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34 pages, 2126 KB  
Review
A Critical Review of Mycotoxin Contamination in Food and Feed in the Democratic Republic of the Congo and Neighboring Countries: Challenges and Future Directions
by Michel Kawayidiko Kasongo, Arthur Mpanzu Duki, Christophe Tsobo Masiala, Sarah De Saeger and José Diana Di Mavungu
Toxins 2026, 18(4), 182; https://doi.org/10.3390/toxins18040182 - 10 Apr 2026
Abstract
Mycotoxin contamination remains a persistent threat to food safety in the Democratic Republic of the Congo (DRC) and neighboring countries, driven by conducive tropical agroecological conditions, inadequate post-harvest practices, and limited regulatory governance. This critical narrative review (2009–2024) synthesizes the occurrence data for [...] Read more.
Mycotoxin contamination remains a persistent threat to food safety in the Democratic Republic of the Congo (DRC) and neighboring countries, driven by conducive tropical agroecological conditions, inadequate post-harvest practices, and limited regulatory governance. This critical narrative review (2009–2024) synthesizes the occurrence data for major staple foods (maize, peanuts, cassava, sorghum, millet, and beans) and dairy products compiled from Google Scholar, ScienceDirect, MDPI and institutional sources. It examines the co-occurrence patterns, exposure pathways, and analytical and regulatory gaps. Warm, humid lowland environments favor Aspergillus and aflatoxins, whereas cooler, humid highland zones promote Fusarium, fumonisins, and deoxynivalenol. Across commodities, contamination intensifies along food value chains through inadequate drying, non-hermetic storage, insect damage, and prolonged handling, with processed products generally exhibiting the highest levels of mycotoxins. Regulated mycotoxins, including aflatoxins, fumonisins, trichothecenes, ochratoxins, and zearalenone, frequently exceed European Union (EU), East African Community (EAC), and Codex Alimentarius Commission (CAC) limits in staple foods. Their co-occurrence is widespread, including emerging mycotoxins such as beauvericin and enniatins, particularly in maize- and peanut-based products, raising concerns about potential additive or synergistic effects. Aflatoxin M1 in milk highlights plant–feed–animal–human transfer within a One Health framework. Despite increasing evidence, the available data remain fragmented and heterogeneous; rapid tests dominate, while few studies employ multi-mycotoxin LC-MS/MS methods. Cross-border trade between countries, such as Uganda, Tanzania, Zambia and Angola, facilitates the circulation of contaminated commodities in the absence of harmonized standards and risk-based controls. Priorities include harmonized regional surveillance, biomarker-based co-exposure assessment, cost-effectiveness evaluation of mitigation strategies, and regulatory alignment at borders. Coordinated, multisectoral action is essential to reduce chronic dietary exposure and improve food safety across the region. Full article
27 pages, 1243 KB  
Review
The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease
by Anna Kotlyarova, Aleksandra Iskrina and Stanislav Kotlyarov
Int. J. Mol. Sci. 2026, 27(8), 3399; https://doi.org/10.3390/ijms27083399 - 10 Apr 2026
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in the world. The disease progresses from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The modern concept of [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in the world. The disease progresses from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The modern concept of “multiple parallel hits” interprets disease progression as the result of the synergistic action of lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, proinflammatory signals, and gut–liver axis dysfunction. Against the background of the limited translation of preclinical data from animal models due to interspecies differences, the importance of human-oriented in vitro platforms compatible with controlled design and high-throughput screening is increasing. The current review analyzes MASLD models based on the HepG2 cell line, systematizing steatosis induction protocols, evaluating the metabolic characteristics and limitations of this cell, and comparing 2D monocultures, 3D systems, and co-cultures. HepG2 has been shown to demonstrate a predictable steatogenic response to free fatty acids (FFAs) and is convenient for reproducing early stages of pathogenesis and primary pharmacological selection of compounds. At the same time, key limitations of the model are highlighted, namely tumor origin, glycolytic shift (Warburg effect), reduced β-oxidation, impaired very-low-density lipoprotein (VLDL) assembly and secretion, and sharply reduced cytochrome P450 (CYP450) activity, as well as limited reproducibility of fructose-induced de novo lipogenesis (DNL). Comparative analysis demonstrates an increase in physiological relevance with the transition from 2D to 3D and multicomponent co-cultures, accompanied by increased complexity and cost, but allowing for the modeling of inflammation and fibrogenesis. The review justifies approaches to selecting the appropriate platform based on the specific research task. Full article
(This article belongs to the Special Issue Molecular Insights into Chronic Liver Disease and Liver Failure)
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21 pages, 5147 KB  
Article
Self-Humidifying and Super-Protonic Conductivity of SPEEK-Based Composite Proton Exchange Membranes Incorporated by Functionalized MXene and Modified TiO2 Nanofillers
by Manting Huang, Ai Song, Xingliu Ben, Weijia Ji, Yuxuan Pan and Huaxin Rao
Nanomaterials 2026, 16(8), 446; https://doi.org/10.3390/nano16080446 - 8 Apr 2026
Viewed by 150
Abstract
MXene, as a suitable and alternative 2D nanofiller incorporated into a proton exchange membrane (PEM), has recently received considerable attention because of desired mechanical stability, promising conductivity, and active surface functional groups. However, agglomeration or sedimentation in PEMs, as well as the water [...] Read more.
