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17 pages, 3404 KB  
Article
Photoresponsive Ru Complex–Gold Nanoparticle Hybrids for Theranostics: A Theoretical Study of Electronic Structure and Luminescence-Based Detection
by Niq Catevas and Athanassios Tsipis
Molecules 2025, 30(22), 4432; https://doi.org/10.3390/molecules30224432 (registering DOI) - 16 Nov 2025
Abstract
Photoactivatable nitric oxide donors (photoNORMs) are promising agents for controlled NO release and real-time optical tracking in biomedical theranostics. Here, we report a comprehensive density functional theory (DFT) and time-dependent DFT (TDDFT) study on a series of hybrid ruthenium–gold nanocluster systems of the [...] Read more.
Photoactivatable nitric oxide donors (photoNORMs) are promising agents for controlled NO release and real-time optical tracking in biomedical theranostics. Here, we report a comprehensive density functional theory (DFT) and time-dependent DFT (TDDFT) study on a series of hybrid ruthenium–gold nanocluster systems of the general formula [(L)Ru(NO)(SH)@Au20], where L = salen, bpb, porphyrin, or phthalocyanine. Structural and bonding analyses reveal that the Ru–NO bond maintains a formal {RuNO}6 configuration with pronounced Ru → π*(NO) backbonding, leading to partial reduction of the NO ligand and an elongated N–O bond. Natural Bond Orbital (NBO), Natural Energy Decomposition Analysis (NEDA), and Extended Transition State–Natural Orbitals for Chemical Valence (ETS–NOCV) analyses confirm that Ru–NO bonding is dominated by charge-transfer and polarization components, while Ru–S and Au–S linkages exhibit a delocalized, donor–acceptor character coupling the molecular chromophore with the metallic cluster. TDDFT results reproduce visible–near-infrared (NIR) absorption features arising from mixed metal-to-ligand and cluster-mediated charge-transfer transitions. The calculated zero–zero transition and reorganization energies predict NIR-II emission (1.8–3.8 μm), a region of high biomedical transparency, making these systems ideal candidates for luminescence-based NO sensing and therapy. This study establishes fundamental design principles for next-generation Ru-based photoNORMs integrated with plasmonic gold nanoclusters, highlighting their potential as multifunctional, optically trackable theranostic platforms. Full article
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15 pages, 706 KB  
Article
A Study on the Acceptance of Smart Cane Technology Among Chinese Older Adults
by Yibing Chen, Yi An, Zihao Chen, Dingbang Luh and Tiansheng Xia
Healthcare 2025, 13(22), 2934; https://doi.org/10.3390/healthcare13222934 (registering DOI) - 16 Nov 2025
Abstract
Background: Although smart products improve older adults’ quality of life, their acceptance and usage of smart assistive devices remain relatively low, and the influencing factors remain unclear. Methods: This study takes canes, which are commonly used by older adults, as the research [...] Read more.
Background: Although smart products improve older adults’ quality of life, their acceptance and usage of smart assistive devices remain relatively low, and the influencing factors remain unclear. Methods: This study takes canes, which are commonly used by older adults, as the research object. To explore older adults’ acceptance of smart canes and the influencing factors, we constructed an integrated framework based on the extended Technology Acceptance Model (TAM), which incorporates multiple variables: Perceived Usefulness (PU), Perceived Ease of Use (PEOU), Attitude (ATT), Social Influence (SI), Safety Trust (ST), Self-Efficacy (SE), and Behavioral Intention (BI). A questionnaire survey was conducted to collect 232 valid responses, and structural equation modeling (SEM) was employed for data analysis. Results: The results indicate that factors including PU, PEOU, and SI have significant impacts on older adults’ ATT towards using smart canes, their SE, and BI. Among these factors, ATT and SE play a mediating role between PU, PEOU, SI, and BI in using smart canes. Conclusions: The practical implications of the current results are discussed with the aim of providing empirical evidence for the development and application of smart assistive devices for older adults. Full article
(This article belongs to the Special Issue Emerging Technologies for Person-Centred Healthcare)
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24 pages, 1989 KB  
Article
A Novel Mechanism Underlying Resistance to Soybean Cyst Nematode in the Resistant Soybean HN531
by Jia You, Runnan Zhou, Ying Yu, Sobhi F. Lamlom, Yanfeng Hu, Jinrong Li, Han Li and Jiajun Wang
Agronomy 2025, 15(11), 2630; https://doi.org/10.3390/agronomy15112630 (registering DOI) - 16 Nov 2025
Abstract
The soybean cyst nematode (Heterodera glycines, SCN) is the leading pathogen causing economic losses in soybean production worldwide. Using resistant cultivars is the most sustainable control method, yet the molecular basis of this resistance remains unclear. Heinong 531 (HN531), a high-yield [...] Read more.
