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25 pages, 947 KB  
Systematic Review
Systematic Review of Biomass Supercritical Water Gasification for Energy Production
by Filipe Neves, Armando A. Soares and Abel Rouboa
Energies 2025, 18(20), 5374; https://doi.org/10.3390/en18205374 (registering DOI) - 12 Oct 2025
Abstract
Due to the growing global population, rising energy demands, and the environmental impacts of fossil fuel use, there is an urgent need for sustainable energy sources. Biomass conversion technologies have emerged as a promising solution, particularly supercritical water gasification (SCWG), which enables efficient [...] Read more.
Due to the growing global population, rising energy demands, and the environmental impacts of fossil fuel use, there is an urgent need for sustainable energy sources. Biomass conversion technologies have emerged as a promising solution, particularly supercritical water gasification (SCWG), which enables efficient energy recovery from wet and dry biomass. This systematic review, following PRISMA 2020 guidelines, analyzed 51 peer-reviewed studies published between 2015 and 2025. The number of publications has increased over the decade, reflecting rising interest in SCWG for energy production. Research has focused on six biomass feedstock categories, with lignocellulosic and wet biomasses most widely studied. Reported energy efficiencies ranged from ~20% to >80%, strongly influenced by operating conditions and system integration. Integrating SCWG with solid oxide fuel cells, organic Rankine cycles, carbon capture and storage, or solar input enhanced both energy recovery and environmental performance. While SCWG demonstrates lower greenhouse gas emissions than conventional methods, many studies lacked comprehensive life cycle or economic analyses. Common limitations include high energy demand, modeling simplifications, and scalability challenges. These trends highlight both the potential and the barriers to advancing SCWG as a viable biomass-to-energy technology. Full article
27 pages, 4875 KB  
Review
Toward Modern Pesticide Use Reduction Strategies in Advancing Precision Agriculture: A Bibliometric Review
by Sebastian Lupica, Salvatore Privitera, Antonio Trusso Sfrazzetto, Emanuele Cerruto and Giuseppe Manetto
AgriEngineering 2025, 7(10), 346; https://doi.org/10.3390/agriengineering7100346 (registering DOI) - 12 Oct 2025
Abstract
Precision agriculture technologies (PATs) are revolutionizing the agricultural sector by minimizing the reliance on plant protection products (PPPs) in crop management. This approach integrates a broad range of advanced solutions employed to help farmers in optimizing PPP application, while minimizing input and maintaining [...] Read more.
Precision agriculture technologies (PATs) are revolutionizing the agricultural sector by minimizing the reliance on plant protection products (PPPs) in crop management. This approach integrates a broad range of advanced solutions employed to help farmers in optimizing PPP application, while minimizing input and maintaining effective crop protection. These technologies include sensors, drones, robotics, variable rate systems, and artificial intelligence (AI) tools that support site-specific pesticide applications. The objective of this review was to perform a bibliometric analysis to identify scientific trends and gaps in this field. The analysis was conducted using Scopus and Web of Science databases for the period of 2015–2024, by applying a data filtering process to ensure a clean and reliable dataset. The methodology involved citation, co-authorship, co-citation, and co-occurrence analysis. VOSviewer software (version 1.6.20) was used to generate maps and assess global research developments. Results identified AI, sensor, and data processing categories as the most central and interconnected scientific topics, emphasizing their vital role in the evolution of precision spraying technology. Bibliometric analysis highlighted that China, the United States, and India were the most productive countries, with strong collaborations within Europe. The co-occurrence and co-citation analyses revealed increasing interdisciplinarity and the integration of AI tools across various technologies. These findings help identify key experts and research leaders in the precision agriculture domain, thus underscoring the shift toward a more sustainable, data-driven, and synergistic approach in crop protection. Full article
(This article belongs to the Collection Research Progress of Agricultural Machinery Testing)
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36 pages, 4822 KB  
Review
Converting Wastewater Sludge into Slow-Release Fertilizers via Biochar and Encapsulation Technologies
by Babar Azeem
Appl. Sci. 2025, 15(20), 10954; https://doi.org/10.3390/app152010954 (registering DOI) - 12 Oct 2025
Abstract
The rising demand for sustainable agriculture and circular resource management has intensified interest in converting wastewater sludge into value-added products. This review explores the transformation of sewage sludge into slow- and controlled-release fertilizers (CRFs), with a focus on biochar production and encapsulation technologies. [...] Read more.