MXene, as a suitable and alternative 2D nanofiller incorporated into a proton exchange membrane (PEM), has recently received considerable attention because of desired mechanical stability, promising conductivity, and active surface functional groups. However, agglomeration or sedimentation in PEMs, as well as the water retention capacity under low humidity of MXene, are limiting factors in the field of PEMs. In this paper, modified MXene and TiO2 nanoparticles used as functional nanofillers were incorporated into sulfonated poly (ether ether ketone) (SPEEK) to prepare novel SPEEK-based composite PEMs. The effects of the nanofiller contents on self-humidifying and protonic conductivity of the composite PEMs were also investigated under different temperatures. When the contents of functionalized MXene and modified TiO2 are 5 wt.%, proton conductivity, water uptake and methanol permeability of the composite PEMs can be up to 0.143 S/cm, 60% and 2.27 × 10−7 cm2/s, respectively, which represent increases of about 192%, about 38% and a decrease of 47%, respectively, compared with that of primary SPEEK PEM. Under the synergistic action of functionalized MXene providing a higher number of exchangeable proton sites, modified TiO2 with inherent hydrophilicity enhancing water retention and Pt providing catalytic sites for the H2/O2 reaction to generate water in situ, the self-humidifying capability and proton conductivity of the composite PEMs were improved significantly. Full article
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24 pages, 3563 KB  
Systematic Review
A Systematic Review on Plant-Atmosphere Synergy: Dual Purification Strategies for PM2.5 and O3 Pollution
by Qinling Wang, Shaoning Li, Shuo Chai, Na Zhao, Xiaotian Xu, Yutong Bai, Bin Li and Shaowei Lu
Sustainability 2026, 18(8), 3657; https://doi.org/10.3390/su18083657 - 8 Apr 2026
Viewed by 89
Abstract
Globally, the combined pollution of fine particulate matter (PM2.5) and ground-level ozone (O3) poses severe challenges to public health and sustainable urban development. Recent data indicate that the annual average PM2.5 concentration in the vast majority of cities [...] Read more.
