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18 pages, 2128 KB  
Article
Effects of Dietary Squalene Supplementation on the Growth Performance and Disease Resistance of Largemouth Bass
by Shan Liu, Mengmeng Chen, Yan Meng, Mingyang Xue, Yong Zhou, Liping Zhang, Peng Chen, Yuding Fan, Yazhen Yang and Zhenyu Huang
Vet. Sci. 2026, 13(5), 448; https://doi.org/10.3390/vetsci13050448 - 1 May 2026
Abstract
Feed supplements play a crucial role in improving and maintaining fish health in modern aquaculture practices. Squalene is a functional lipid naturally present in fatty tissues, possessing numerous beneficial biological properties and wide applications in the food and pharmaceutical industries. In this study, [...] Read more.
Feed supplements play a crucial role in improving and maintaining fish health in modern aquaculture practices. Squalene is a functional lipid naturally present in fatty tissues, possessing numerous beneficial biological properties and wide applications in the food and pharmaceutical industries. In this study, the effects of 100 mg/kg (S1), 200 mg/kg (S2), 300 mg/kg (S3), and 400 mg/kg (S4) of dietary squalene supplementation over four weeks on growth performance, antioxidation, hepatoprotection, hypoxia tolerance, immune relative genes expression, and disease resistance of largemouth bass (Micropterus salmoides) were assessed. The results showed that squalene supplementation significantly increased the weight gain rate (WGR) and specific growth rate (SGR) of largemouth bass (p < 0.05). Serum glucose (GLU) levels were significantly decreased in all squalene-supplemented groups (p < 0.05). Squalene supplementation had minimal effect on serum triglyceride (TG) and total cholesterol in (TCHO) levels. A decrease in malondialdehyde (MDA) level, but accompanied by increases in superoxide dismutase (SOD) and hepatic catalase (CAT) activities, was observed in the S1 group supplemented with squalene. These suggest that squalene may mitigate free radical damage and promote health in largemouth bass. Dietary squalene supplementation enhanced intestinal enzyme activities (trypsin, lipase, and α-amylase) in largemouth bass without inducing any apparent hepatic or histopathological alterations. Squalene supplementation improved hypoxia tolerance and antiviral gene expression (mx, ifn-γ, and irf3) while suppressing the expression of inflammatory cytokine (il-1β, il-8, and tnf-α). The survival rate following LMBRaV infection was significantly higher in the S1 group (100 mg/kg group) compared to the control (p < 0.05). In conclusion, this study demonstrated that adding squalene into the diet of largemouth bass at an optimal level of 100 mg/kg effectively promotes growth performance, enhances digestive enzyme activity and hypoxia tolerance, and modulates lipid metabolism and immune gene expression, thereby contributing to improved resistance against LMBRaV. These findings confirm that squalene can serve as a beneficial functional feed additive in aquaculture. Full article
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17 pages, 313 KB  
Article
The Oxidative Stress Imbalance in Children and Adults with IBD and Associated Factors
by Sara Quattrini, Tiziana Galeazzi, Chiara Monachesi, Alessandra Palpacelli, Giulia Catassi, Claudia Quatraccioni, Giulia Annulli, Antonio Di Sario, Laura Cianfruglia, Monia Orciani, Tatiana Armeni, Andrea Faragalli, Rosaria Gesuita, Maria Elena Lionetti, Carlo Catassi and Simona Gatti
Nutrients 2026, 18(9), 1458; https://doi.org/10.3390/nu18091458 - 1 May 2026
Abstract
Background/Objectives: An imbalance in oxidative stress (OS) has been implicated in the pathogenesis of Inflammatory Bowel Disease (IBD). We compared OS status in IBD children and adults versus healthy controls by exploring variables impacting the OS disruption in IBD. Methods: Total [...] Read more.
