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Search Results (10,603)

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12 pages, 3673 KB  
Communication
Morphometric Characterization of Hemp Achene and Leaf Trichomes Based on X-Ray Micro-CT
by Laura Gargiulo, Sabrina Maria Marsala and Giacomo Mele
Foods 2026, 15(13), 2287; https://doi.org/10.3390/foods15132287 (registering DOI) - 25 Jun 2026
Abstract
Industrial hemp (Cannabis sativa L.) is increasingly being recognized for the production of functional food ingredients and nutraceutical products with broad applications in human nutrition. Its nutrient-rich seeds are of particular interest for their nutritional profile. Moreover, its inflorescences and trichomes provide [...] Read more.
Industrial hemp (Cannabis sativa L.) is increasingly being recognized for the production of functional food ingredients and nutraceutical products with broad applications in human nutrition. Its nutrient-rich seeds are of particular interest for their nutritional profile. Moreover, its inflorescences and trichomes provide sources of nutrient-rich proteins, bioactive compounds, and functional substances for food formulations. Agronomic practices, environmental factors, and genotype considerably influence the hemp nutritional profile; thus, continued interdisciplinary research is needed to standardize quality across supply chains. X-ray micro-computed tomography (micro-CT) combined with 3D image analysis is an emerging non-destructive technique in high-resolution plant phenotyping. The aim of this work was to show the contribution of X-ray micro-CT to the quantitative characterization of the internal hemp seed structure and of the trichomes. The 3D image analysis approach used allowed us to determine many morphometric traits of the different seed parts and of the trichomes. Among them, volume ratios of the different seed parts and the density and morphological characteristics of the trichomes of two cultivars were accurately quantified. Overall, this work showed the contribution of X-ray micro-CT in 3D morphometric characterization of the hemp achene structure and trichomes. The obtained seed morphometric traits could be correlated in future applications with nutritional and/or physiological properties of different hemp varieties in order to support different aspects of the whole hemp supply chain such as the dehulling process, oil and protein recovery, seed quality evaluation, and genotype screening, to which trichome characterization could also contribute. Full article
(This article belongs to the Special Issue Sustainability and Resilience in the Industrial Hemp Supply Chain)
18 pages, 1981 KB  
Article
Mapping the Global Trajectory and Key Trends of Temporal Interference Stimulation
by Li Qi, Zhishun Gao, Xiaomin Pan, Jin Li, Yue Yu, Kai Wang, Qianqian Li and Tongjian Bai
Bioengineering 2026, 13(7), 741; https://doi.org/10.3390/bioengineering13070741 (registering DOI) - 25 Jun 2026
Abstract
Since its inception in 2017, temporal interference stimulation (TIS) has attracted increasing attention as a novel neuromodulation approach with the potential to non-invasively target deep brain structures. As the field moves from initial biophysical validation toward broader experimental and translational applications, a macroscopic [...] Read more.
Since its inception in 2017, temporal interference stimulation (TIS) has attracted increasing attention as a novel neuromodulation approach with the potential to non-invasively target deep brain structures. As the field moves from initial biophysical validation toward broader experimental and translational applications, a macroscopic understanding of its developmental trajectory and thematic evolution is needed. In this study, we systematically mapped the scientific landscape of TIS research using bibliometric methods to characterize its knowledge structure, core themes, and emerging frontiers. The analysis shows that TIS research has expanded rapidly from foundational animal studies and biophysical mechanism validation toward computational head modeling, individualized electric field optimization, and early human applications. Current research is increasingly focused on cross-species scaling, stimulation dosimetry, comparative advantages over other neuromodulation techniques, precise targeting strategies, and potential physiological risks such as high-frequency conduction block. Overall, TIS is evolving from an exploratory biophysical concept into a promising but technically and physiologically complex neuromodulation tool. Overcoming current engineering and translational barriers, particularly through individualized modeling, rigorous optimization, and well-designed human studies, will be essential for establishing TIS as a reliable therapeutic intervention. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
22 pages, 2481 KB  
Review
Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP–SMAD Signaling to Therapeutic Modulation
by Andrea Duminuco, Alessandro Costa, Federica Pilo, Salvatore Scarso, Cesarina Giallongo, Sebastiano Giallongo, Annalisa Santisi, Arianna Sbriglione, Laura Santocono, Giovanni Caocci and Giuseppe A. Palumbo
Biomolecules 2026, 16(7), 947; https://doi.org/10.3390/biom16070947 (registering DOI) - 25 Jun 2026
Abstract
Hepcidin, a 25-amino-acid peptide hormone produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis. By binding the cellular iron exporter ferroportin and inducing its internalization and lysosomal degradation, hepcidin restricts iron entry into plasma from enterocytes, macrophages, and hepatocytes. Its [...] Read more.
