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22 pages, 417 KB  
Article
Codings of B-Integers in Cantor Numeration Systems as Generators of Aperiodic Potentials
by Lubomíra Dvořáková, Zuzana Masáková and Edita Pelantová
Symmetry 2026, 18(3), 538; https://doi.org/10.3390/sym18030538 (registering DOI) - 21 Mar 2026
Abstract
Cantor real numeration systems provide a natural algebraic source of self-similar aperiodic structures, extending the classical β-integers framework introduced in quasicrystal modeling by Gazeau. We study how the choice of algebraic parameters of the base [...] Read more.
Cantor real numeration systems provide a natural algebraic source of self-similar aperiodic structures, extending the classical β-integers framework introduced in quasicrystal modeling by Gazeau. We study how the choice of algebraic parameters of the base B=(βi)iZ influences the self-similarity and other combinatorial properties of the encoding symbolic sequence. These properties, namely repetitivity and palindromicity, are key features deciding the character of the spectrum of the underlying one-dimensional Schrödinger operator with aperiodic potential. Full article
28 pages, 6442 KB  
Article
Chemical Profiling and Photoprotective Activity of Extracts from Colombian Passiflora Byproducts
by María Cabeza, Cindy Lucero López, Geison Modesti Costa, Mónica Ávila-Murillo, Freddy A. Ramos, Yolima Baena, Marcela Aragón Novoa and Leonardo Castellanos
Plants 2026, 15(6), 972; https://doi.org/10.3390/plants15060972 (registering DOI) - 21 Mar 2026
Abstract
Agro-industrial byproducts from Colombian Passiflora species represent an underexplored source of chemically diverse metabolites with promising cosmetic and pharmaceutical potential. This study investigated the chemical profiles and photoprotective potential of polar extracts obtained from byproducts (leaves, pericarps, and seeds) of six commercially relevant [...] Read more.
Agro-industrial byproducts from Colombian Passiflora species represent an underexplored source of chemically diverse metabolites with promising cosmetic and pharmaceutical potential. This study investigated the chemical profiles and photoprotective potential of polar extracts obtained from byproducts (leaves, pericarps, and seeds) of six commercially relevant Passiflora species cultivated in Colombia (P. ligularis, P. edulis var. edulis, P. edulis var. flavicarpa, P. maliformis, P. quadrangularis and P. tarminiana × P. tripartita). Butanolic fractions from leaves and pericarps and hydroethanolic seed extracts were analyzed using 1H NMR, GC-FID, GC-MS and UHPLC-qTOF. NMR profiling revealed aromatic signals mainly associated with flavonoids and stilbenoids in leaves and pericarps, while seeds exhibited abundant fatty acids, particularly linoleic acid. Molecular networking enabled the visualization of chemical diversity and supported the identification of 74 metabolites, including flavonoids, saponins, and stilbenoids, using Global Natural Products Social Molecular Networking (GNPS), SIRIUS (Version 6.0.5) software, and comparison with the literature. In vitro spectrophotometric photoprotective evaluation using the Mansur equation at 200 ppm showed that leaf extracts exhibited the highest sun protection factor (SPF) values, followed by seeds and pericarps, consistent with their phenolic composition. All active extracts demonstrated broad-spectrum protection, with high UVA ratios and critical wavelength values. These findings highlight the potential of Passiflora byproducts as sustainable sources of natural photoprotective agents for cosmetic applications. Full article
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19 pages, 1173 KB  
Article
Molecular Basis of Sperm Methylome Response to Aging and Stress
by Olatunbosun Arowolo, Jiahui Zhu, Karolina Nowak, J. Richard Pilsner and Alexander Suvorov
Biology 2026, 15(6), 504; https://doi.org/10.3390/biology15060504 (registering DOI) - 21 Mar 2026
Abstract
Aging and stress-related factors affect sperm DNA methylation in regions associated with genes responsible for embryonic development. The stochastic epigenetic variation hypothesis holds potential to explain these patterns, proposing that, in response to stressors, naturally variable methylation regions (VMRs) associated with morphogenetic genes [...] Read more.