The soybean cyst nematode (Heterodera glycines, SCN) is the leading pathogen causing economic losses in soybean production worldwide. Using resistant cultivars is the most sustainable control method, yet the molecular basis of this resistance remains unclear. Heinong 531 (HN531), a high-yield soybean variety rich in seed oil, shows broad resistance to multiple SCN races. In this research, we studied HN531’s resistance to SCN races 3 and 5 through phenotypic assessment and comparative transcriptomics. Although initial infection rates were similar between resistant HN531 and the susceptible Dongsheng 1 (DS1), HN531 limited later nematode development inside roots, with fewer progressing to the J2 stage and maturing females. RNA-seq at 5 days post-infection revealed 1459 differentially expressed genes (DEGs) in HN531, mainly involved in secondary metabolite pathways, especially phenylpropanoid biosynthesis. We pinpointed a β-glucosidase gene (Glyma.12G053800, BGLU) upregulated after SCN infection and naturally more expressed in HN531 roots than DS1. Functional tests using Agrobacterium rhizogenes-mediated hairy root transformation showed that overexpressing Glyma.12G053800 in the susceptible DS1 significantly decreased SCN development and adult female counts by around 65%, without affecting initial infection. These findings suggest Glyma.12G053800 contributes to SCN resistance via phenylpropanoid-driven secondary metabolism, offering new insights into nematode resistance pathways and a valuable genetic resource for breeding broad-spectrum resistant soybean varieties. Full article
(This article belongs to the Section Agricultural Biosystem and Biological Engineering)
21 pages, 3799 KB  
Article
Public Acceptance Mechanisms of Han Dynasty Cultural Symbols in Landscape Design: An Empirical Study Based on the Cognition–Attitude–Behavior Model
by Weidi Zhang and Xinyue Cai
Heritage 2025, 8(11), 481; https://doi.org/10.3390/heritage8110481 (registering DOI) - 16 Nov 2025
Abstract
As traditional culture finds increasingly widespread application in visual communication and public landscapes, the public’s acceptance mechanisms for cultural symbols have emerged as a critical issue affecting cultural sustainability. In the context of globalization and digitalization, balancing cultural authenticity with dissemination efficiency has [...] Read more.
As traditional culture finds increasingly widespread application in visual communication and public landscapes, the public’s acceptance mechanisms for cultural symbols have emerged as a critical issue affecting cultural sustainability. In the context of globalization and digitalization, balancing cultural authenticity with dissemination efficiency has become a core issue in driving cultural innovation and sustainable utilization. Grounded in the Cognition–Attitude–Behavior model, this study examines how cognition, attitude, and behavior interact in shaping public responses to Han Dynasty cultural symbols in contemporary landscape design. The research adopts a three-stage framework—comprising theoretical construction, data collection, and analytical validation—and uses the Han Yangling National Archaeological Site Park as a representative Han cultural context. A total of 172 valid questionnaires were analyzed to reveal the cognitive and emotional mechanisms through which the public engages with Han cultural symbols in modern landscapes. Results indicate that cognition not only exerts a direct positive influence on behavioral intention but also plays a significant mediating role through affective attitudes, validating the pivotal mediating function of attitudes in the cultural symbol acceptance process. These findings provide empirical evidence and practical strategies for the contemporary dissemination of traditional cultural symbols and the sustainable utilization of cultural heritage. Full article
(This article belongs to the Section Cultural Heritage)
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18 pages, 1058 KB  
Article
IL-34 as a Novel Mediator Linking Vitamin D Deficiency with Osteoporosis and Knee Osteoarthritis
by Nader Tarabeih, Ali Sleiman, Alexander Kalinkovich, Shai Ashkenazi, Adel Shalata and Gregory Livshits
Int. J. Mol. Sci. 2025, 26(22), 11090; https://doi.org/10.3390/ijms262211090 (registering DOI) - 16 Nov 2025
Abstract
Vitamin D deficiency (VDD) is a widespread human condition closely associated with musculoskeletal disorders, involving alterations in body composition and systemic inflammation. In this cross-sectional study, 1075 adults were classified into a VDD (n = 304) group and a VD sufficient (VDS) group [...] Read more.