The rising demand for sustainable agriculture and circular resource management has intensified interest in converting wastewater sludge into value-added products. This review explores the transformation of sewage sludge into slow- and controlled-release fertilizers (CRFs), with a focus on biochar production and encapsulation technologies. Sewage sludge is rich in essential macronutrients (N, P, K), micronutrients, and organic matter, making it a promising feedstock for agricultural applications. However, its use is constrained by challenges including compositional variability, presence of heavy metals, pathogens, and emerging contaminants such as microplastics and PFAS (Per- and Polyfluoroalkyl Substances). The manuscript discusses a range of stabilization and conversion techniques, such as composting, anaerobic digestion, pyrolysis, hydrothermal carbonization, and nutrient recovery from incinerated sludge ash. Special emphasis is placed on coating and encapsulation technologies that regulate nutrient release, improve fertilizer efficiency, and reduce environmental losses. The role of natural, synthetic, and biodegradable polymers in enhancing release mechanisms is analyzed in the context of agricultural performance and soil health. While these technologies offer environmental and agronomic benefits, large-scale adoption is hindered by technical, economic, and regulatory barriers. The review highlights key challenges and outlines future perspectives, including the need for advanced coating materials, improved contaminant mitigation strategies, harmonized regulations, and field-scale validation of CRFs. Overall, the valorisation of sewage sludge into CRFs presents a viable strategy for nutrient recovery, waste minimization, and sustainable food production. With continued innovation and policy support, sludge-based fertilizers can become a critical component of the green transition in agriculture. Full article
(This article belongs to the Section Green Sustainable Science and Technology)
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24 pages, 943 KB  
Review
A Review on AI Miniaturization: Trends and Challenges
by Bin Tang, Shengzhi Du and Antonie Johan Smith
Appl. Sci. 2025, 15(20), 10958; https://doi.org/10.3390/app152010958 (registering DOI) - 12 Oct 2025
Abstract
Artificial intelligence (AI) often suffers from high energy consumption and complex deployment in resource-constrained environments, leading to a structural mismatch between capability and deployability. This review takes two representative scenarios—energy-first and performance-first—as the main thread, systematically comparing cloud, edge, and fog/cloudlet/mobile edge computing [...] Read more.
Artificial intelligence (AI) often suffers from high energy consumption and complex deployment in resource-constrained environments, leading to a structural mismatch between capability and deployability. This review takes two representative scenarios—energy-first and performance-first—as the main thread, systematically comparing cloud, edge, and fog/cloudlet/mobile edge computing (MEC)/micro data center (MDC) architectures. Based on a standardized literature search and screening process, three categories of miniaturization strategies are distilled: redundancy compression (e.g., pruning, quantization, and distillation), knowledge transfer (e.g., distillation and parameter-efficient fine-tuning), and hardware–software co-design (e.g., neural architecture search (NAS), compiler-level, and operator-level optimization). The purposes of this review are threefold: (1) to unify the “architecture–strategy–implementation pathway” from a system-level perspective; (2) to establish technology–budget mapping with verifiable quantitative indicators; and (3) to summarize representative pathways for energy- and performance-prioritized scenarios, while highlighting current deficiencies in data disclosure and device-side validation. The findings indicate that, compared with single techniques, cross-layer combined optimization better balances accuracy, latency, and power consumption. Therefore, AI miniaturization should be regarded as a proactive method of structural reconfiguration for large-scale deployment. Future efforts should advance cross-scenario empirical validation and standardized benchmarking, while reinforcing hardware–software co-design. Compared with existing reviews that mostly focus on a single dimension, this review proposes a cross-level framework and design checklist, systematizing scattered optimization methods into reusable engineering pathways. Full article
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26 pages, 8555 KB  
Review
Microbial Production of N-Acetylneuraminic Acid Using Metabolically Engineered Escherichia coli and Bacillus subtilis: Advances and Perspectives
by Jingru Dang, Zhijie Shi, Heyun Wu, Qian Ma and Xixian Xie
Foods 2025, 14(20), 3478; https://doi.org/10.3390/foods14203478 (registering DOI) - 12 Oct 2025
Abstract
N-Acetylneuraminic acid (Neu5Ac), the predominant form of sialic acids (Sias), is extensively utilized in the food, pharmaceutical, and cosmetic industries. Microbial fermentation serves as a critical production method for its economical, eco-friendly, and scalable production. Escherichia coli and Bacillus subtilis, as [...] Read more.