Aging and stress-related factors affect sperm DNA methylation in regions associated with genes responsible for embryonic development. The stochastic epigenetic variation hypothesis holds potential to explain these patterns, proposing that, in response to stressors, naturally variable methylation regions (VMRs) associated with morphogenetic genes exhibit increased methylation variation to diversify phenotypes and improve the chances of survival of the genetic lineage. Here, we test predictions from this hypothesis using mouse and rat sperm DNA methylation data from publicly available sources. Specifically, we identify VMRs and analyze their overlap with regions differentially methylated (DMRs) in response to aging, stressors, and with various genomic elements. We demonstrate that the nature of the DNA regions, rather than the nature of the stressor, determines the response of the sperm methylome to aging and stress, and propose a model that explains shifts in methylation within VMRs through stochastic changes, whereby initially hypermethylated regions lose methylation and initially hypomethylated regions gain methylation. VMRs are depleted of open chromatin regions and histones in male germ cells and are enriched for a binding motif for ZFP42, an epigenetic remodeler. This knowledge may open opportunities for the development of interventions to control epigenetic information transfer via germ cells. Full article
(This article belongs to the Special Issue Feature Papers on Developmental and Reproductive Biology)
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15 pages, 952 KB  
Review
Citrus Limonene as a Potential Source of Biopesticides Against Maize Weevils
by Yamkela Silwanyana, Ayodeji Oluwabunmi Oriola, Gugulethu Mathews Miya, Yiseyon Sunday Hosu, Adebola Omowunmi Oyedeji, Opeoluwa Oyehan Oyedeji and Simon Kamande Kuria
Agriculture 2026, 16(6), 703; https://doi.org/10.3390/agriculture16060703 - 20 Mar 2026
Abstract
The maize weevil is a major postharvest pest of stored maize, causing substantial quantitative and qualitative grain losses and posing a serious threat to food security. In many regions of the world, particularly in developing countries where maize is a staple crop, maize [...] Read more.
The maize weevil is a major postharvest pest of stored maize, causing substantial quantitative and qualitative grain losses and posing a serious threat to food security. In many regions of the world, particularly in developing countries where maize is a staple crop, maize weevil infestations can account for up to 50% of postharvest maize losses annually. Traditionally, synthetic pesticides have been used to manage maize weevils, but their prolonged application has been associated with environmental contamination, pesticide resistance, and adverse health effects in humans and animals. These challenges have inspired the search for safe, eco-friendly, and bioactive alternatives from natural sources. Citrus plants are among the most widely consumed fruits globally, with their peels and leaves constituting a significant proportion of agricultural waste. These waste products are rich in essential oils, particularly limonene, which has demonstrated potent insecticidal properties against maize weevils. Repurposing citrus waste into biopesticides offers a sustainable strategy for mitigating maize weevil infestations, thereby reducing postharvest maize losses and enhancing food safety and security. This review examines the prospects of citrus limonene in the development of safe and effective maize weevil biopesticides, highlighting its major chemical constituents, biological activities, and mechanisms of action. Full article
(This article belongs to the Section Crop Protection, Diseases, Pests and Weeds)
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28 pages, 5094 KB  
Review
Mixed Lymphocyte Reaction: Functional Immune Profiling in Transplantation and Beyond
by Nurtilek Galimov, Aruzhan Asanova, Sholpan Altynova and Aidos Bolatov
Diagnostics 2026, 16(6), 929; https://doi.org/10.3390/diagnostics16060929 - 20 Mar 2026
Abstract
The mixed lymphocyte reaction (MLR) is a classic functional assay that models in vitro interactions between responder T cells and allogeneic antigen-presenting cells (APCs). It quantifies the magnitude and quality of alloreactivity, integrating signals from allorecognition, co-stimulation, inflammatory context, and minor histocompatibility antigens [...] Read more.