Globally, the combined pollution of fine particulate matter (PM2.5) and ground-level ozone (O3) poses severe challenges to public health and sustainable urban development. Recent data indicate that the annual average PM2.5 concentration in the vast majority of cities worldwide fails to meet World Health Organization safety standards, with air pollution causing millions of premature deaths annually. As a nature-based solution, the purification efficacy of vegetation remains poorly quantified due to unclear coupling mechanisms with local meteorological conditions. This study systematically reviewed and synthesized 229 empirical studies published between 2000 and 2025 from Web of Science and China National Knowledge Infrastructure (CNKI), aiming to clarify the quantitative relationships and regulatory mechanisms of plant–meteorological synergistic purification of PM2.5–O3. Following double-blind independent screening (κ = 0.85) and data extraction, a quantitative minimal feasible synthesis approach was adopted due to high data heterogeneity. The results indicated the following. (1) The median canopy purification efficiency of urban vegetation for PM2.5 was 18.2% (IQR: 12.5–30.1%, n = 17), with a median dry deposition velocity (Vd–PM) of 0.05 cm s−1 (0.02–30 cm s−1, n = 15). The median dry deposition velocity (Vd–O3) for O3 was 0.55 cm s−1 (0.12–1.82 cm s−1, n = 8), with non-stomatal deposition contributing approximately 35%. (2) Meteorological factors exhibit nonlinear regulation: relative humidity (RH) > 70% significantly enhances PM2.5 adsorption, wind speeds of 1.5–3.0 m s−1 are optimal for PM2.5 deposition, and temperatures > 30 °C generally inhibit plant uptake of both pollutants (n = 7). (3) Functional traits strongly correlate with purification efficacy: species with high leaf roughness (R2 = 0.8), high stomatal conductance, and low BVOC emissions (e.g., Ginkgo biloba, Platycladus orientalis) exhibit optimal synergistic purification potential. Species with high BVOC emissions (Populus przewalskii, Eucalyptus robusta) can increase daily net O3 pollution equivalents by up to 86 g and must be strictly avoided. Based on quantitative evidence, a green space planning decision matrix indexed by climate zone and pollution type was developed, specifying vegetation configuration patterns, functional group selection, and key design parameters (canopy closure, green belt width, etc.) for different scenarios. This study provides an actionable scientific basis for precision planning and climate-adaptive management of urban green infrastructure. Full article
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20 pages, 1005 KB  
Article
Evaluating the Sustainability of Urban Energy Systems: A Policy-Economic-Environmental Analysis of the APPA in China’s ‘2+26’ Cities
by Bingqi Zhang, Luyuan Tang and Haotian Zhang
Energies 2026, 19(7), 1802; https://doi.org/10.3390/en19071802 - 7 Apr 2026
Viewed by 147
Abstract
In the context of global energy system transformation and the pursuit of regional sustainability, China’s Air Pollution Control and Prevention Action Plan (APPA) targets both pollution reduction and carbon mitigation, serving as a critical policy instrument for coordinating the energy-economy-environment nexus in the [...] Read more.
In the context of global energy system transformation and the pursuit of regional sustainability, China’s Air Pollution Control and Prevention Action Plan (APPA) targets both pollution reduction and carbon mitigation, serving as a critical policy instrument for coordinating the energy-economy-environment nexus in the “2+26” cities. This study employs a quasi-natural experiment with a difference-in-difference (DID) method to assess the synergistic impact of this energy-related policy on these cities. Results show that APPA significantly reduces PM2.5 and carbon emissions by 5.56% and 9.89%, respectively, demonstrating a successful alignment of short-term environmental targets with long-term decarbonization goals. Heterogeneity analysis reveals that large cities with higher institutional capacity are more effective in reducing both pollutants, while resource-based cities achieve more PM2.5 reduction, and non-resource-based cities excel in low-carbon energy transition. Mechanism analysis indicates that APPA promotes these outcomes by optimizing the energy-intensive industrial structure and fostering green technological innovation. This study highlights the effectiveness of integrated governance frameworks in enhancing air quality and reducing carbon emissions, providing crucial insights for redesigning sustainable energy policies and managing the socio-economic disruptions of just transitions in rapidly developing regions. Full article
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21 pages, 4286 KB  
Article
Metabolite-Mediated Antioxidant-Rich Bacterial Isolates for the Control of Anthracnose Disease and Enhancement of the Post-Harvest Shelf Life of Mango (Mangifera indica L.)
by T. Damodaran, Karma Beer, Prasenjit Debnath, Sumit K. Soni, Maneesh Mishra, M. Muthukumar, Nisha Sulakhe and Prabhat Kumar Shukla
Plants 2026, 15(7), 1130; https://doi.org/10.3390/plants15071130 - 7 Apr 2026
Viewed by 235
Abstract
Mango (Mangifera indica L.), being a climacteric fruit, is highly perishable due to rapid ripening and post-harvest diseases like anthracnose, which significantly shorten its shelf life and limit long-distance sea export. To mitigate these constraints, a chemical-free secondary metabolite-based formulation (SMsF) was [...] Read more.