Hepcidin, a 25-amino-acid peptide hormone produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis. By binding the cellular iron exporter ferroportin and inducing its internalization and lysosomal degradation, hepcidin restricts iron entry into plasma from enterocytes, macrophages, and hepatocytes. Its transcription is governed by an intricate molecular network that integrates iron status, erythropoietic demand, oxygen tension, and inflammation, with the BMP–HJV–ALK2/SMAD axis acting as the canonical activating pathway and erythroferrone (ERFE) and matriptase-2 (TMPRSS6) as physiological suppressors. Dysregulation of hepcidin underpins a wide spectrum of human diseases: insufficient hepcidin drives hereditary hemochromatosis and the iron overload of congenital and acquired ineffective erythropoiesis diseases and other ineffective erythropoiesis syndromes, whereas excessive or inappropriate hepcidin contributes to anemia of inflammation, anemia of chronic kidney disease, iron-restricted erythropoiesis in cancer, the iron-restrictive anemia of myelofibrosis, and pathogen-restrictive nutritional immunity. Within the myeloproliferative neoplasm spectrum, the divergent hepcidin patterns observed in polycythemia vera (suppressed) and myelofibrosis (inappropriately elevated through dual BMP/ACVR1/SMAD and IL-6/STAT3 hyperactivation) exemplify the clinical relevance of this axis and underpin two opposite pharmacologic strategies. Over the past decade, hepcidin pathway pharmacology has matured from proof-of-concept to regulatory milestones, shifting perspectives on several diseases and markedly improving clinical approaches. Full article
(This article belongs to the Special Issue Iron Metabolism in Cells)
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21 pages, 391 KB  
Article
A Pilot Feasibility Study of Mindful Walking in Older Adults: Exploratory Bayesian Estimates of Psychological Distress and Alexithymia
by Alessandro Germani, Antonella Lopez, Claudia Mirenghi, Manuela Nicoletta Di Masi and Andrea Bosco
Int. J. Environ. Res. Public Health 2026, 23(7), 836; https://doi.org/10.3390/ijerph23070836 (registering DOI) - 25 Jun 2026
Abstract
Population aging demands accessible interventions for psychological well-being in later life. This work evaluated the feasibility and acceptability of an 8-week mindful walking program in community-dwelling older adults and generated exploratory estimates of within-person change across emotional, psychosomatic, and psychological outcomes. Thirteen community-dwelling [...] Read more.
Population aging demands accessible interventions for psychological well-being in later life. This work evaluated the feasibility and acceptability of an 8-week mindful walking program in community-dwelling older adults and generated exploratory estimates of within-person change across emotional, psychosomatic, and psychological outcomes. Thirteen community-dwelling older adults participated in a pilot human trial with assessments at baseline, post-intervention, and one-month follow-up. Measures included depression, anxiety, somatic symptoms, mindfulness, mind wandering, alexithymia, quality of life, and attachment style. Primary feasibility outcomes indicated high acceptability and participant satisfaction, good physiological tolerance and full adherence. Secondary exploratory analyses suggested within-person reductions in depressive symptoms and alexithymia, while somatic symptoms decreased notably by follow-up. Mindfulness increased and was maintained over time, while mind wandering displayed a probable long-term decrease. Psychological quality of life improved and remained elevated, whereas physical, social, and environmental quality-of-life domains showed uncertain trends. Trait anxiety decreased post-intervention but returned toward baseline at follow-up, while state anxiety and attachment styles remained stable. Within pilot design limits, mindful walking may be a feasible intervention for older adults, associated with exploratory within-person patterns suggesting possible improvements in certain psychological outcomes, which should be interpreted as preliminary and descriptive signals pending confirmation in controlled trials. These preliminary findings support further investigation in controlled trials to determine effectiveness and to formally test hypothesized mechanisms. Full article
(This article belongs to the Topic Healthy, Safe and Active Aging, 3rd Edition)
23 pages, 49897 KB  
Article
Psychophysiological Recovery Discordance and Residual Cardiovascular Risk in Cold-Region Community Outdoor Spaces
by Jun Zhao, Tianheng Zhang, Yao Fu, Xi Wang, Chao Yang and Yutong Zhang
Buildings 2026, 16(13), 2520; https://doi.org/10.3390/buildings16132520 (registering DOI) - 25 Jun 2026
Abstract
Cold-region community outdoor spaces are not only everyday activity settings for older adults in winter, but also public-space types that need to be translated into design evidence for architecture and healthy human-settlement research. Existing restorative-environment studies usually treat improved mood, perceived restoration, and [...] Read more.