N-Acetylneuraminic acid (Neu5Ac), the predominant form of sialic acids (Sias), is extensively utilized in the food, pharmaceutical, and cosmetic industries. Microbial fermentation serves as a critical production method for its economical, eco-friendly, and scalable production. Escherichia coli and Bacillus subtilis, as primary industrial workhorses for Neu5Ac production, have been extensively investigated owing to their well-characterized genetic frameworks and mature molecular toolkits. Nevertheless, the intricate regulatory networks inherent to microbial systems present formidable obstacles to the high-efficiency biosynthesis of Neu5Ac. This review delineates the genetic and molecular mechanisms underlying Neu5Ac biosynthesis in both E. coli and B. subtilis. Furthermore, the rational and irrational strategies for constructing Neu5Ac microbial cell factories are systematically summarized, including the application of rational metabolic engineering to relieve feedback regulation, reconfigure metabolic networks, implement dynamic regulation, and optimize carbon sources; as well as the use of irrational strategies including directed evolution of key enzymes and high-throughput screening based on biosensors. Finally, this review addresses current challenges in Neu5Ac bioproduction and proposes integrative solutions combining machine learning with systems metabolic engineering to advance the construction of high-titer Neu5Ac microbial cell factory and the refinement of advanced fermentation technologies. Full article
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15 pages, 2984 KB  
Article
Rational Design of Cu@Pd Core–Shell Nanostructures via Galvanic Replacement for Dual Electrochemical Applications: Hydrogen Evolution and Nitrate Reduction Reactions
by Bommireddy Naveen and Sang-Wha Lee
Molecules 2025, 30(20), 4062; https://doi.org/10.3390/molecules30204062 (registering DOI) - 12 Oct 2025
Abstract
Developing bifunctional electrocatalysts that simultaneously enable green hydrogen production and water purification is essential for advancing sustainable energy and environmental technologies. In this study, we present Cu@Pd core–shell nanostructures fabricated through template-assisted electrodeposition of Cu, followed by galvanic Pd modification on pyrolytic graphite [...] Read more.
Developing bifunctional electrocatalysts that simultaneously enable green hydrogen production and water purification is essential for advancing sustainable energy and environmental technologies. In this study, we present Cu@Pd core–shell nanostructures fabricated through template-assisted electrodeposition of Cu, followed by galvanic Pd modification on pyrolytic graphite electrodes (PGEs). The optimised catalyst exhibited superior hydrogen evolution reaction (HER) activity, with an onset potential of 70 mV, a low Tafel slope of 33 mV dec−1 and excellent stability during prolonged HER operation. In addition to hydrogen evolution, Cu@Pd/PGE shows significantly enhanced nitrate reduction reaction (NRR) activity compared to Cu/PGE in both alkaline and neutral conditions. Under ideal conditions, the catalyst achieved 60% nitrate removal with high selectivity towards ammonia and minimal nitrite formation, emphasising its superior performance. This enhanced bifunctionality arises from the synergistic Cu–Pd interface, facilitating efficient nitrate adsorption and selective hydrogenation. Despite their high catalytic activity for both HER and NRR, the Cu@Pd nanostructures could often emerge as a versatile platform for integration into sustainable hydrogen production and an effective denitrification process. Full article
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17 pages, 3460 KB  
Article
Integrating Pumped Hydro Storage into Zero Discharge Strategy for Wastewater: The Alicante Case Study
by Miguel Ángel Bofill, Francisco-Javier Sánchez-Romero, Francisco Zapata-Raboso, Helena M. Ramos and Modesto Pérez-Sánchez
Appl. Sci. 2025, 15(20), 10953; https://doi.org/10.3390/app152010953 (registering DOI) - 12 Oct 2025
Abstract
The use of reclaimed water is crucial to prevent pollution from wastewater discharges and mitigate the water deficit faced by irrigation districts or other non-potable water users. Therefore, the zero-discharge strategy represents a significant challenge for coastal cities affected by marine pollution from [...] Read more.