The mixed lymphocyte reaction (MLR) is a classic functional assay that models in vitro interactions between responder T cells and allogeneic antigen-presenting cells (APCs). It quantifies the magnitude and quality of alloreactivity, integrating signals from allorecognition, co-stimulation, inflammatory context, and minor histocompatibility antigens that may not be captured by molecular matching alone. This review is narrative in nature and is intended as a practical, non-systematic synthesis of the field. To provide a modern, practice-oriented synthesis of MLR designs, readouts, and translational uses, highlighting how new technologies have expanded MLR from bulk proliferation into multidimensional immune profiling.We summarize why MLR remains valuable as a functional compatibility probe beyond HLA typing, including the high baseline frequency of alloreactive T cells that produces robust signals without priming. We then review key design options (one-way vs. two-way formats; stimulator inactivation; responder definition; APC source and maturation) and how these choices affect interpretation for rejection and graft-versus-host disease risk modeling, tolerance-focused studies, and immunomodulatory screening. Next, we outline major readouts—radiometric and flow cytometric proliferation (dye dilution, Ki-67), cytokine/chemokine profiling, cytotoxicity adaptations, and next-generation add-ons (e.g., scRNA-seq, TCR sequencing)—emphasizing complementary strengths and common pitfalls. Finally, we consolidate practical quality and reproducibility controls (donor variability, dynamic range, timing, batch effects, and acceptance criteria) to improve cross-study comparability and translational readiness. Modern MLR platforms combine controllable allogeneic stimulation with scalable, high-resolution readouts for mechanistic discovery, immune monitoring and translational immune profiling. Standardized modular design and rigorous quality control can improve reproducibility and support broader adoption across transplantation, immunotherapy, and immune-modulation research. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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98 pages, 9889 KB  
Systematic Review
Rethinking Education on Critical Infrastructure Resilience and Risk Management: Insights from a Systematic Review
by Francesca Maria Ugliotti, Michele Zucco and Muhammad Daud
Sustainability 2026, 18(6), 3067; https://doi.org/10.3390/su18063067 (registering DOI) - 20 Mar 2026
Abstract
The growing complexity and interdependence of critical infrastructures (CIs), increasingly exposed to natural and technological hazards, call for educational approaches to enhance resilience and risk management. This study examines trends, patterns, and challenges in integrating digital and immersive technologies into education and training [...] Read more.
The growing complexity and interdependence of critical infrastructures (CIs), increasingly exposed to natural and technological hazards, call for educational approaches to enhance resilience and risk management. This study examines trends, patterns, and challenges in integrating digital and immersive technologies into education and training for stakeholders in critical infrastructure management. A systematic review of peer-reviewed literature was conducted using Scopus as the primary source, covering the last decade and analyzing the corpus across six dimensions: technological approach, pedagogical model, hazard typology, infrastructure domain, stakeholder category, and implementation phase. Following the PRISMA framework, 5635 records were identified and screened through a multistage process combining rule-based filtering and manual review, resulting in 105 papers meeting the inclusion criteria. The analysis reveals a shift from classroom instruction and physical drills toward immersive, simulation-based, and data-informed learning ecosystems that strengthen situational awareness, procedural accuracy, and decision-making under stress. However, the review identifies persistent gaps in evaluation metrics, cross-sector frameworks, and collaborative learning environments that limit adoption. The findings underscore that digital and immersive technologies can reconfigure education and training frameworks, enabling the formation of Resilient Operators endowed with adaptive cognition, continuous learning capacities, and responsiveness to natural hazard-induced technological risks. Full article
(This article belongs to the Special Issue Sustainable Disaster Risk Management and Urban Resilience)
41 pages, 1814 KB  
Review
Hydrogel Development, Processing and Applications in Agriculture: A Review
by Carmen Mª. Granados-Carrera, Victor M. Perez-Puyana, Mercedes Jiménez-Rosado and Alberto Romero
Gels 2026, 12(3), 259; https://doi.org/10.3390/gels12030259 (registering DOI) - 20 Mar 2026
Abstract
Hydrogels have emerged as promising functional materials for improving water management and nutrient delivery in agriculture, particularly under conditions of increasing water scarcity and declining soil fertility. However, most commercially available superabsorbent hydrogels are based on petroleum-derived polymers, raising concerns regarding their persistence [...] Read more.