Background/Objectives: An imbalance in oxidative stress (OS) has been implicated in the pathogenesis of Inflammatory Bowel Disease (IBD). We compared OS status in IBD children and adults versus healthy controls by exploring variables impacting the OS disruption in IBD. Methods: Total antioxidant capacity (ferric-reducing ability of plasma (FRAP)), reactive species (ROS), oxidative products (advanced oxidation protein products (AOPPs) and thiobarbituric acid reactive substances (TBARSs)), and antioxidant defenses (glutathione, GSH and intracellular activity of the main antioxidant enzymes) were evaluated. Correlations between OS markers, clinical features, disease characteristics, and inflammatory indices were explored. Results: Eighty-two IBD patients (67.5% in clinical remission) and 73 healthy subjects were enrolled. IBD children showed significant FRAP reduction compared to controls and IBD adults (p < 0.0001), increased AOPPs and reduced GSH compared to controls (p < 0.0001 and p = 0.0011, respectively), higher total GSH (p = 0.020), and lower TBARSs (p = 0.023) compared to IBD adults. In the pediatric group, FRAP was significantly reduced in those with IBD and increased in older subjects and males, while AOPP levels were positively affected by increasing age. In the total IBD cohort, higher FRAP was associated with male gender, increasing age, overweight, and mesalazine therapy. The diagnosis of Ulcerative Colitis was associated with lower FRAP and AOPP levels compared to Crohn’s disease. Increased fecal calprotectin significantly decreased the total antioxidant capacity. Conclusions: The antioxidant system shows significant differences in IBD compared to controls, particularly in the pediatric group. The observed pediatric–adult pattern may suggest age-related differences in oxidative balance, but these findings should be interpreted with caution, given the modest sample size. Clinical Trial Registration Number: NCT04513015. Full article
(This article belongs to the Special Issue Nutritional Support and Care for Pediatric Gastroenterology)
22 pages, 2108 KB  
Review
Epigenetic Regulation of Hyaluronan-Associated Genes in the Brain: Identifying Key Regulatory Sites
by Rosalyn E. Acevedo, Esther Walton and Karen R. Mifsud
Epigenomes 2026, 10(2), 28; https://doi.org/10.3390/epigenomes10020028 - 1 May 2026
Abstract
Hyaluronan (HA) is a ubiquitous extracellular matrix (ECM) component that is gaining significant attention for its diverse roles in cell signalling and disease. The biological functions of HA are dependent on its molecular weight (Mw): low Mw polysaccharide chains drive [...] Read more.
Hyaluronan (HA) is a ubiquitous extracellular matrix (ECM) component that is gaining significant attention for its diverse roles in cell signalling and disease. The biological functions of HA are dependent on its molecular weight (Mw): low Mw polysaccharide chains drive stimulatory processes such as inflammation and angiogenesis, whereas high Mw HA is stabilising and anti-inflammatory. Growing evidence indicates that HA is integral to brain function. The composition of HA in the brain is regulated by the balance of enzymatic synthesis and degradation, mediated by different isoforms of hyaluronan synthase (HAS) and hyaluronidase (HYAL) respectively. Fluctuating expression of the genes encoding the HAS and HYAL enzymes has been implicated in neuropathology and ageing, with some studies providing evidence towards epigenetic regulation of these genes. The regulatory environment of the brain confers a unique balance of enhanced protection alongside the requirement for maximum flexibility. This scoping review focuses on summarising current knowledge regarding epigenetic regulation of HAS and HYAL genes in neural contexts, as well as identifying gaps in knowledge against which future research can be directed. Understanding how these genes are regulated, particularly through epigenetic mechanisms, provides insight into how HA is regulated in the brain, facilitating understanding regarding its function in brain health and disease. Full article
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20 pages, 14545 KB  
Article
Phylogenetic Distribution and Predicted Functional and Ecological Shifts in Soil Bacterial Communities Along a Soda Saline–Alkali Wetland Degradation Gradient
by Junnan Ding, Xue Cong and Xin Li
Life 2026, 16(5), 760; https://doi.org/10.3390/life16050760 - 1 May 2026
Abstract
Wetland degradation in soda saline–alkali ecosystems can profoundly alter belowground microbial communities, yet its effects on bacterial phylogenetic distribution and predicted ecological characteristics remain insufficiently understood. This study investigated soil physicochemical properties, enzyme activities, and bacterial communities across a wetland degradation gradient in [...] Read more.