The use of reclaimed water is crucial to prevent pollution from wastewater discharges and mitigate the water deficit faced by irrigation districts or other non-potable water users. Therefore, the zero-discharge strategy represents a significant challenge for coastal cities affected by marine pollution from effluents. In regions such as the Mediterranean arc, agricultural areas located near these cities are increasingly exposed to reduced water allocations or rising irrigation demands due to the impacts of climate change. To address this dual challenge, a circular system is proposed through the implementation of hybrid treatment technologies that enable zero wastewater discharge into the sea. This approach would contribute up to 30 hm3 of reclaimed water annually for irrigation, covering approximately 27,000 hectares of cropland in the province of Alicante. The proposed system integrates advanced techniques, such as reverse osmosis, to ensure irrigation water quality, while also considering partial blending strategies to optimize resource use. Additionally, constructed wetlands are incorporated to regulate and treat the reject streams produced by these processes, minimizing their environmental impact. This combined strategy enhances water reuse efficiency, strengthens agricultural resilience, and provides a sustainable model for managing water resources in coastal Mediterranean regions. Full article
(This article belongs to the Special Issue Water Pollution and Wastewater Treatment Chemistry)
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33 pages, 1449 KB  
Review
Rare Earth Elements: A Review of Primary Sources, Applications, Business Investment, and Characterization Techniques
by Fabiano Ferreira de Medeiros, Alexandre Pereira Wentz, Beatriz Almeida Santos Castro, Fabricio Dias Rodrigues, Sara Silva Alves, Maria das Graças Andrade Korn, Jefferson Bettini, Jeancarlo Pereira dos Anjos and Lílian Lefol Nani Guarieiro
Appl. Sci. 2025, 15(20), 10949; https://doi.org/10.3390/app152010949 (registering DOI) - 12 Oct 2025
Abstract
Minerals bearing rare earth elements (REEs) are formed through long geological processes, among which monazite, bastnasite, xenotime, and ionic adsorption clays are the most economically exploited. Although Brazil has one of the largest reserves of REEs on the planet, its production is still [...] Read more.
Minerals bearing rare earth elements (REEs) are formed through long geological processes, among which monazite, bastnasite, xenotime, and ionic adsorption clays are the most economically exploited. Although Brazil has one of the largest reserves of REEs on the planet, its production is still not significant on the world stage. China remains dominant, with the largest reserves of REEs and controlling more than half of world production. Due to their important application in advanced clean and low-carbon energy technologies, REEs have become fundamental to the energy transition process. Technological applications related to catalyst synthesis, ceramics production, and metallurgy have been explored. Furthermore, the use of REEs in devices of great demand today, such as computer memory, rechargeable batteries, and mobile phones, has been cited. With the growing demand for these critical minerals, large mining companies are seeking to implement cleaner production policies in their processes and save natural resources to minimize the environmental impacts of the exploration. Robust analytical techniques have made it possible to characterize these elements in multi-element geological matrices, with the increasing exploration and identification of new REE mineral reserves. Full article
(This article belongs to the Special Issue Recent Advances in Prospecting Geology)
25 pages, 14721 KB  
Review
Biomass-Derived Hard Carbon Anodes for Sodium-Ion Batteries: Recent Advances in Synthesis Strategies
by Narasimharao Kitchamsetti, Kyoung-ho Kim, HyukSu Han and Sungwook Mhin
Nanomaterials 2025, 15(20), 1554; https://doi.org/10.3390/nano15201554 (registering DOI) - 12 Oct 2025
Abstract
Biomass-derived hard carbon (BHC) has attracted considerable attention as a sustainable and cost-effective anode material for sodium-ion batteries (SIBs), owing to its natural abundance, environmental friendliness, and promising electrochemical performance. This review provides a detailed overview of recent progress in the synthesis, structural [...] Read more.