Hydrogels have emerged as promising functional materials for improving water management and nutrient delivery in agriculture, particularly under conditions of increasing water scarcity and declining soil fertility. However, most commercially available superabsorbent hydrogels are based on petroleum-derived polymers, raising concerns regarding their persistence in soils, potential microplastic formation and long-term environmental impact. In response, significant research efforts are being directed toward the development of biodegradable hydrogels derived from renewable biopolymers. This review provides a critical overview of recent advances in hydrogel systems designed for agricultural applications, with a particular focus on biopolymer-based materials. First, the current landscape of hydrogel technologies used as soil conditioners and controlled-release systems for agrochemicals is contextualized, highlighting the limitations of conventional synthetic hydrogels. Subsequently, the main classes of natural polymers explored for hydrogel fabrication, including polysaccharides (e.g., chitosan, alginate, cellulose and starch) and proteins (e.g., gelatin, keratin and soy protein), are analyzed in terms of raw material sources, gelation mechanisms and structure–property relationships. Their performance in key agricultural functions, such as water retention, controlled nutrient release, soil conditioning and enhancement of plant growth, is also discussed. Finally, the review identifies major challenges that currently hinder large-scale implementation, including mechanical stability, degradation behavior in complex soil environments, nutrient release control and economic scalability. By integrating recent progress and outlining emerging research directions, this work aims to support the rational design of next-generation biodegradable hydrogels capable of contributing to sustainable agriculture and circular bioeconomy strategies. Full article
(This article belongs to the Special Issue Innovative Gels: Structure, Properties, and Emerging Applications)
30 pages, 21234 KB  
Article
Analysis of Spatio-Temporal Evolution and Driving Mechanism of Landscape Pattern in Huangshan City Based on Moving Window Method and Geodetector
by Enyuan Yu, Qian Wang, Honggang Zheng, Yifei Pan, Yuxi Liu, Qizhi Cao, Yufeng Gao and Xingfeng Zhao
Land 2026, 15(3), 503; https://doi.org/10.3390/land15030503 - 20 Mar 2026
Abstract
The spatiotemporal evolution of landscape patterns represents the most direct manifestation of land use change and remains a pivotal focus within landscape ecology research. Taking Huangshan City—a typical mountainous tourism city—as the study area, this research systematically analyzes the spatiotemporal evolution characteristics and [...] Read more.
The spatiotemporal evolution of landscape patterns represents the most direct manifestation of land use change and remains a pivotal focus within landscape ecology research. Taking Huangshan City—a typical mountainous tourism city—as the study area, this research systematically analyzes the spatiotemporal evolution characteristics and driving mechanisms of landscape patterns over the past three decades. Based on land use data from 1992, 2002, 2012, and 2022, the study employs an integrated methodological framework including land use transition matrices, landscape pattern indices, moving window analysis, and the geographical detector (Geodetector) model, supported by ArcGIS and FRAGSTATS platforms. The results indicate that (1) during the study period, the landscape structure in Huangshan City exhibited a general trend characterized by “a stable foundation of forest land, continuous contraction of cropland, and significant expansion of construction land.” (2) From 1992 to 2012, cropland served as the primary source of transfer, mainly being converted into forest land; conversely, between 2012 and 2022, the reciprocal transformation between cropland and forest land became the dominant transition process. (3) At the landscape level, overall diversity enhanced and spatial distribution tended toward uniformity, whereas landscape fragmentation persisted in localized areas. (4) The driving force analysis revealed that “distance to the urban center” was the primary driving factor shaping landscape pattern changes, with its explanatory power continuously increasing. Furthermore, significant synergistic enhancement effects were observed between natural and socio-economic factors. These findings provide a scientific basis for ecological protection, restoration, and sustainable development strategies in Huangshan City within the context of rapid urbanization and tourism development. Full article
13 pages, 2559 KB  
Article
Hydrothermal Extraction and Characterization of Cellulose Fibers from Bamboo Moso (Phyllostachys edulis) Culms
by Andrea Marangon, Elisa Calà, Alessandro Bessi, Alessandro Croce, Enrico Avattaneo, Eleonora Cara and Giorgio Gatti
Fibers 2026, 14(3), 38; https://doi.org/10.3390/fib14030038 - 20 Mar 2026
Abstract
In recent years, there has been a notable increase in commercial demand for natural fibers. Consequently, numerous studies have concentrated on formulating innovative industrial production methodologies for natural fibers, with a particular emphasis on the environmental sustainability of production processes. Among natural fiber [...] Read more.