Wetland degradation in soda saline–alkali ecosystems can profoundly alter belowground microbial communities, yet its effects on bacterial phylogenetic distribution and predicted ecological characteristics remain insufficiently understood. This study investigated soil physicochemical properties, enzyme activities, and bacterial communities across a wetland degradation gradient in the Halahai Provincial Nature Reserve, China, including reed wetland (RW), meadow steppe (MS), and degraded Suaeda saline patches (DS). Soil analyses were integrated with 16S rRNA gene amplicon sequencing, phylogenetic reconstruction, and FAPROTAX and BugBase prediction. DS showed significantly higher pH and electrical conductivity, but lower soil water content, organic carbon, nutrient availability, and urease activity than RW and MS. Alpha diversity analysis indicated that DS had lower bacterial richness and diversity, but higher dominance, whereas RW and MS did not differ significantly. Beta-diversity analysis revealed clear habitat-dependent separation, with DS harboring the most distinct community structure. Taxonomic and phylogenetic analyses indicated enrichment of Gemmatimonadota and the RCP2-54 lineage in DS, whereas RW and MS were more strongly associated with Pseudomonadota, Acidobacteriota, and related groups. Predicted functional and phenotypic analyses further suggested a shift toward stress-related and degradation-associated traits in DS. These findings demonstrate that wetland degradation reshaped the taxonomic composition, phylogenetic distribution, and predicted ecological characteristics of soil bacterial communities in this fragile ecosystem. Full article
(This article belongs to the Section Diversity and Ecology)
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20 pages, 3789 KB  
Article
Valorization and Functional Enhancement of Mature Assam Tea Leaves Through Indigenous Filamentous Fungi-Based Fermentation for Functional Drink Development
by Kridsada Unban, Punnita Pamueangmun, Nang Nwet Noon Kham, Pratthana Kodchasee, Apinun Kanpiengjai, Chalermpong Saenjum, Kalidas Shetty and Chartchai Khanongnuch
Foods 2026, 15(9), 1562; https://doi.org/10.3390/foods15091562 - 1 May 2026
Abstract
Miang, a traditional fermented tea produced from Camellia sinensis var. assamica, is of notable cultural and socio-economic relevance in Northern Thailand. Traditionally, the non-filamentous fungi-based process (NFP) in western Lanna uses only young tea leaves, resulting in substantial amounts of mature leaves [...] Read more.
Miang, a traditional fermented tea produced from Camellia sinensis var. assamica, is of notable cultural and socio-economic relevance in Northern Thailand. Traditionally, the non-filamentous fungi-based process (NFP) in western Lanna uses only young tea leaves, resulting in substantial amounts of mature leaves being discarded as agricultural waste. This study aimed to utilize the mature tea leaves by adapting the filamentous fungi growth-based process (FFP) of eastern Lanna using selected tannin-tolerant microorganisms, including Aspergillus niger MLF3, Cyberlindera rhodanensis P3, and Lactiplantibacillus pentosus A14-6. Study on fermentation dynamics and bioactive compound formation based on a 2-step fermentation process: 3-day solid-state fermentation with A. niger MLF3, followed by 7-day submerged fermentation by co-culture of C. rhodaninsis P3, and L. pentosus A14-6 in 500 mL sterile distilled water at 30 °C. Increased activities of polysaccharide-degrading enzymes and organic acids were clearly observed during solid-state fermentation, while the significant changes in polyphenol, antioxidant, and reducing sugar content in cell-free supernatant (CFS) were found after submerged fermentation. The obtained CFS shows inhibitory effects of 90 ± 2.5% and 95 ± 1.8% on α-glucosidase and α-amylase, respectively. Analysis of CFS by E-tongue and E-nose clearly indicated the influence of microbial mixture on the taste and aroma of the fermented products. These results demonstrate not only a high-yielding strategy for the effective biotransformation of mature tea leaves into functional drink products but also significant implications for reducing agricultural waste. Full article
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21 pages, 1801 KB  
Review
Engineering Carbonic Anhydrase for Enhanced CO2 Capture and Valorization: A Review
by Xin Chen, Xiaofeng Ling, Zhen Xu and Yuanfen Xia
Clean Technol. 2026, 8(3), 63; https://doi.org/10.3390/cleantechnol8030063 - 1 May 2026
Abstract
The continuous increase in atmospheric CO2 concentration exacerbates global climate change, making carbon reduction an urgent global priority. Carbonic anhydrase (CA), a highly efficient biocatalyst that converts CO2 into bicarbonate, demonstrates significant potential for carbon capture and resource utilization. However, the [...] Read more.