Biomass-derived hard carbon (BHC) has attracted considerable attention as a sustainable and cost-effective anode material for sodium-ion batteries (SIBs), owing to its natural abundance, environmental friendliness, and promising electrochemical performance. This review provides a detailed overview of recent progress in the synthesis, structural design, and performance optimization of BHC materials. It encompasses key fabrication routes, such as high-temperature pyrolysis, hydrothermal pretreatment, chemical and physical activation, heteroatom doping, and templating techniques, that have been employed to control pore architecture, defect density, and interlayer spacing. Among these strategies, activation-assisted pyrolysis and heteroatom doping have shown the most significant improvements in sodium (Na) storage capacity and long-term cycling stability. The review further explores the correlations between microstructure and electrochemical behavior, outlines the main challenges limiting large-scale application, and proposes future research directions toward scalable production and integration of BHC anodes in practical SIB systems. Overall, these advancements highlight the strong potential of BHC as a next-generation anode for grid-level and renewable energy storage technologies. Full article
(This article belongs to the Section Energy and Catalysis)
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15 pages, 8493 KB  
Article
Phase-Retrieval Algorithm for Hololens Resolution Analysis in a Sustainable Photopolymer
by Tomás Lloret, Víctor Navarro-Fuster, Marta Morales-Vidal and Inmaculada Pascual
Polymers 2025, 17(20), 2732; https://doi.org/10.3390/polym17202732 (registering DOI) - 11 Oct 2025
Abstract
In this paper, the iterative Gerchberg–Saxton (GS) phase-retrieval algorithm is employed to reconstruct the amplitude spread function (ASF) of hololenses (HLs) recorded on a sustainable PVA/acrylate-based photopolymer, Biophotopol, when working with a CCD sensor. The main objective of this work is [...] Read more.
In this paper, the iterative Gerchberg–Saxton (GS) phase-retrieval algorithm is employed to reconstruct the amplitude spread function (ASF) of hololenses (HLs) recorded on a sustainable PVA/acrylate-based photopolymer, Biophotopol, when working with a CCD sensor. The main objective of this work is to characterize the spatial resolution of HLs, which are key components in a wide range of optical systems, including augmented reality (AR) glasses, combined information displays, and holographic solar concentrators. The GS algorithm, known for its efficiency in phase retrieval without prior knowledge of the phase of the optical system, is used to reconstruct the ASF, which is critical for mitigating information loss during imaging. Spatial resolution is quantified by convolving the ASFs obtained with two resolution tests (objective and subjective) and analyzing the resulting image using a CCD sensor. The convolution process allows an accurate assessment of lens performance, highlighting the resolution limits of manufactured lenses. The results show that the iterative GS algorithm provides a reliable method to improve image quality by recovering phase and amplitude information that might otherwise be lost, especially when using CCD or CMOS sensors. In addition, the recorded hololenses exhibit a spatial resolution of 8.9 lp/mm when evaluated with the objective Siemens star chart, and 30 cycles/degree when evaluated with the subjective Random E visual acuity test, underscoring the ability of Biophotopol-based HLs to meet the performance requirements of advanced optical applications. This work contributes to the development of sustainable high-resolution holographic lenses for modern imaging technologies, offering a promising alternative for future optical systems. Full article
(This article belongs to the Special Issue Advances in Photopolymer Materials: Holographic Applications)
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20 pages, 966 KB  
Review
Unraveling the Genome Diversity of Leishmania Parasites Using Next-Generation DNA Sequencing Strategies
by Alejandro Llanes, Carlos M. Restrepo and Ricardo Lleonart
Life 2025, 15(10), 1590; https://doi.org/10.3390/life15101590 (registering DOI) - 11 Oct 2025
Abstract
Parasites of the Leishmania genus are globally distributed and cause various clinical presentations in animals and humans, collectively known as leishmaniasis. The genomes of Leishmania and other trypanosomatids exhibit remarkable plasticity, shaped by several distinctive genetic features. Although these features can hinder the [...] Read more.