Mango (Mangifera indica L.), being a climacteric fruit, is highly perishable due to rapid ripening and post-harvest diseases like anthracnose, which significantly shorten its shelf life and limit long-distance sea export. To mitigate these constraints, a chemical-free secondary metabolite-based formulation (SMsF) was developed to delay ripening and control post-harvest anthracnose during storage. The SMsF possesses dual-action properties and is derived from the culture filtrate of Priestia aryabhattai, exhibiting ACC deaminase activity that restricts ethylene formation. It is also rich in antifungal compounds such as vanillic acid, hydroxybenzoic acid, cryptochlorogenic acid, palmitic acid, and BBIT, which inhibit anthracnose development. Additionally, it contains antioxidants including quercetin, coumaryl quinic acid, oleic acid, and acetylglycitin that enhance shelf life and disease resistance. The efficacy of SMsF was evaluated in mango cv. Banganapalli was stored at 12 ± 1 °C and 85–90% relative humidity under simulated reefer conditions (SRC). Integration of gamma irradiation with SMsF provided superior results in disease control and shelf-life extension. The combined treatment maintained higher fruit firmness (0.86 kg cm−2), optimal total soluble solids (14.3 °B), desirable acidity (0.22%), and complete suppression of anthracnose (PDI = 0) up to 40 days of storage under SRC compared with the control. The findings conclusively demonstrate that the synergistic application of SMsF and gamma irradiation effectively regulates ripening, enhances fruit quality, and ensures complete disease suppression, thereby significantly extending storage life. This approach holds strong scientific and commercial significance as a sustainable, residue-free, and export-oriented technology capable of improving long-distance transportation, reducing post-harvest losses, and promoting safe mango trade. Full article
(This article belongs to the Section Plant Protection and Biotic Interactions)
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10 pages, 2864 KB  
Article
Fabrication of Superhydrophobic Micro–Nanostructures on Pristine SLM-Ti Surfaces
by Xuetong Sun, Hao Sun, Xiue Ren and Changren Zhou
Micromachines 2026, 17(4), 454; https://doi.org/10.3390/mi17040454 - 7 Apr 2026
Viewed by 165
Abstract
Superhydrophobic surfaces are typically achieved through the synergistic integration of appropriate nanostructures and low-surface-energy chemical compositions. This study presents a novel and facile method for constructing a superhydrophobic hierarchical structure directly on a pristine selective laser melting (SLM) titanium surface. The intrinsic partially [...] Read more.
Superhydrophobic surfaces are typically achieved through the synergistic integration of appropriate nanostructures and low-surface-energy chemical compositions. This study presents a novel and facile method for constructing a superhydrophobic hierarchical structure directly on a pristine selective laser melting (SLM) titanium surface. The intrinsic partially melted Ti particles, which are inherent to the SLM fabrication process, were strategically utilized as a natural microscale template for the in situ growth of TiO2 nanotubes via electrochemical anodization. Three distinct micro/nano-topographies were successfully fabricated, integrating the spherical microparticles with either conventional TiO2 nanotube arrays or separated nanotube arrays. The results demonstrate that the resulting superhydrophobic behavior can be effectively regulated by two key factors: the liquid–solid contact mode at the microscale and the strength of capillary action within the nanostructures. Notably, these characteristics can be tailored by controlling the nanotube diameter and intertubular spacing. These findings contribute to a deeper understanding of the role of micro–nano hierarchical structures in engineering superhydrophobic surfaces, thereby opening new avenues for advanced applications. Full article
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32 pages, 1364 KB  
Article
XRL-LLM: Explainable Reinforcement Learning Framework for Voltage Control
by Shrenik Jadhav, Birva Sevak and Van-Hai Bui
Energies 2026, 19(7), 1789; https://doi.org/10.3390/en19071789 - 6 Apr 2026
Viewed by 296
Abstract
Reinforcement learning (RL) agents are increasingly deployed for voltage control in power distribution networks. However, their opaque decision-making creates a significant trust barrier, limiting their adoption in safety-sensitive operational settings. This paper presents XRL-LLM, a novel framework that generates natural language explanations for [...] Read more.