The continuous increase in atmospheric CO2 concentration exacerbates global climate change, making carbon reduction an urgent global priority. Carbonic anhydrase (CA), a highly efficient biocatalyst that converts CO2 into bicarbonate, demonstrates significant potential for carbon capture and resource utilization. However, the stability and catalytic efficiency of native CA in industrial environments are limited, particularly its poor thermal tolerance under flue gas conditions and its sensitivity to impurities, hindering its direct large-scale application. This review systematically summarizes recent advances in modifying microbial CA through protein engineering (e.g., directed evolution, rational design) and immobilization techniques, which have markedly enhanced its thermal stability, adaptability, and reusability. Among these, the integration of machine learning with high-throughput experimentation has emerged as a transformative strategy for CA engineering. Furthermore, we outline CA-driven pathways for CO2 conversion into high-value chemicals and bioenergy. Finally, future prospects are discussed, including interdisciplinary integration, computational modeling coupled with experimental validation, and comprehensive life-cycle and techno-economic assessments, to facilitate the scaled application of engineered microbial CA in carbon neutrality pathways. Collectively, this review highlights the critical role of engineered CA in bridging biocatalysis with industrial carbon management, offering a viable and sustainable pathway toward carbon neutrality. Full article
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26 pages, 1967 KB  
Review
Alkaloid-Based Insecticides as Possible Tools for Sustainable Agriculture: Mechanisms, Applications, and Challenges
by Everaldo Attard and Jules Siedenburg
Agrochemicals 2026, 5(2), 22; https://doi.org/10.3390/agrochemicals5020022 - 1 May 2026
Abstract
Alkaloids are structurally diverse, nitrogen-containing plant secondary metabolites with well-documented insecticidal activity. This review examines alkaloid-based insecticides, focusing on their chemical diversity, biosynthetic origins, plant distribution, and physicochemical properties relevant to pest control on farms. The principal molecular targets and modes of action [...] Read more.
Alkaloids are structurally diverse, nitrogen-containing plant secondary metabolites with well-documented insecticidal activity. This review examines alkaloid-based insecticides, focusing on their chemical diversity, biosynthetic origins, plant distribution, and physicochemical properties relevant to pest control on farms. The principal molecular targets and modes of action are discussed, including interactions with nicotinic acetylcholine receptors, acetylcholinesterase, ryanodine receptors, and GABAergic signaling. Another focus is key metabolic enzymes, together with their activity spectra against major agricultural pests. Recent advances in rational structural modification, supported by crystallographic data, computational modeling, and structure–activity relationship studies, are highlighted as strategies to enhance the potency, selectivity, and stability of these compounds. Toxicological profiles, food residue behavior, analytical challenges, and regulatory considerations are critically assessed, emphasizing that natural origin does not equate to inherent safety. The review further evaluates the role of alkaloid-based insecticides within integrated pest management systems and identifies key research gaps related to environmental safety, non-target effects, and regulatory development and harmonization. It concludes that alkaloids are positioned as potentially valuable tools for sustainable agriculture when deployed within science-based regulatory frameworks and integrated control strategies. Full article
(This article belongs to the Topic Natural Products in Crop Pest Management)
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22 pages, 4037 KB  
Article
Diversified Crop Rotation Enhances Soil Health and Microbial Diversity in Successive Maize Cropping on Sodic Soils
by Yule Sun, Haiwen Duan, Lanying Zhang, Shanshan Zhu, Qiang Li, Yang Zhou, Meiying Liu, Jicheng Tai, Yupeng Jing and Xiaofang Yu
Agriculture 2026, 16(9), 997; https://doi.org/10.3390/agriculture16090997 - 30 Apr 2026
Abstract
Intensive monoculture exacerbates soil compaction and sodification in the West Liao River Plain. This study evaluated legacy effects of diversified 3-year rotations on sodic soil health (ESP > 15%, ECe < 4 dS m−1) during two subsequent maize seasons. Rotations incorporating [...] Read more.
