Zn ion transport, homeostasis, transmembrane transport, and hormone signaling. Key DEGs belonged to gene families including VIT, NAS, DMAS, ZIP, tDT, HMA, and NAAT. KEGG pathway analysis indicated that phenylpropanoid biosynthesis, particularly lignin synthesis genes, was significantly downregulated in Zn-deficient roots. In shoots, cysteine and methionine metabolism, along with plant hormone signal transduction, were the most enriched pathways. Notably, most DEGs in shoots were associated with the biosynthesis of phytosiderophores (MAs, NA) and ethylene. Overall, genes involved in Zn ion transport, phytosiderophore biosynthesis, dicarboxylate transport, and ethylene biosynthesis appear to play central roles in wheat’s adaptive response to Zn deficiency. These findings provide a valuable foundation for understanding the molecular basis of Zn efficiency in wheat and for breeding Zn-enriched varieties. Full article
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