Reinforcement learning (RL) agents are increasingly deployed for voltage control in power distribution networks. However, their opaque decision-making creates a significant trust barrier, limiting their adoption in safety-sensitive operational settings. This paper presents XRL-LLM, a novel framework that generates natural language explanations for RL control decisions by combining game-theoretic feature attribution (KernelSHAP) with large language model (LLM) reasoning grounded in power systems domain knowledge. We deployed a Proximal Policy Optimization (PPO) agent on an IEEE 33-bus network to coordinate capacitor banks and on-load tap changers, successfully reducing voltage violations by 90.5% across diverse loading conditions. To make these decisions interpretable, KernelSHAP identifies the most influential state features. These features are then processed by a domain-context-engineered LLM prompt that explicitly encodes network topology, device specifications, and ANSI C84.1 voltage limits.Evaluated via G-Eval across 30 scenarios, XRL-LLM achieves an explanation quality score of 4.13/5. This represents a 33.7% improvement over template-based generation and a 67.9% improvement over raw SHAP outputs, delivering statistically significant gains in accuracy, actionability, and completeness (p<0.001, Cohen’s d values up to 4.07). Additionally, a physics-grounded counterfactual verification procedure, which perturbs the underlying power flow model, confirms a causal faithfulness of 0.81 under critical loading. Finally, five ablation studies yield three broader insights. First, structured domain context engineering produces synergistic quality gains that exceed any single knowledge component, demonstrating that prompt composition matters more than the choice of foundational model. Second, even an open source 8B-parameter model outperforms templates given the same prompt, confirming the framework’s backbone-agnostic value. Most importantly, counterfactual faithfulness increases alongside load severity, indicating that post hoc attributions are most reliable in the high-stakes regimes where trustworthy explanations matter most. Full article
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36 pages, 2452 KB  
Review
Plant-Derived Bioactive Compounds: Antioxidation, Autophagy, and Translational Applications in Skin Protection
by Liangyu Zhu, Mengsha Li, Dianwen Wei and Liping Zhou
Curr. Issues Mol. Biol. 2026, 48(4), 377; https://doi.org/10.3390/cimb48040377 - 5 Apr 2026
Viewed by 197
Abstract
Oxidative stress from exogenous insults is a major driver of skin aging and hyperpigmentation. Plant-derived bioactive compounds represent promising multifunctional agents with protective effects on skin. They meet the demand for natural, safe skin-protective agents with well-defined action mechanisms. However, current studies lack [...] Read more.
Oxidative stress from exogenous insults is a major driver of skin aging and hyperpigmentation. Plant-derived bioactive compounds represent promising multifunctional agents with protective effects on skin. They meet the demand for natural, safe skin-protective agents with well-defined action mechanisms. However, current studies lack an integrated understanding of their dual cellular protective mechanisms: antioxidation and autophagy. A unified “component–pathway–efficacy” regulatory network remains lacking, which limits mechanistic insights into skin protection. To address this gap, this comprehensive narrative review retrieved literature from four authoritative databases: PubMed, Web of Science, Scopus, and Wiley Online Library. With targeted keyword retrieval, 129 core studies published between 2021 and 2025 were selected for synthesis. The selection was based on relevance, methodological rigor, and scientific impact. This review constructs a novel “antioxidation–autophagy” synergistic regulatory model. It also establishes a consolidated dual-mechanism framework outlining the “component–pathway–efficacy” axis. This framework reduces knowledge fragmentation across natural product research, skin biology and translational molecular biology. This work integrates the dual protective mechanisms of plant-derived bioactive compounds for skin protection and translational applications. It provides a theoretical basis for understanding their molecular regulatory logic and facilitates further mechanistic studies and translational research on skin protection. Full article
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23 pages, 2214 KB  
Review
Natural Alkaloids as Antimicrobial Agents: Mechanisms, Potentials and Challenges
by Xi-Zhong Zhang, Ming-Xia Chen, Rui Hou, Wan-Qin Wang, Zhen-Dan He, Jie-Shu You and Xun Song
Molecules 2026, 31(7), 1204; https://doi.org/10.3390/molecules31071204 - 5 Apr 2026
Viewed by 458
Abstract
Antimicrobial resistance (AMR) poses a significant global health threat, with multidrug-resistant pathogens undermining the effectiveness of conventional antibiotics. Natural alkaloids, a diverse group of nitrogen-containing compounds mainly derived from plants, are gaining attention as potential antimicrobial agents due to their broad-spectrum activity, structural [...] Read more.