Intensive monoculture exacerbates soil compaction and sodification in the West Liao River Plain. This study evaluated legacy effects of diversified 3-year rotations on sodic soil health (ESP > 15%, ECe < 4 dS m−1) during two subsequent maize seasons. Rotations incorporating salt-tolerant forages and deep-rooted crops (sugar beet–Echinochloa–sorghum and Echinochloa–tall fescue–silage corn) significantly reduced bulk density (8.6–13.1%) and exchangeable sodium percentage (up to 14.1 percentage points) relative to continuous monoculture. Treatments with maximum desalination (22.6% reduction) enhanced fungal α-diversity by 98.0%, while forage-dominated systems enriched Acidobacteriota by 35.2%, shifting bacterial communities toward oligotrophic dominance. Structural equation modeling confirmed that rotation effects on enzyme activity were mediated through reduced bulk density and ESP. These systems provide effective biological models for sustainable maize cultivation in sodic soils via synergistic physical-chemical-biological amelioration. Full article
(This article belongs to the Section Agricultural Soils)
19 pages, 622 KB  
Article
Harmonizing Perspectives on MPS II Care in Türkiye: A Delphi Study Towards Treatment Management Consensus
by Neslihan Onenli Mungan, Leyla Tumer, Serap Sivri, Nur Arslan, Sema Kalkan Ucar, Berna Seker Yilmaz and Gulden Gokcay
Healthcare 2026, 14(9), 1214; https://doi.org/10.3390/healthcare14091214 - 30 Apr 2026
Abstract
Background: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the iduronate-2-sulfatase gene, leading to progressive multisystem involvement. Although international management guidelines exist, challenges in their implementation across different healthcare systems remain insufficiently [...] Read more.
Background: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the iduronate-2-sulfatase gene, leading to progressive multisystem involvement. Although international management guidelines exist, challenges in their implementation across different healthcare systems remain insufficiently addressed. This study aimed to establish a national expert consensus in Türkiye on the treatment and management of MPS II, aligning local practice with international standards. Methods: A modified Delphi methodology was conducted using two rounds of online surveys supported by three steering committee meetings. The process involved 10 experienced clinicians and a scientific committee of six professors. Based on international guidelines and country-specific clinical challenges, 72 consensus statements and 84 exploratory questions were developed. Statements achieving ≥ 80% agreement were accepted as consensus. Results: Consensus supported initiating enzyme replacement therapy (ERT) in both severe and attenuated MPS II, guided by functional and cognitive status. Severe cognitive impairment was not considered an exclusion criterion for ERT, given its somatic benefits. Experts agreed on continuing ERT into adulthood with individualized discontinuation decisions. Routine evaluations every 6–12 months, including respiratory, cardiac, and neurocognitive assessments, were recommended. Additional consensus areas included individualized premedication strategies, structured transition to adult care, selective home infusion, annual patient-reported outcome assessments, and the establishment of a national MPS II registry. Hematopoietic stem cell transplantation was not endorsed. Conclusions: This Delphi study demonstrates strong expert consensus on MPS II management in Türkiye, providing a practical framework to guide clinical practice, support alignment with international recommendations, and inform future policy and research priorities. Full article
17 pages, 979 KB  
Article
Primary Succession Shifts Fine-Root Nutrient Acquisition from Morphological Capture to Rhizosphere-Mediated Biochemical Mobilization
by Qiao Gao, Gang Xu, Yi Hu, Meiyu Liu, Xuyang Lu and Baoli Duan
Forests 2026, 17(5), 555; https://doi.org/10.3390/f17050555 - 30 Apr 2026
Abstract
Primary succession following glacier retreat provides a natural system for testing whether soil development simply shifts fine roots along a single acquisitive–conservative axis orinstead changes the nutrient-acquisition pathway that dominates at the community level. We hypothesized a stage-dependent sequence, from substrate-limited exploration, to [...] Read more.