Parasites of the Leishmania genus are globally distributed and cause various clinical presentations in animals and humans, collectively known as leishmaniasis. The genomes of Leishmania and other trypanosomatids exhibit remarkable plasticity, shaped by several distinctive genetic features. Although these features can hinder the application of next-generation DNA sequencing (NGS) technologies, NGS data have been successfully used to characterize the whole-genome diversity of circulating Leishmania strains. The results complement and are broadly aligned with previous findings obtained with more traditional methods, offering greater resolution when working with geographically closer strains. In this review, we summarize advances over the past two decades in characterizing the genome diversity of Leishmania parasites using NGS strategies. We also discuss the application of these strategies to elucidate other aspects relevant to the epidemiology of these parasites, including their population structure and mode of reproduction. The vast majority of the studies to date have focused on species within the L. donovani/infantum complex or the L. (Viannia) subgenus, highlighting the need to incorporate other relevant underrepresented species and regions from both the Old and New World. Full article
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17 pages, 9111 KB  
Article
A New Deepfake Detection Method with No-Reference Image Quality Assessment to Resist Image Degradation
by Jiajun Jiang, Wen-Chao Yang, Chung-Hao Chen and Timothy Young
Eng 2025, 6(10), 274; https://doi.org/10.3390/eng6100274 (registering DOI) - 11 Oct 2025
Abstract
Deepfake technology, which utilizes advanced AI models such as Generative Adversarial Networks (GANs), has led to the proliferation of highly convincing manipulated media, posing significant challenges for detection. Existing detection methods often struggle with the low-quality or compressed press, which is prevalent on [...] Read more.
Deepfake technology, which utilizes advanced AI models such as Generative Adversarial Networks (GANs), has led to the proliferation of highly convincing manipulated media, posing significant challenges for detection. Existing detection methods often struggle with the low-quality or compressed press, which is prevalent on social media platforms. This paper proposes a novel Deepfake detection framework that leverages No-Reference Image Quality Assessment (NRIQA) techniques, specifically, BRISQUE, NIQE, and PIQUE, to extract quality-related features from facial images. These features are then classified using a Support Vector Machine (SVM) with various kernel functions. We evaluate our method under both intra-dataset and cross-dataset settings. For intra-dataset evaluation, we conduct K-fold cross-validation on two benchmark datasets, DFDC and Celeb-DF (v2), including downsampled versions to simulate real-world degradation. The results show that our method maintains high accuracy even under significant quality loss, achieving up to 98% accuracy on the Celeb-DF (v2) dataset and outperforming several state-of-the-art methods. To improve the transferability of the detection models, we introduce an integrated filtering strategy based on NR-IQA thresholding, which enhances performance in cross-dataset transfer scenarios. This approach yields up to 7% improvement in detection accuracy under challenging cross-domain conditions. Full article
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35 pages, 1382 KB  
Review
Advancements in Drainage Consolidation Technology for Marine Soft Soil Improvement: A Review
by Zhongxuan Chen, Junwei Shu, Sheng Song, Luxiang Wu, Youjun Ji, Chaoqun Zhai, Jun Wang and Xianghua Lai
J. Mar. Sci. Eng. 2025, 13(10), 1951; https://doi.org/10.3390/jmse13101951 (registering DOI) - 11 Oct 2025
Abstract
Marine soft soils are characterized by high compressibility, low strength, and low permeability, which often result in excessive settlement and stability problems. Drainage consolidation methods are widely regarded as effective solutions for improving such soils. This review summarizes recent progress from four perspectives: [...] Read more.