Antimicrobial resistance (AMR) poses a significant global health threat, with multidrug-resistant pathogens undermining the effectiveness of conventional antibiotics. Natural alkaloids, a diverse group of nitrogen-containing compounds mainly derived from plants, are gaining attention as potential antimicrobial agents due to their broad-spectrum activity, structural variety, and unique mechanisms of action. This review examines the antimicrobial properties of natural alkaloids, classifying them by chemical structure (e.g., quinoline, isoquinoline, pyridine, indole, and imidazole alkaloids). Their antibacterial, antifungal, and antiviral activities are discussed, along with the mechanisms by which they target pathogenic microorganisms, including disruption of cell walls and membranes, inhibition of protein synthesis, interference with DNA replication, and viral assembly. The review also explores the synergistic effects of alkaloids when combined with conventional antimicrobial agents. Alkaloids demonstrate potent antimicrobial activity against various pathogens. Quinoline alkaloids, such as quinine, inhibit DNA replication and damage cell membranes. Isoquinoline alkaloids like berberine and sanguinarine exhibit broad-spectrum antibacterial effects. Pyridine alkaloids, including nicotine, disrupt bacterial membranes. In fungi, alkaloids such as sanguinarine and indole derivatives prevent cell wall synthesis and spore germination. Antiviral alkaloids like lycorine target viral RNA polymerases. Additionally, alkaloids enhance the activity of traditional antibiotics by overcoming resistance. Natural alkaloids represent a promising source of antimicrobial agents with diverse mechanisms to combat AMR. Future research should focus on optimizing alkaloid structures, ensuring safety and efficacy, and exploring combination therapies to address the escalating AMR challenge. Full article
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25 pages, 4302 KB  
Article
Optimizing Carbon Emission Reduction Pathways in Prefabricated Building Materialization Stages: A Cloud Entropy and NK Model Approach
by Daopeng Wang, Hang Liu, Jiaming Xu, Ping Liu and Yu Fang
Appl. Sci. 2026, 16(7), 3539; https://doi.org/10.3390/app16073539 - 4 Apr 2026
Viewed by 167
Abstract
In response to escalating global environmental challenges, mitigating carbon emissions in the construction sector has emerged as a critical strategy for addressing climate change. As reported by the United Nations Environment Programme (UNEP) and the International Energy Agency (IEA), the construction industry remains [...] Read more.
In response to escalating global environmental challenges, mitigating carbon emissions in the construction sector has emerged as a critical strategy for addressing climate change. As reported by the United Nations Environment Programme (UNEP) and the International Energy Agency (IEA), the construction industry remains a major contributor to global greenhouse gas emissions. This study investigates the influencing factors and optimization pathways for embodied carbon emissions during the materialization phase of prefabricated buildings. Through longitudinal field research at a large-scale precast component factory in western China, key carbon emission factors were identified using Min–Max normalization and Principal-Components Analysis (PCA). A cloud entropy–based evaluation model was further developed to quantify the emission weights of 32 factors. The results reveal the existence of ‘leveraging effects’ among emission factors, wherein certain low-weight factors exert disproportionate influence on systemic carbon reduction because of their cascading impacts on other variables. Prioritizing factors with greater leveraging potential is imperative for the formulation of effective emission reduction policies. This study leverages NK model simulations (10,000 iterations), to predict the reduction potential of each factor and identifies four indicators with the most significant leveraging effects. Strategic recommendations are proposed that emphasize a synergistic approach that integrates direct emission control and indirect cascading optimization. These findings provide actionable insights for achieving systemic carbon reduction in prefabricated building systems. Full article
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21 pages, 8505 KB  
Article
Biophysicochemical Design of a Dual-Function Hydrogel for Synergistic Shock-Absorption and Anti-Inflammatory Action for TMD Therapy
by Diego Garcia Miranda, Lucas de Paula Ramos, Pyetra Claro de Camargo, Nicole Fernanda dos Santos Lopes, Thalita Sani-Taiariol, Mauricio Ribeiro Baldan, Cristina Pacheco-Soares, Bruno Henrique Godoi, Kerstin Gritsch, Brigitte Grosgogeat and Alexandre Luiz Souto Borges
Polysaccharides 2026, 7(2), 40; https://doi.org/10.3390/polysaccharides7020040 - 2 Apr 2026
Viewed by 211
Abstract
Temporomandibular disorder (TMD) is recognized as a major public health problem, causing pain and physiological and psychosocial limitations. In this context, the present in vitro study investigated the synthesis of a hyaluronic acid (HA) hydrogel with hydrocortisone (Hyd), designed to enhance joint lubrication [...] Read more.