Cold-region community outdoor spaces are not only everyday activity settings for older adults in winter, but also public-space types that need to be translated into design evidence for architecture and healthy human-settlement research. Existing restorative-environment studies usually treat improved mood, perceived restoration, and environmental appraisal as evidence of health benefits. The key finding of this study is that subjective restoration and physiological recovery are not always synchronized after outdoor exposure in cold-region communities. This discordance reveals a design risk and an innovative value that can be overlooked when restoration is evaluated only through perception-based indicators. Based on a winter field exposure experiment with 345 older adults in a community in Shenyang, China, this study compared staged changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), POMS, ROS, and ENPQ across an activity plaza, a greenway walkway, and a street corridor. It further developed a psychophysiological concordance classification and a residual cardiovascular risk indicator for the recovery period. The greenway walkway showed the most stable concordant recovery, with 86.84% of women and 79.35% of men showing concordant recovery. The activity plaza showed a clear pattern of emotional recovery: the proportions of women and men whose psychological state improved without a synchronized SBP decrease were 61.58% and 50.32%, respectively. The street corridor had the highest recovery-failure rates, at 92.63% for women and 91.61% for men. Among women, 90.53% reached SBP values of 140 mmHg or higher during the walking phase in the street corridor, and 59.47% remained above this risk threshold during recovery. These results show that health evaluation of cold-region community outdoor spaces should not rely only on subjective restoration indicators, but should also include psychophysiological concordance and residual risk after exposure. The study translates site health effects into three architectural design judgments: concordant-restoration spaces, emotional-restoration spaces, and recovery-failure spaces, providing a testable evidence framework for age-friendly community renewal, path organization, green buffering, and winter wind-protection design. Full article
(This article belongs to the Special Issue Healthy Aging and Built Environment)
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14 pages, 1858 KB  
Article
Selenium-Biofortified Strawberries Improve Glucose Homeostasis and Hepatic Function: A 30-Day Randomized Controlled Trial in Healthy Adults
by Sonya Vasto, Luigi Di Rosa, Vincenzo Ferrantelli, Antonino Salvatore Fiore, Carola Pia Giordano, Alessia Cannizzaro, Leo Sabatino, Andrea Macaluso, Rosalia Caldarella, Gaetano Felice Caldara and Sara Baldassano
Nutrients 2026, 18(13), 2078; https://doi.org/10.3390/nu18132078 (registering DOI) - 25 Jun 2026
Abstract
Background: Selenium is an essential trace element for humans that plays a key role in glucose homeostasis and hepatic function. Biofortification is a sustainable agricultural technique able to increase micronutrients and reduce pesticides in crops. Purpose: The present study aimed to [...] Read more.