In recent years, there has been a notable increase in commercial demand for natural fibers. Consequently, numerous studies have concentrated on formulating innovative industrial production methodologies for natural fibers, with a particular emphasis on the environmental sustainability of production processes. Among natural fiber sources, bamboo has emerged as a leading candidate, attracting considerable interest due to its exceptional renewability, rapid growth, and low cultivation requirements. The contemporary industrial methodologies employed in the extraction of cellulose from bamboo frequently entail the utilization of concentrated solutions of strong acids and bases, often at elevated temperatures and with extended treatment durations. These processes generate highly polluting waste from mineral acids and bases, posing significant environmental challenges and ecosystem damage. In response to the prevailing concerns, there has been a marked increase in the focus on environmentally friendly techniques that combine enzymatic treatments, selective chemical reagents, and optimized mechanical processes. These processes facilitate the extraction of high-quality bamboo fibers, which are suitable for utilization in the textile industry and have the potential to replace synthetic fibers. This work demonstrates the efficacy of methodologies employing more diluted solutions than conventional approaches. Specifically, this study utilizes a weak base, such as NH4OH, in conjunction with hydrothermal extraction. It is therefore possible for dilute weak base solutions to yield natural fibers after a relatively brief period of processing, typically just a few hours. Full article
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21 pages, 281 KB  
Review
Citation Inaccuracies and the Need for Multi-Level Oversight in AI-Assisted Medical Writing
by Vaikunthan Rajaratnam, Usama Farghaly Omar, Kristen Kee and Arun-Kumar Kaliya-Perumal
Standards 2026, 6(1), 10; https://doi.org/10.3390/standards6010010 - 20 Mar 2026
Abstract
Generative artificial intelligence (AI)-based large language models (LLMs) are increasingly being used in medical writing to improve efficiency and broaden access to knowledge. However, concerns have emerged regarding the accuracy of the citations they generate. This review discusses the issue of citation inaccuracies [...] Read more.
Generative artificial intelligence (AI)-based large language models (LLMs) are increasingly being used in medical writing to improve efficiency and broaden access to knowledge. However, concerns have emerged regarding the accuracy of the citations they generate. This review discusses the issue of citation inaccuracies in AI-assisted medical writing and its implications for scientific reliability and accountability in academic medicine. Published literature describing citation errors in AI-generated content, particularly in medical and academic contexts, was examined to understand the nature and persistence of this problem and to consider potential safeguards. Reports consistently describe citation inaccuracies, including fabricated references, incorrect bibliographic details, and incomplete source information such as missing authors, journal titles, publication years, or digital object identifiers. Although these tools continue to evolve, such errors remain reported and highlight limitations in their reliability. While LLMs offer clear benefits in supporting medical writing, their outputs require careful verification. As developers continue to address these challenges, responsible use will depend on continued human oversight, improved transparency, greater user awareness, and institutional and policy-level guidance to ensure accurate and trustworthy use of generative AI in medical writing. Full article
15 pages, 1747 KB  
Article
Nitrogen Oxide Emissions as a Proxy for Simplifying Large-Scale Emission Inventories and Tracking Decarbonization
by Banyan Lehman and Bill Van Heyst
Atmosphere 2026, 17(3), 320; https://doi.org/10.3390/atmos17030320 - 20 Mar 2026
Abstract
Decarbonizing energy production is critical to slowing the effects of climate change and furthering global sustainability. Progress is often gauged via carbon dioxide (CO2) emissions; however, sources of CO2 vary beyond combustion, presenting a significant challenge to accurate tracking due [...] Read more.