Temporomandibular disorder (TMD) is recognized as a major public health problem, causing pain and physiological and psychosocial limitations. In this context, the present in vitro study investigated the synthesis of a hyaluronic acid (HA) hydrogel with hydrocortisone (Hyd), designed to enhance joint lubrication by reducing mechanical friction and delivering the anti-inflammatory drug. The hydrogels were prepared with 3% HA (30 mg/mL) and Hyd—0.125% (1.25 mg/mL), 0.250% (2.5 mg/mL), 0.500% (5 mg/mL), or 1% (10 mg/mL). Physicochemical analyses included Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TGA), rheological tests (frequency, amplitude, and temperature ramp scans), and field emission scanning electron microscopy (FESEM), performed before and after sterilization and cycling. In addition, cytocompatibility was evaluated by protocol OECD 129 and confocal microscopy, as well as genotoxicity (OECD487) in mouse macrophages (RAW 264.7 strain) per 24 h of exposure. FTIR demonstrated the spectral signatures of the compounds with no covalent interactions between the drugs, as well thermal stability on TGA. Rheology demonstrated that Hyd protected the HA structure after autoclaving, maintaining viscoelastic properties. SEM confirmed homogeneous porous morphology. Biological assays showed cell viability > 70%, but with a dose-dependent increase in genotoxicity (4–17 micronuclei). Confocal analysis revealed increasing cytotoxicity at high Hyd concentrations, indicating a balance between biocompatibility and adverse effects at concentrations ≤ 0.5%. Among the tested formulations, the 3% HA + 0.250% Hyd hydrogel provided the best balance of viscoelastic stability, cytocompatibility, and low genotoxicity, supporting its potential as a dual-function intra-articular candidate for TMD therapy. Full article
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21 pages, 1084 KB  
Review
Review of Structural Modification and Development of Novel Tramadol Derivatives
by Ni Wang, Xiaoli Zhou, Jingwen Wang, Lixin Sun, Bo Liu and Lihui Yin
Molecules 2026, 31(7), 1177; https://doi.org/10.3390/molecules31071177 - 2 Apr 2026
Viewed by 483
Abstract
Tramadol acts via μ-opioid receptor agonism and monoamine reuptake inhibition but is clinically limited by metabolic dependence, interindividual variability, and addiction risks. Structural modification aims to resolve these limitations. This review systematically summarizes tramadol’s structure–activity relationships and mechanisms, focusing on key strategies for [...] Read more.
Tramadol acts via μ-opioid receptor agonism and monoamine reuptake inhibition but is clinically limited by metabolic dependence, interindividual variability, and addiction risks. Structural modification aims to resolve these limitations. This review systematically summarizes tramadol’s structure–activity relationships and mechanisms, focusing on key strategies for structural optimization. Major advances include: (i) synergistic strategies, such as tramadol–celecoxib cocrystals (tramadol and celecoxib coexist in the supramolecular crystal network at a 1:1 molar ratio), achieving multimodal analgesia at lower doses; (ii) mechanism-balancing strategies such as tapentadol (derivatives of tramadol with a dual mechanism of action), which enhance μ-opioid agonism and norepinephrine reuptake inhibition while attenuating serotonergic effects to improve efficacy; (iii) metabolic optimization utilizing M1 analogues to circumvent CYP2D6 polymorphisms (tramadol is metabolized by this enzyme into the active metabolite M1 to exert analgesic effects); and (iv) pharmacophore optimization leveraging tramadol–morphine homology and “message–address” concepts to design selective ligands. Novel derivatives demonstrate improved potency and metabolic stability but continue to face challenges regarding opioid risks and clinical translation. Future research should integrate rational drug design, delivery systems, and personalized medicine to facilitate the development of safer next-generation analgesics. Full article
(This article belongs to the Special Issue Small-Molecule Targeted Drugs)
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21 pages, 6834 KB  
Article
Plasma-Activated Hydrogen Peroxide for Advanced Oxidation of Hydraulic Fracturing Flowback Fluid
by Meiqi Shi, Fuping Feng, Jianwei Zhang, Hong Jiang, Xueqin Wang and Xu Han
Appl. Sci. 2026, 16(7), 3438; https://doi.org/10.3390/app16073438 - 1 Apr 2026
Viewed by 278
Abstract
Fracturing flowback fluid is a complex wastewater generated during oil extraction, characterized by high concentrations of organic matter, suspended solids, salts, and various chemical additives, posing substantial risks to both surface water and groundwater if discharged directly. This study investigated the treatment of [...] Read more.