Background: Selenium is an essential trace element for humans that plays a key role in glucose homeostasis and hepatic function. Biofortification is a sustainable agricultural technique able to increase micronutrients and reduce pesticides in crops. Purpose: The present study aimed to examine whether the consumption of strawberries biofortified with selenium in a healthy population for 30 days would increase the endogenous selenium concentration, and whether and to what extent it would impact glucose homeostasis and hepatic function. Methods: Thirty-five healthy participants, male and female, were divided by double-blinding into three different groups that received control strawberries (100 g/day), selenium-biofortified strawberries (100 g/day) or selenium in tablets (100 µg/day) for 30 consecutive days. Blood samples were collected at the beginning (T0, baseline) and at the end of the nutritional intervention (T1), and the groups were compared for differences in serum selenium concentrations, glucose homeostasis aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and albumin (ALB). Results: Biofortification increased the selenium concentration in strawberries by 419%. Supplementation with biofortified strawberries increased serum selenium levels by about 73.6%, while standard selenium supplementation showed no statistically significant effect. Selenium-biofortifies strawberries reduced fasting glucose and insulin, and improved insulin sensitivity and β cell function. They also reduced AST and GGT within the physiological range. Conclusions: These data suggest that supplementation for 30 days with selenium-biofortified strawberries is safe and is associated with favourable changes in markers of glucose regulation. Selenium supplementation, at the standard market dose of 100 µg/day, demonstrated no significant clinical differences during the studied period. Full article
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23 pages, 1773 KB  
Review
Melatonin and Mitochondrial Redox Homeostasis in Reproduction: Mechanistic Links Between Circadian Signaling and Fertility Outcomes
by Sofoklis Stavros, Panagiotis Christopoulos, Stefanos Dafopoulos, Chrysi Christodoulaki, Efthalia Moustakli, Anastasios Potiris, Maria Tzeli, Athanasios Zikopoulos, Konstantinos Dafopoulos and Peter Drakakis
Biology 2026, 15(13), 1000; https://doi.org/10.3390/biology15131000 (registering DOI) - 25 Jun 2026
Abstract
The pineal gland regulates circadian physiology through the periodic production of melatonin (MLT). In addition to its established role as a chronobiotic agent, MLT regulates redox homeostasis and mitochondrial physiology. Mitochondria and redox-active molecules, particularly reactive oxygen species (ROS), play essential roles in [...] Read more.
The pineal gland regulates circadian physiology through the periodic production of melatonin (MLT). In addition to its established role as a chronobiotic agent, MLT regulates redox homeostasis and mitochondrial physiology. Mitochondria and redox-active molecules, particularly reactive oxygen species (ROS), play essential roles in reproduction, including gamete physiology, fertilization, and early embryonic development. Although excessive oxidative stress (OS) impairs fertility, controlled ROS signaling is necessary for normal reproductive function. This comprehensive review synthesizes current evidence regarding MLT as a key intermediary linking circadian signaling with mitochondrial physiology and redox homeostasis. We discuss molecular pathways through which MLT regulates mitochondrial function, including activation of the Nrf2 signaling pathway, modulation of mitochondrial permeability transition, regulation of electron transport chain (ETC) efficiency, and apoptotic signaling. Furthermore, this study investigates MLT’s ability to scavenge free radicals and activate antioxidant defense mechanisms. Moreover, we review novel findings regarding the effects of MLT in experimental animals and humans, assisted reproductive technologies (ART) such as in vitro fertilization (IVF), and consider the translational significance of the hormone as an enhancer of fertility. We also highlight gaps in the literature, including methodological inconsistencies, supraphysiologic doses, and insufficient data from large human cohorts. Lastly, we discuss an integrative model whereby MLT may function as an important regulator of mitochondrial redox balance, with potential implications for reproductive physiology and reproductive outcomes, and propose new avenues for investigation. Full article
(This article belongs to the Section Developmental and Reproductive Biology)
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16 pages, 3094 KB  
Article
Not All Microbiomes Reflect Chronic Pain: Evidence from the Urinary Tract in a Case–Control Study
by Lisa Goudman and Maarten Moens
J. Clin. Med. 2026, 15(13), 4931; https://doi.org/10.3390/jcm15134931 (registering DOI) - 25 Jun 2026
Abstract
Background/Objectives: Chronic pain is increasingly conceptualized as a systemic condition characterized by central sensitization, autonomic dysregulation, and persistent neuroimmune and neuroendocrine alterations. These systemic changes have been linked to microbial dysbiosis, most prominently within the gut microbiome. In contrast, the relevance of [...] Read more.