Decarbonizing energy production is critical to slowing the effects of climate change and furthering global sustainability. Progress is often gauged via carbon dioxide (CO2) emissions; however, sources of CO2 vary beyond combustion, presenting a significant challenge to accurate tracking due to these various sources and sinks and the ubiquitous nature of CO2 in the atmosphere. Nitrogen oxide (NOX) emissions have previously been proposed as a surrogate for tracking sustainability, as they are primarily released from combustion processes. Facility-level data from Canada’s National Pollutant Release Inventory and Greenhouse Gas Reporting Program over a six-year period is used to assess the correlation between NOX and CO2 emissions from integrated facilities across Canada. Combustion-related CO2 emissions accounting for approximately 94% of Canadian industrial emissions are examined, targeting eleven industries which together encompass over 90% of combustion emissions. Multiple linear regressions (MLRs) on each industry correlating NOX, CO2, and the inventory methods used (i.e., emission factors (EFs), source monitoring, mass balance, engineering estimates, and speciation) show R2 values ranging from 0.81 to 0.96 for all but one industry. Several industries indicate that the methods used to calculate emissions influence the correlation of CO2 to NOX, highlighting issues in the current inventory techniques. The NOX-to-CO2 ratios calculated for the integrated facilities are similar to the ratios of the published main process-level EFs for NOX to CO2 (where available). These MLR models on NOX could be used to predict CO2 emissions with relative ease and accuracy in other jurisdictions, thereby simplifying large-scale emission inventory compilation while tracking sustainability. Full article
(This article belongs to the Special Issue Emission Inventories and Modeling of Air Pollution)
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23 pages, 630 KB  
Article
Depth-First Search-Based Malicious Node Detection with Honeypot Technology in Wireless Sensor Networks
by Sercan Demirci, Doğan Yıldız, Durmuş Özkan Şahin and Asmaa Alaadin
Mathematics 2026, 14(6), 1050; https://doi.org/10.3390/math14061050 - 20 Mar 2026
Abstract
Wireless sensor networks (WSNs) are highly susceptible to Denial-of-Service (DoS) attacks due to their resource-constrained and distributed nature. In this study, we propose a novel trust-based malicious node detection mechanism that leverages a Depth-First Search (DFS) strategy to trace and identify attack sources [...] Read more.
Wireless sensor networks (WSNs) are highly susceptible to Denial-of-Service (DoS) attacks due to their resource-constrained and distributed nature. In this study, we propose a novel trust-based malicious node detection mechanism that leverages a Depth-First Search (DFS) strategy to trace and identify attack sources within clustered WSN architectures efficiently. The proposed approach dynamically evaluates trust scores between nodes to detect anomalous behaviors and employs a honeypot-based redirection system to isolate compromised nodes from the main communication flow. This combination enhances detection accuracy while minimizing false positives and energy overhead. The method is implemented and evaluated using a custom simulation environment. Comparative experimental results against state-of-the-art techniques such as the Evolved Trust Updating Mechanism (EVO) and Multi-agent Trust-based Intrusion Detection System (MULTI) demonstrate that our Trust-Based Honeypot (TBHP) achieves superior performance in terms of detection rate, false-alarm rate, and network lifetime extension. Full article
(This article belongs to the Topic Recent Advances in Security, Privacy, and Trust)
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20 pages, 1640 KB  
Article
Cinnamon Bark Essential Oil as a Natural Plant Protection Agent: Chemical Profile, Antimicrobial Activity, and Defence Induction
by Elżbieta Gębarowska, Karolina Budek, Martyna Gębarowska, Anna Kmieć and Antoni Szumny
Molecules 2026, 31(6), 1036; https://doi.org/10.3390/molecules31061036 - 20 Mar 2026
Abstract
Ceylon cinnamon (Cinnamomum verum J. Presl) bark essential oil (CBO) represents a promising source of natural bioactive compounds for biological plant protection. For the first time, the antibacterial and antifungal activity of CBO was systematically evaluated against a curated panel of phytopathogenic [...] Read more.
Ceylon cinnamon (Cinnamomum verum J. Presl) bark essential oil (CBO) represents a promising source of natural bioactive compounds for biological plant protection. For the first time, the antibacterial and antifungal activity of CBO was systematically evaluated against a curated panel of phytopathogenic strains (IOR collection), revealing broad-spectrum efficacy across both bacteria and filamentous pathogens. This study evaluated its chemical composition, antimicrobial activity against phytopathogens, effects on bacterial metabolic activity, and its ability to induce plant defence responses. CBO was dominated by cinnamaldehyde, linalool, and eucalyptol. The oil exhibited strong antibacterial activity against Dickeya dadantii, Pectobacterium carotovorum, Pseudomonas syringae, and Xanthomonas hortorum as well as antifungal activity against Fusarium graminearum, F. culmorum, Rhizoctonia solani and Phytophthora cinnamomi. Metabolic assays revealed a marked reduction in bacterial metabolic activity, indicating that CBO disrupts physiological processes and inhibits growth. In planta experiments showed that foliar application of CBO stimulated PAL activity in wheat leaves without visible phytotoxic symptoms. These findings demonstrate a multifunctional mode of action of CBO, combining direct antimicrobial effects with the elicitation of plant defence responses, and support its potential application in sustainable crop protection. Full article
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17 pages, 5909 KB  
Article
Preliminary Anti-Melanoma Activity of a Chlorogenic Acid-Based PROTAC Targeting MDM4, a Candidate Protein Identified by Proteomics
by Zhiting Mei, Jiali Sun, Pengfei Zhao, Yiming Luo, Jine Niu and Danfei Huang
Foods 2026, 15(6), 1082; https://doi.org/10.3390/foods15061082 - 19 Mar 2026
Abstract
Chlorogenic acid (CGA), which is ubiquitous in diverse botanical sources, demonstrates considerable anticancer potential through modulation of multiple targets or signaling pathways, thereby posing substantial challenges for mechanistic elucidation and target identification. Based on the proteolysis targeting chimera (PROTAC) technology’s ability to induce [...] Read more.