Primary succession following glacier retreat provides a natural system for testing whether soil development simply shifts fine roots along a single acquisitive–conservative axis orinstead changes the nutrient-acquisition pathway that dominates at the community level. We hypothesized a stage-dependent sequence, from substrate-limited exploration, to transient morphological capture, and finally to rhizosphere-mediated biochemical mobilization. To test this idea, we quantified fine-root morphology, absorptive-transport partitioning, anatomy, phosphatase activity, exudation, community-scale belowground structure, and soil and rhizosphere properties across woody communities representing approximately 20, 40, and 90 years since deglaciation in the Hailuogou Glacier foreland. Across succession stages, bulk density and pH declined, whereas field capacity, soil carbon, and soil nitrogen increased, indicating rapid development of the belowground resource environment. Fine-root strategies did not fall along a single acquisitive–conservative continuum. Instead, morphological nutrient capture peaked at intermediate succession: the 40-year stage had the highest specific root length, specific root area, absorptive-to-transport root length ratio, and root nitrogen concentration. In contrast, the 90-year stage showed lower specific root length but higher dry matter content, thicker cortex, greater standing fine-root biomass, larger rhizosphere volume, higher phosphatase activity, and greater area-based carbon exudation. This late-successional syndrome coincided with stronger extracellular enzyme activity, larger dissolved organic carbon and nitrogen pools, and higher microbial biomass, despite negative net nitrogen mineralization. Species-level analyses showed that biochemical-input traits were jointly shaped by successional stage, species identity, and their interaction. Together, these results show that primary succession did not simply increase or decrease root acquisitiveness. Instead, as soils developed, it changed the nutrient-acquisition pathway that dominated, with direct implications for nutrient cycling and vegetation dynamics in rapidly developing glacier-foreland ecosystems. Full article
(This article belongs to the Section Forest Soil)
30 pages, 2553 KB  
Article
Exploring Neuroprotective Potential of Bioactive Compounds Obtained from Artichoke By-Products by Pressurized Liquid Extraction via Response Surface Methodology
by Edmondo Messinese, Alberto Valdés, Antonella Cavazza and Alejandro Cifuentes
Int. J. Mol. Sci. 2026, 27(9), 4059; https://doi.org/10.3390/ijms27094059 - 30 Apr 2026
Abstract
Artichoke by-products (ABP) represent valuable sources of bioactive compounds with relevant health benefits. In this study, a green extraction strategy based on pressurized liquid extraction (PLE) was optimized to enhance the recovery of phenolic and flavonoid compounds from ABP using a response surface [...] Read more.
Artichoke by-products (ABP) represent valuable sources of bioactive compounds with relevant health benefits. In this study, a green extraction strategy based on pressurized liquid extraction (PLE) was optimized to enhance the recovery of phenolic and flavonoid compounds from ABP using a response surface methodology. Extraction temperature and solvent composition were identified as the key factors driving extraction performance. Optimal conditions using a mixture of ethyl acetate and ethanol (90/10, v/v) at 180 °C significantly enhanced extraction yield, total phenolic and flavonoid content, and antioxidant activities, as measured by ORAC and DPPH assays. Chemical characterization via HPLC-C18-Q-TOF-MS/MS revealed a diverse profile of phenolic and flavonoid compounds, including caffeoylquinic acid derivatives and related transformation products. The neuroprotective potential of the optimized extract was further evaluated through in vitro inhibition assays targeting acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX), alongside a permeability assessment using an in vitro blood–brain barrier (BBB) model. Molecular docking simulations were performed to explore the interactions of apigenin—the most representative flavonoid in the optimal extract—with the three target enzymes. Overall, these findings support the valorization of ABP as a source of bioactive compounds and highlight the potential of PLE as an efficient and sustainable extraction approach. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
30 pages, 4316 KB  
Article
Coumarin– and Dipicolylamine–Terpenoid Hybrids as Selective Carbonic Anhydrases IX and XII Inhibitors: Mechanistic Insights and Selective Anti-Cancer Potential
by Venkatesan Saravanan, Andrea Angeli, Francesco Melfi, Nicola Amodio, Ilenia Valentino, Massimo Gentile, Ilaria D'Agostino, Kathiravan Muthukumaradoss, Gokhan Zengin, Davide Moi, Rahime Simsek, Claudiu T. Supuran and Simone Carradori
Pharmaceuticals 2026, 19(5), 717; https://doi.org/10.3390/ph19050717 - 30 Apr 2026
Abstract
Background: Carbonic Anhydrases (CAs) represent regulators of cell adaptation to hypoxia, pH regulation, and metabolic fitness. Among cancers, multiple myeloma (MM) is a plasma cell malignancy sustained by hypoxia-driven metabolic adaptation, extracellular acidification, and redox imbalance. Tight regulation of tumor extracellular pH, [...] Read more.