Background/Objectives: Chronic pain is increasingly conceptualized as a systemic condition characterized by central sensitization, autonomic dysregulation, and persistent neuroimmune and neuroendocrine alterations. These systemic changes have been linked to microbial dysbiosis, most prominently within the gut microbiome. In contrast, the relevance of the urinary microbiome outside primary urological disease remains poorly understood, particularly in non-urological chronic pain conditions. The objective of this study was to determine whether patients with chronic low back pain exhibit differences in urinary microbial diversity, community composition, or taxon-specific abundance compared with pain-free controls. Methods: In this age- and sex-matched case–control study, midstream urine samples were collected from ten patients with chronic low back pain and ten pain-free controls and analyzed using 16S rRNA gene sequencing (V4 region). Sequence data were processed using nf-core/ampliseq and DADA2. Alpha diversity, beta diversity, and differential abundance were assessed using depth-adjusted models, compositional and phylogenetically informed distance metrics, and ANCOM-BC2, with multiple sensitivity analyses to account for the low-biomass nature of urinary microbiome data. Results: After accounting for sequencing depth, no significant differences in alpha diversity were observed between patients and controls for any metric. Beta diversity analyses revealed no significant differences in overall community composition between groups across all distance measures, and dispersion was comparable between groups. Differential abundance analysis did not identify any bacterial taxa that differed significantly between patients and controls after correction for multiple testing. Conclusions: In this cohort, chronic low back pain was not associated with detectable alterations in the urinary microbiome. These findings suggest that, unlike the gut microbiome, urinary microbial communities may be relatively stable in the context of non-urological chronic pain, highlighting the importance of phenotype specificity and multidimensional approaches in microbiome-based pain research. Full article
(This article belongs to the Section Anesthesiology)
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12 pages, 788 KB  
Communication
Cytokine Profiles in Patients with Type 2 Diabetes Across Different Durations of the Disease: An Exploratory Cross-Sectional Study
by Bernard Kordas, Jan Banach and Judyta K. Juranek
Curr. Issues Mol. Biol. 2026, 48(7), 651; https://doi.org/10.3390/cimb48070651 (registering DOI) - 25 Jun 2026
Abstract
Type 2 diabetes (T2D) is often accompanied by chronic low-grade inflammation, with altered cytokine balance. Although cytokine profiles have often been compared between patients with T2D and healthy individuals, less is known about how they differ among patients with varying disease duration. The [...] Read more.
Type 2 diabetes (T2D) is often accompanied by chronic low-grade inflammation, with altered cytokine balance. Although cytokine profiles have often been compared between patients with T2D and healthy individuals, less is known about how they differ among patients with varying disease duration. The aim of this exploratory study was to compare selected pro-inflammatory and anti-inflammatory cytokines in patients with shorter and longer duration of clinically diagnosed T2D. Anonymized surplus serum samples from 18 patients with T2D were analyzed. Patients were divided into two groups according to disease duration: 1–7 years and 8–16 years post-T2D diagnosis. Serum concentrations of six pro-inflammatory cytokines (IL-1β, IL-5, IL-6, IL-8, TNF-α and IFN-γ), three cytokines with anti-inflammatory or immunoregulatory functions (IL-2, IL-4, IL-10), and pro- and anti-inflammatory ratios were measured. All tests were performed using MAGLUMI X8 (Snibe Diagnostics, Shenzhen, China) high-sensitivity chemiluminescent immunoassay according to the manufacturer’s guidelines. Statistical analysis of the data obtained was performed using GraphPad Prism (Boston, MA, USA). The longer-duration T2D group showed higher median concentrations of several pro-inflammatory cytokines, particularly IL-6, IL-8, TNF-α, and IFN-γ, compared with the shorter-duration group. Several values in the longer-duration group exceeded the assay-specific reference intervals provided by the diagnostic platform. Anti-inflammatory and immunoregulatory cytokines showed less consistent differences between groups. Correlation analysis indicated stronger correlations among pro-inflammatory cytokines than among anti-inflammatory or immunoregulatory cytokines. This cross-sectional study suggests that cytokine profiles may differ between patients with shorter and longer durations of T2D, with a pattern consistent with a more pro-inflammatory profile in the longer-duration group. Because of the small sample size, absence of healthy controls, and limited availability of clinical covariates, these findings should be interpreted as descriptive rather than confirmatory and require validation in larger, longitudinal studies with detailed metabolic characterization. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Disease)
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27 pages, 953 KB  
Review
Detecting and Improving Human Cognitive State in Real-Time Using Data-Driven Adaptive Systems: A Systematic Review
by Abhineet Rajendra Kulkarni and Pranav Madhav Kuber
Bioengineering 2026, 13(7), 734; https://doi.org/10.3390/bioengineering13070734 (registering DOI) - 24 Jun 2026
Abstract
Changes in human attention, workload, or alertness over time can affect task performance and may even increase the risk of injury. Detecting these changes in real time can be beneficial in improving system performance and safety. We reviewed 27 studies that developed models [...] Read more.