Marine soft soils are characterized by high compressibility, low strength, and low permeability, which often result in excessive settlement and stability problems. Drainage consolidation methods are widely regarded as effective solutions for improving such soils. This review summarizes recent progress from four perspectives: optimization of traditional techniques, combined applications of multiple methods, development of emerging innovative approaches, and advances in drainage element materials and structures. Traditional methods such as surcharge and vacuum preloading have been refined through innovations in loading schemes, drainage improvements, and design approaches, while hybrid combinations with electroosmosis, thermal treatment, and dynamic loading have further enhanced their efficiency and applicability. In parallel, novel techniques such as siphon drainage, aerosol-assisted consolidation, and osmosis-based drainage show promise for sustainable applications. Furthermore, biodegradable and multifunctional drainage elements provide new directions for environmentally friendly and efficient soft soil improvement. Looking ahead, drainage consolidation technology is expected to move toward greener, low-carbon, and intelligent solutions. This review offers a comprehensive reference for engineering practice and a useful basis for guiding future research in marine soft soil improvement. Full article
(This article belongs to the Special Issue Advances in Marine Geotechnical Engineering—2nd Edition)
6 pages, 163 KB  
Editorial
Editorial for Special Issue “Remote Sensing of Precipitation Extremes”
by Ehsan Sharifi, Silas Michaelides and Vincenzo Levizzani
Remote Sens. 2025, 17(20), 3406; https://doi.org/10.3390/rs17203406 (registering DOI) - 11 Oct 2025
Abstract
Recent years have seen tremendous advancements in the field of extreme precipitation monitoring, particularly through the application of remote sensing technologies [...] Full article
(This article belongs to the Special Issue Remote Sensing of Precipitation Extremes)
58 pages, 1997 KB  
Review
Immunomodulatory Activities of Emerging Rare Ginsenosides F1, Rg5, Rk1, Rh1, and Rg2: From Molecular Mechanisms to Therapeutic Applications
by Chang-Eui Hong and Su-Yun Lyu
Pharmaceuticals 2025, 18(10), 1529; https://doi.org/10.3390/ph18101529 (registering DOI) - 11 Oct 2025
Abstract
Ginsenosides, the primary bioactive components of Panax ginseng, have demonstrated significant immunomodulatory potential. While major ginsenosides have been extensively studied, rare ginsenosides produced through deglycosylation, heating, and steaming show enhanced biological activities with improved bioavailability. This review aimed to comprehensively analyze the [...] Read more.
Ginsenosides, the primary bioactive components of Panax ginseng, have demonstrated significant immunomodulatory potential. While major ginsenosides have been extensively studied, rare ginsenosides produced through deglycosylation, heating, and steaming show enhanced biological activities with improved bioavailability. This review aimed to comprehensively analyze the immunomodulatory mechanisms, structure-activity relationships (SARs), therapeutic applications, and clinical translation strategies of five emerging rare ginsenosides: F1, Rg5, Rk1, Rh1, and Rg2. We conducted a comprehensive literature review examining the production methods, immunological effects, molecular mechanisms, pharmacokinetics, safety profiles, and clinical applications of these five compounds. Analysis focused on chemical structures, immune cell modulation, signaling pathways, disease model efficacy, and bioavailability enhancement strategies. Ginsenoside F1 uniquely demonstrated immunostimulatory effects, enhancing natural killer (NK) cell cytotoxicity and macrophage phagocytosis through mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) activation. Conversely, Rg5, Rk1, Rh1, and Rg2 exhibited anti-inflammatory properties via distinct mechanisms: Rg5 through Toll-like receptor 4 (TLR4)/NF-κB inhibition, Rk1 via triple pathway modulation (NF-κB, p38 MAPK, signal transducer and activator of transcription (STAT)), Rh1 by selective p38 MAPK and STAT1 inhibition, and Rg2 through modulation of both central nervous system (neuroinflammation) and peripheral organ systems. Structure-activity analysis revealed that sugar moiety positions critically determine immunological outcomes. Crucially, advanced delivery systems including nanostructured lipid carriers, self-microemulsifying systems, and specialized liposomes have overcome the major translational barrier of poor bioavailability, achieving up to 2.6-fold improvements and enabling clinical development. Safety assessments demonstrated favorable tolerability profiles across preclinical and clinical studies. These five rare ginsenosides represent promising immunomodulatory agents with distinct therapeutic applications. F1’s unique immunostimulatory properties position it for cancer immunotherapy, while the complementary anti-inflammatory mechanisms of Rg5, Rk1, Rh1, and Rg2 offer opportunities for precision medicine in inflammatory diseases. Advanced formulation technologies and optimized production methods now enable their significant clinical translation potential, providing promising therapeutic options for immune-related disorders pending further development. Full article
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