Background: Carbonic Anhydrases (CAs) represent regulators of cell adaptation to hypoxia, pH regulation, and metabolic fitness. Among cancers, multiple myeloma (MM) is a plasma cell malignancy sustained by hypoxia-driven metabolic adaptation, extracellular acidification, and redox imbalance. Tight regulation of tumor extracellular pH, mediated by Carbonic Anhydrases IX and XII, is crucial for myeloma survival, progression, and stemness, making these isoforms attractive therapeutic targets. Methods: We designed and synthesized a library of terpenoid-based hybrids by derivatizing chlorothymol and 4-isopropyl-3-methylphenol with either the natural coumarin umbelliferon or the 2,2′-dipicolylamine (DPA) scaffold. This chemical strategy aimed to selectively inhibit tumor-associated CAs IX/XII through coumarin- or DPA-mediated recognition, while terpenoid fragments were introduced to enhance lipophilicity, membrane permeability, and potential redox-modulating properties. The compounds were tested by a Stopped-Flow assay for CA inhibition, in cell-based assays for antiproliferative properties and by means of several antioxidant assays. Results: The most active compounds, connecting the coumarin core to a terpenoid tail, inhibited the targeted CAs in the nanomolar range, showing up higher selectivity over off-target isoforms (I and II). In studies performed on MM cell lines, selected derivatives reduced viability (IC50 = 15.8–85.4 µM) and displayed favorable selectivity over normal cells. In silico investigations suggested that the compounds were able to interact selectively with the target enzymes. Conclusions: Collectively, these results support a dual-targeting strategy in which selective inhibition of tumor-associated CAs, combined with redox modulation, interferes with adaptive mechanisms of MM cells, providing a rational framework for the development of multifunctional agents against metabolically resilient hematological malignancies. Full article
(This article belongs to the Special Issue Enzyme Inhibitors: Potential Therapeutic Approaches, 2nd Edition)
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34 pages, 1444 KB  
Systematic Review
On Molecular Factors in Tympanosclerosis: A Systematic Review with Clinical Implications for Diagnosis and Treatment
by Barbara Parol, Julia Zapart, Grzegorz Ciamciak, Manuela Makiola, Noemi Boguslawska, Alicja Florczak, Zygmunt Domagala and Karolina Dorobisz
Appl. Sci. 2026, 16(9), 4420; https://doi.org/10.3390/app16094420 - 30 Apr 2026
Abstract
Tympanosclerosis is a chronic middle ear disorder characterized by fibrosis, hyalinization, and calcification of the tympanic membrane and ossicles, which often results in conductive hearing loss. The objective of this systematic review was to synthesize current evidence on molecular pathways and genetic susceptibility [...] Read more.
Tympanosclerosis is a chronic middle ear disorder characterized by fibrosis, hyalinization, and calcification of the tympanic membrane and ossicles, which often results in conductive hearing loss. The objective of this systematic review was to synthesize current evidence on molecular pathways and genetic susceptibility factors contributing to the development of this condition. PubMed, Embase, Web of Science, and Google Scholar were searched up to December 2024. Eligible studies were original peer-reviewed articles in English investigating gene expression, genetic polymorphisms, or molecular signaling pathways in human or animal models. Risk of bias was assessed using standardized tools, and results were synthesized narratively due to heterogeneity. Twenty-five studies were included from 1815 screened records. Reported findings implicated inflammatory cytokines, such as TNF-α and IL-6, oxidative stress-related enzymes, including CAT, and iNOS, and bone remodeling pathways involving Wnt signaling, TGF-β1, and osteopontin. Polymorphisms in TLR4, NOS2 and NAT2 were associated with increased susceptibility or severity. Evidence remains limited but highlights potential biomarkers and therapeutic targets. Full article
(This article belongs to the Section Chemical and Molecular Sciences)
19 pages, 3013 KB  
Review
Selective Control Mechanisms, Quantitative Evaluation, and Sustainable Strategies for Cultural Heritage Surface Cleaning
by Jiaxin Zhang, Yutong Liu, Xiang Liu, Shanxiang Xu, Wenxuan Chen and Xinyou Liu
Polymers 2026, 18(9), 1116; https://doi.org/10.3390/polym18091116 - 30 Apr 2026
Abstract
The conservation of cultural heritage artifacts requires precise and controlled cleaning strategies to remove surface contaminants while preserving the structural and aesthetic integrity of the original materials. Over time, artifacts made of stone, paper, textiles, and other materials are exposed to environmental pollution, [...] Read more.