Changes in human attention, workload, or alertness over time can affect task performance and may even increase the risk of injury. Detecting these changes in real time can be beneficial in improving system performance and safety. We reviewed 27 studies that developed models to sense physiological signals, classify one’s cognitive state, and deliver automated intervention. Interventions included providing real-time feedback, adjusting the task’s difficulty, or modifying automation levels across driving, education, rehabilitation, and human–robot collaboration applications. The findings showed that electroencephalography (EEG) sensors were used in 70% of studies, with attention (56%) and mental workload (26%) considered as the most targeted cognitive states. Within-subject classification reached 81.85–95.81% for multi-class tasks in laboratory settings. The most common interventions included neurofeedback display (30%) and task difficulty adjustment (19%), while automation adjustment was less frequent (11%). Only 33% of studies mentioned a latency of 15 milliseconds to 2.5 s, and all systems operated reactively by detecting cognitive states after their onset rather than anticipating them. The provided recommendations focus on the detection of multiple interacting cognitive states and predictive cognitive state trajectories. This review presents key directions for future research and provides a foundation for designing more effective cognitive state adaptive systems. Full article
12 pages, 2953 KB  
Article
High-Performance Integrated Self-Powered PNP Hydrogel Sensor for Wearable Human Monitoring
by Jiawei Long, Pan Niu, Hongbing Li and Yong Zhang
Polymers 2026, 18(13), 1572; https://doi.org/10.3390/polym18131572 (registering DOI) - 24 Jun 2026
Abstract
With the rapid advancement of wearable technologies, high-performance flexible sensors have garnered significant research interest. This study presents a PAM-5 hydrogel characterized by exceptional tensile strain (425%), superior compressive modulus (325 kPa), and notable ionic conductivity (1.1 S/m), serving as a robust mechanical [...] Read more.
With the rapid advancement of wearable technologies, high-performance flexible sensors have garnered significant research interest. This study presents a PAM-5 hydrogel characterized by exceptional tensile strain (425%), superior compressive modulus (325 kPa), and notable ionic conductivity (1.1 S/m), serving as a robust mechanical framework and electrical foundation for developing advanced sensors. The PNP-5 integrated hydrogel sensor fabricated from this material demonstrates an extensive sensing range (2–53 kPa), remarkable sensitivity, and rapid response time (~321 ms), with its outstanding performance attributed to the synergistic structural design. Furthermore, the sensor exhibits excellent durability, maintaining consistent voltage output (~6.5 mV) across 1000 compression cycles, confirming its long-term operational stability. Through real-time monitoring of physiological signals and biomechanical movements including finger bending, respiration, and grasping, combined with spatial pressure mapping experiments using a 5 × 5 array touchpad, the device’s potential applications in wearable sensing platforms and human–machine interface systems are effectively demonstrated. This self-powered hydrogel sensor not only advances the performance metrics of flexible electronic devices but also establishes a solid experimental basis for future development of intelligent materials in health monitoring and interactive technologies. Full article
(This article belongs to the Special Issue Application and Development of Polymer Hydrogel)
21 pages, 5583 KB  
Review
Nutrition as the Intelligent Nexus: Integrating Precision Farming into Sustainable Ruminant Systems
by Luis O. Tedeschi, Egleu D. M. Mendes and Marcia H. M. R. Fernandes
Agriculture 2026, 16(13), 1379; https://doi.org/10.3390/agriculture16131379 (registering DOI) - 24 Jun 2026
Abstract
Global agriculture faces a dual imperative: increase food production to meet rising demand while simultaneously reducing environmental impacts and resource inefficiencies. Addressing this challenge requires repositioning ruminant nutrition as the intelligent nexus linking crop and livestock production within Integrated Crop–Livestock Systems (ICLS). In [...] Read more.