Fracturing flowback fluid is a complex wastewater generated during oil extraction, characterized by high concentrations of organic matter, suspended solids, salts, and various chemical additives, posing substantial risks to both surface water and groundwater if discharged directly. This study investigated the treatment of simulated fracturing flowback fluid prepared with guar gum using low-temperature plasma coupled with hydrogen peroxide technology. The degradation efficacy and preliminary mechanism of the combined system on organic pollutants were explored. Through a systematic optimization of operational parameters in the laboratory, the optimal treatment conditions were determined as a discharge voltage of 18 kV, a hydrogen peroxide addition of 5%, an initial pH of 11, and a treatment time of 110 min. Under these conditions, the synergistic system achieved 89.59 percent degradation of organic pollutants and 92.96 percent chemical oxygen demand removal. The results revealed that the combined action induced breakage of guar gum polymer chains, thereby enhancing degradation efficiency while effectively controlling fluid viscosity. This technology establishes a practical treatment approach for simulated fracturing flowback fluids containing guar gum, thereby facilitating better waste management in the energy sector. Full article
(This article belongs to the Section Environmental Sciences)
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21 pages, 25312 KB  
Article
Structure Activity Relationships of Multitarget Coumarins on Inhibitory Aggregation of Platelets: An Integrated In Vitro and In Silico Study
by Ixchel Ramírez-Camacho, Fernando León Cedeño, José Germán Vázquez Cuevas, Eva Florencia Lejarazo Gómez, Ulises Martínez-Ortega, Mirthala Flores-García, Ana María Mejía-Domínguez, Aurora de la Peña-Díaz and Fausto Alejandro Jiménez-Orozco
Biophysica 2026, 6(2), 26; https://doi.org/10.3390/biophysica6020026 - 31 Mar 2026
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Abstract
Novel pharmacological approaches advocate developing multitarget drugs, that is, molecules capable of simultaneously acting on two or more pharmacological targets to produce synergistic effects from a single compound in each disease. This strategy may help reduce required doses and prevent drug–drug interactions typically [...] Read more.
Novel pharmacological approaches advocate developing multitarget drugs, that is, molecules capable of simultaneously acting on two or more pharmacological targets to produce synergistic effects from a single compound in each disease. This strategy may help reduce required doses and prevent drug–drug interactions typically associated with polypharmacy. Coumarins are natural products with diverse pharmacological activities, including antioxidant, anti-inflammatory, anticancer, neuroprotective, cardioprotective, and antithrombotic effects. The pleiotropic actions of these molecules suggest that modifying the coumarin structure could yield new multi-target antiplatelet agents with greater efficacy and safety than those currently available in clinical practice. In this work, we began with a theoretical approach using molecular docking and designed three coumarins that simultaneously inhibited platelet aggregation induced by epinephrine, collagen, and ADP. Experimentally, we evaluated the structure activity relationship of three coumarins: (A) 6,7-dimethoxy-3-(1H-pyrrol-1-yl)-2H-chromen-2-one, (B) 7,8-dimethoxy-3-(1H-pyrrol-1-yl)-2H-chromen-2-one, and (C) 3-(1H-imidazol-1-yl)-6,7-dimethoxy-2H-chromen-2-one. In silico studies suggest that compounds B and C may exhibit antagonistic interactions at the α2-adrenergic, GPVI collagen, and P2Y12 ADP receptors. Additionally, molecular docking indicates essential interactions between the compounds and the GPIIb/IIIa fibrinogen receptor. Full article
(This article belongs to the Special Issue Biophysical Insights into Small Molecule Inhibitors)
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