Chlorogenic acid (CGA), which is ubiquitous in diverse botanical sources, demonstrates considerable anticancer potential through modulation of multiple targets or signaling pathways, thereby posing substantial challenges for mechanistic elucidation and target identification. Based on the proteolysis targeting chimera (PROTAC) technology’s ability to induce targeted protein degradation via ubiquitin-proteasome pathway recruitment, we synthesized a panel of CGA-PROTACs. These compounds incorporated the natural product CGA as the target-binding ligand, conjugated to pomalidomide (an E3 ligase-recruiting moiety) via various synthetic linkers. The findings indicated that compound A7, linked with an alkane linker, exhibited a notable anti-proliferative effect on 4T1 and A375 cells in vitro. The IC50 value of A7 on A375 cells reached 69.70 μM, which is 2.2 times better than the effect of the precursor compound CGA (IC50 = 148.80 μM). Mouse double minute 4 (MDM4) was confirmed as a potential target of compound A7 through a combination of proteomics, Western blot analysis and molecular dynamics simulation. CGA-PROTAC A7 treatment led to a dose-dependent reduction in MDM4 protein levels while significantly upregulating p53 and p21 protein expression, and thus inhibited proliferation, induced G2/M phase cell cycle arrest, and markedly enhanced apoptosis in melanoma A375 cells. This study successfully applied an effective strategy for target identification and medication discovery of natural compounds. In addition, CGA-PROTAC A7 was synthesized in one step with an overall yield of 45.96%, providing a feasible route for synthesis and establishing a basis for the combination of natural product polyphenols with PROTAC technology. Full article
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21 pages, 2334 KB  
Review
Exploring Microalgae as a Novel Resource for Hepatocellular Carcinoma Therapy
by Sik Yoon, Kok Keong Tan, Won Hoon Song, Chang Won Kim, Boon Huat Bay and Sae-Ock Oh
Molecules 2026, 31(6), 1033; https://doi.org/10.3390/molecules31061033 - 19 Mar 2026
Abstract
Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality in the world. Although there is an armamentarium of therapeutic options available for HCC therapy, current treatment modalities still face challenges, such as limited effectiveness and resistance to therapy due to inherent intratumoral [...] Read more.
Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality in the world. Although there is an armamentarium of therapeutic options available for HCC therapy, current treatment modalities still face challenges, such as limited effectiveness and resistance to therapy due to inherent intratumoral heterogeneity. Hence, the development of novel therapeutics is an unmet need. Microalgae possess the ability to provide naturally derived compounds that are attractive for biomedical applications. The multifunctional nature of microalgae, with its unique combination of anticancer metabolites, oxygen-generating capability, and photosensitizing activity, make them a versatile platform for developing next-generation cancer therapeutics. In light of the above, this succinct narrative review highlights the potential biomedical applications of microalgae in cancer therapy, with a focus on HCC. Preclinical studies have shown the significant potential of microalgae as naturally occurring sources of chemopreventive and anticancer agents against HCC. Future directions include the use of biotechnology to enhance the production of microalgal-derived bioactive compounds and the formulation of biocompatible and biodegradable drug–microalgae embolic agents with prolonged release of anticancer drugs, thereby giving rise to synergistic antitumor effects, and their application for the delivery of immune checkpoint inhibitors for immunotherapy in HCC. Overall, microalgae hold considerable promise for advancing innovative therapeutic strategies against HCC. Full article
(This article belongs to the Special Issue Natural Compounds in Modern Therapies, 3rd Edition)
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