Global agriculture faces a dual imperative: increase food production to meet rising demand while simultaneously reducing environmental impacts and resource inefficiencies. Addressing this challenge requires repositioning ruminant nutrition as the intelligent nexus linking crop and livestock production within Integrated Crop–Livestock Systems (ICLS). In this role, nutrition becomes central to restoring ecological, nutritional, and economic synergies that have been fragmented by decades of agricultural specialization. While ICLS provides the ecological foundation, Precision Livestock Farming delivers the technological and analytical infrastructure necessary to operationalize integration at the individual-animal level. Real-time sensing, Internet of Things platforms, and Artificial Intelligence (AI) enable dynamic monitoring of animal physiology, behavior, and environmental interactions across scales. A key advancement in this evolution is the development of Hybrid Intelligent Mechanistic Models (HIMM), which integrate biologically grounded mechanistic models with data-driven AI approaches. By combining interpretability with adaptive learning, HIMM enhances predictive accuracy, extrapolative capacity, and decision transparency, enabling the creation of digital twins that simulate biological responses before management interventions are implemented. Such architectures extend precision nutrition beyond feed efficiency and methane mitigation to include nutrient density and product quality, thereby linking different ecosystem processes directly to human dietary needs. Integrating nutrition with advanced modeling and monitoring tools can help livestock systems move beyond static “net-zero” benchmarks toward sustainable strategies that are responsive to local production contexts. In this reframed paradigm, nutrition is not merely a production input but the central analytical framework that computationally links biological mechanisms, environmental stewardship, technological innovation, and human health within sustainable ruminant systems. Full article
(This article belongs to the Section Farm Animal Production)
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15 pages, 1228 KB  
Review
Hepassocin (FGL-1) as a Hepatokine in Liver Physiology and Metabolic Dysfunction: A Narrative Review
by Hung-Chih Chen, Hiong-Ping Hii, Kai-Pi Cheng, Hung-Tsung Wu, Hsin-Yu Kuo and Horng-Yih Ou
Int. J. Mol. Sci. 2026, 27(13), 5699; https://doi.org/10.3390/ijms27135699 (registering DOI) - 24 Jun 2026
Abstract
Hepassocin, also known as fibrinogen-like protein 1 (FGL-1), is a liver-derived secretory protein initially identified as a mitogenic factor involved in hepatocyte proliferation and liver regeneration. Increasing evidence has subsequently suggested that FGL-1 functions as a hepatokine linking hepatic metabolic stress to systemic [...] Read more.
Hepassocin, also known as fibrinogen-like protein 1 (FGL-1), is a liver-derived secretory protein initially identified as a mitogenic factor involved in hepatocyte proliferation and liver regeneration. Increasing evidence has subsequently suggested that FGL-1 functions as a hepatokine linking hepatic metabolic stress to systemic metabolic regulation. Experimental and clinical studies have demonstrated that circulating FGL-1 levels are associated with obesity, insulin resistance, metabolic dysfunction-associated steatotic liver disease (MASLD), and type 2 diabetes mellitus (T2DM). Mechanistically, FGL-1 appears to contribute to metabolic dysfunction by impairing insulin signaling and promoting hepatic lipid accumulation, although its precise molecular targets remain incompletely defined. In addition to its metabolic roles, FGL-1 has been identified as a major ligand of lymphocyte activation gene-3 (LAG-3), implicating it in immune modulation and tumor progression, particularly in hepatocellular carcinoma (HCC). However, most available human data are observational, and conflicting findings from experimental models suggest that FGL-1 may function as a context-dependent mediator rather than a purely pathogenic factor. Given the expanding but sometimes conflicting evidence, a comprehensive understanding of FGL-1 biology may provide important insights into the complex interactions among hepatic stress responses, metabolic dysfunction, and immune regulation. This review therefore examines the current evidence regarding the physiological and pathological roles of FGL-1 and highlights key unresolved questions that may influence future translational research and therapeutic development. Full article
(This article belongs to the Special Issue Molecular Insights into Chronic Liver Disease and Liver Failure)
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13 pages, 1365 KB  
Review
Regenerative Inflammation in IBD: How Type I Interferons and TNF Cross-Talk Converts Epithelial Repair into Therapeutic Response
by Emelia A. M. Hinton, Roslyn A. Kemp, Michael Schultz and Safina Gadeock
Cells 2026, 15(13), 1144; https://doi.org/10.3390/cells15131144 (registering DOI) - 24 Jun 2026
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Abstract
Inflammatory bowel diseases (IBD) are increasingly recognized as disorders in which epithelial dysfunction and maladaptive regeneration may be as important as immune dysregulation. Tumor necrosis factor (TNF), a key mediator of intestinal inflammation and a therapeutic target, plays a dual role in both [...] Read more.