The conservation of cultural heritage artifacts requires precise and controlled cleaning strategies to remove surface contaminants while preserving the structural and aesthetic integrity of the original materials. Over time, artifacts made of stone, paper, textiles, and other materials are exposed to environmental pollution, chemical reactions, and microbial colonization, which lead to the accumulation of complex contaminant layers and progressive material degradation. In recent years, significant advances in materials science have introduced innovative cleaning approaches, including polymer gels, microemulsions, nanomaterials, and enzyme-assisted systems, which enable selective contaminant removal with reduced risk of substrate damage. These methods provide improved control over solvent release, contaminant dissolution, and interaction with sensitive surfaces compared to conventional mechanical and chemical cleaning techniques. In addition, advanced analytical tools such as Raman spectroscopy, surface-enhanced Raman spectroscopy (SERS), and X-ray fluorescence (XRF) have enabled quantitative evaluation of cleaning efficiency and more accurate monitoring of conservation processes. This review summarizes the major contamination mechanisms affecting cultural heritage materials and discusses recent developments in cleaning technologies, functional materials, and evaluation methods. The analysis shows that selective cleaning methods can significantly minimize damage to the underlying substrate, while environmentally friendly functional materials combined with multi-dimensional quantitative evaluation provide an effective and sustainable framework for cultural heritage conservation. Full article
24 pages, 996 KB  
Review
Hepatic Gluconeogenesis and the Antidepressant Effects of Exercise: A Narrative Review
by Hongyu Gong, Jing Miao, Jiheng Yuan, Yuchen Zhu, Huan Xiang, Yangbo Yu, Shi Zhou, Qin Zhang and Yumei Han
Metabolites 2026, 16(5), 310; https://doi.org/10.3390/metabo16050310 - 30 Apr 2026
Abstract
Background: Research indicates that hepatic gluconeogenesis mediates metabolic coupling between the liver and muscles via the Cori cycle and participates in liver–brain axis communication through its metabolic products and regulatory networks, thereby linking it to the pathogenesis of depression. Together, these mechanisms [...] Read more.
Background: Research indicates that hepatic gluconeogenesis mediates metabolic coupling between the liver and muscles via the Cori cycle and participates in liver–brain axis communication through its metabolic products and regulatory networks, thereby linking it to the pathogenesis of depression. Together, these mechanisms form the molecular basis for the antidepressant effects of exercise-regulated hepatic gluconeogenesis. Regular exercise promotes skeletal muscle contraction, causing the muscles to release more lactate into the circulatory system. Lactate acts as a substrate for gluconeogenesis and activates downstream signaling pathways, thereby enhancing the gluconeogenic response. During exercise, glycogenolysis directly provides energy, while lactate produced by glycolysis enters the liver via the Cori cycle to serve as a substrate for gluconeogenesis. By maintaining blood glucose homeostasis, this process ensures a stable energy supply to the brain, thereby improving cognitive and emotional functions. This study aims to elucidate how key substrates, regulatory factors, and rate-limiting enzymes involved in hepatic gluconeogenesis and exercise influence brain energy supply, cognitive function, and emotional regulation during depression. It seeks to identify the potential targets and mechanisms through which exercise exerts its antidepressant effects via hepatic gluconeogenesis, with the goal of providing a theoretical foundation for research into the mechanisms of depression and for clinical exercise interventions. Methods: This review conducted a comprehensive search of the recent literature on exercise, hepatic gluconeogenesis, and depression in major domestic and international databases. Adopting an interdisciplinary approach that integrates hepatic gluconeogenesis and exercise, it synthesizes existing evidence to explore the metabolic mechanisms by which exercise improves depression through the regulation of hepatic gluconeogenesis pathways. Results: Research has found that exercise may modulate hepatic gluconeogenic substrates and regulate the expression of cAMP-responsive element-binding protein in states of depression, regulatory factors such as liver kinase B1, forkhead box protein 01, hepatocyte nuclear factor 4 alpha, and peroxisome proliferator activated receptor gamma co activator factor 1 alpha are used to affect key rate limiting enzymes of hepatic gluconeogenesis, such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, enhance hepatic gluconeogenesis processes, maintain blood glucose homeostasis, ensure brain energy supply, and improve depression. Conclusions: Exercise intervention targeting hepatic gluconeogenesis may be a potential therapeutic strategy for depression. Full article
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