Inflammatory bowel diseases (IBD) are increasingly recognized as disorders in which epithelial dysfunction and maladaptive regeneration may be as important as immune dysregulation. Tumor necrosis factor (TNF), a key mediator of intestinal inflammation and a therapeutic target, plays a dual role in both immune activation and epithelial repair by regulating progenitor cell expansion, lineage plasticity, and chemokine signaling in the intestinal epithelium. During acute injury, TNF-associated responses are generally considered adaptive, supporting crypt repair, barrier restitution, and secretory remodeling pathways. However, in chronic disease, persistent TNF exposure, potentially reinforced by type I interferons (IFN-I), may contribute to the persistence of epithelial regenerative pathways. IFN-I signaling has been suggested in experimental and translational studies to reinforce chemokine networks and transcriptional imprinting. We propose that this potentially converts physiological repair into a sustained state of what we have termed “regenerative inflammation,” in which epithelial-derived signals may perpetuate immune recruitment and tissue remodeling. Such TNF-IFN-imprinted epithelial states may contribute to sustained pathology in a subset of patients and could be associated with reduced responsiveness to anti-TNF therapy, although direct causal evidence in human disease remains limited. By integrating mechanistic, organoid-based, and clinical observational evidence, we propose that chronic TNF–IFN crosstalk may contribute to a self-sustaining regenerative inflammatory circuit, providing a conceptual framework for disease persistence in IBD and highlighting potential opportunities to target epithelial-immune interactions. Full article
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21 pages, 2781 KB  
Review
Ex Vivo Liver Perfusion as a Platform for Gene Therapy, Immunotherapy, Pharmacology, and Personalized Medicine
by Paul Travers, Yichen Wang, Yan Yan, Jiang Zou, Nabanita Halder, Kristin E. Clift, Xiaojun Cai, Robert L. Kruse, Vivek Kumbhari, Baoan Ji, Liu Yang and Yuting Huang
Livers 2026, 6(4), 55; https://doi.org/10.3390/livers6040055 (registering DOI) - 24 Jun 2026
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Abstract
Ex vivo liver perfusion (EVLP) sustains human or large animal livers outside the body under near-physiological conditions, enabling functional monitoring for lactate clearance, bile production, and oxygen consumption and allowing targeted therapeutic interventions. Originally developed to optimize donor grafts for transplantation, EVLP has [...] Read more.
Ex vivo liver perfusion (EVLP) sustains human or large animal livers outside the body under near-physiological conditions, enabling functional monitoring for lactate clearance, bile production, and oxygen consumption and allowing targeted therapeutic interventions. Originally developed to optimize donor grafts for transplantation, EVLP has evolved into a powerful translational research platform bridging preclinical discovery and early clinical translation. This review discusses EVLP as a platform for gene therapy, immunotherapy, pharmacology, and personalized medicine, with particular emphasis on gene- and immune-based interventions as mechanistically mature exemplars. We consolidate advances in pharmacological testing and toxicity modeling, viral and non-viral gene delivery, genome engineering, and immunomodulation using perfused livers. We further describe emerging applications, including autologous EVLP pathways for organ-confined therapy, ex vivo liver surgery, and bioengineering strategies such as biliary organoid repair, RNA interference, and mitochondrial transfer. We highlight how these applications align with a paradigm shift in biomedical research, including the NIH’s recent initiative to prioritize human-based experimental models over animal-only studies. By leveraging transplant-declined or surgically resected organs that would otherwise be unused, ex vivo perfusion bridges the gap between pre-clinical testing and clinical practice, enabling real-time evaluation of interventions in functional human tissue. We discuss both the scientific opportunities afforded by EVLP and the technical, biosafety, and ethical challenges that must be addressed to enable responsible clinical translation. Full article
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