Vitamin D deficiency (VDD) is a widespread human condition closely associated with musculoskeletal disorders, involving alterations in body composition and systemic inflammation. In this cross-sectional study, 1075 adults were classified into a VDD (n = 304) group and a VD sufficient (VDS) group (n = 771). Body composition measurements, including the fat mass-to-weight ratio (FM/WT), were assessed using bioelectrical impedance analysis. Plasma levels of IL-9, IL-34, and MCP-1 were also measured. Data on osteoporosis (OP) and knee osteoarthritis (KOA) were collected. Regression analyses indicated that FM/WT was independently associated with VDD, which in turn was linked to elevated IL-34 levels. Individuals with VDD had a significantly higher prevalence of OP and KOA compared with those with VDS. Structural equation modeling confirmed and quantified these associations, suggesting that FM/WT is a significant predictor of VDD status (β = 0.305, 95% CI: 0.231–0.367). VDD is directly associated with elevated IL-34 levels (β = 0.353, 95% CI: 0.308–0.398), while IL-34 levels, in turn, are a possible cause of KOA (β = 0.573, 95% CI: 0.460–0.687) and OP (β = 0.433, 95% CI: 0.329–0.536). Our data clearly demonstrate existence of a physiological-pathological continuum: obesity-VDD-IL-34 and both OP and KOA. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases, 5th Edition)
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22 pages, 2347 KB  
Article
Nitrogen and Water Regulate the Soil Microbial Carbon Cycle in Wheat Fields Primarily via the Pentose Phosphate Pathway
by Qingmin Ma, Bisheng Wang, Quanxiao Fang, Zhongqing Zhao, Yusha Cui and Xiaolu Sun
Agronomy 2025, 15(11), 2629; https://doi.org/10.3390/agronomy15112629 (registering DOI) - 16 Nov 2025
Abstract
To clarify how nitrogen (N) and water regulate the microbe mediated carbon (C) cycle in farmland, a 3-year experiment was conducted in a wheat–maize rotation at Jiaozhou Station, North China. Twelve treatments combined four drip irrigation regimes (T1: no irrigation; T2: 40 mm [...] Read more.
To clarify how nitrogen (N) and water regulate the microbe mediated carbon (C) cycle in farmland, a 3-year experiment was conducted in a wheat–maize rotation at Jiaozhou Station, North China. Twelve treatments combined four drip irrigation regimes (T1: no irrigation; T2: 40 mm irrigation at flowering; T3: 40 mm irrigation at the grain filling stage; T4: both, 40 mm each) and three N levels (N0: 0 kgN·hm−2; N1: 92 kgN·hm−2; N2: 184 kgN·hm−2). In this study, we measured wheat yield and biomass, soil organic carbon and nitrogen content, soil respiration, soil microbial community, and C-metabolic genes. The results showed that wheat yield increased with N, peaking at 8949.81 kg·hm−2 in the N2T3 treatment, while irrigation had no significant independent effect on yield but interacted with nitrogen fertilization: under identical nitrogen levels (N1, N2), yields in the T1 and T2 treatments were significantly lower than those in the T3/T4 treatments. The soil organic carbon content in N2 was significantly higher; the soil C/N ratio was highest in N2, and T3 resulted in a significantly higher C/N ratio than T1 under the same N level; total soil respiration in N0 was significant lower, and T4 had higher respiration than T2 under the same N level. N addition increased Actinobacteriota, Chloroflexi, Thaumarchaeota, and Ascomycota, while decreaing Proteobacteria and Acidobacteriota. No reduction in fungal phylum was observed with nitrogen addition. N application significantly upregulated key enzymes in the pentose phosphate pathway (e.g., transketolase K00615, transaldolase K00616), while irrigation increased phosphoserine aminotransferase (K00831) abundance and decreased methylmalonyl-CoA mutase (K01848) abundance. N2T3 maintains high SOC content while achieving maximum yield, promoting soil fertility retention. Compared to T4, N2T3 also enhances water use efficiency. The N2T3 treatment (high N and grain filling stage irrigation) achieved the optimal balance between high wheat yield and SOC sequestration. Full article
(This article belongs to the Section Water Use and Irrigation)
19 pages, 311 KB  
Review
From Pandemic to Practice: How COVID-19 Has Reshaped Haemostasis in Cardiac Surgery: A Narrative Review
by Lydia Wilkinson, Arian Arjomandi Rad, Joshua Oliver and Antonios Kourliouros
J. Clin. Med. 2025, 14(22), 8109; https://doi.org/10.3390/jcm14228109 (registering DOI) - 16 Nov 2025
Abstract
The utilisation of cardiopulmonary bypass (CPB) during cardiac surgery is often associated with complex haemostatic perturbations, frequently manifesting as a paradoxical risk of both bleeding and thrombosis. This is postulated to be driven by systemic inflammation, endothelial activation and contact activation of the [...] Read more.
The utilisation of cardiopulmonary bypass (CPB) during cardiac surgery is often associated with complex haemostatic perturbations, frequently manifesting as a paradoxical risk of both bleeding and thrombosis. This is postulated to be driven by systemic inflammation, endothelial activation and contact activation of the coagulation cascade due to extracorporeal circulation. However, the coronavirus disease 2019 (COVID-19) pandemic revealed a unique hypercoagulable state, termed COVID-19-associated coagulopathy (CAC), also observed in those vaccinated against COVID-19. CAC displays similar physiological manifestations to those of disseminated intravascular coagulation (DIC), characterised by elevated fibrinogen and D-dimer values. The precise pathogenesis of CAC requires further elucidation though proposed mechanisms include: an exaggerated inflammatory response to COVID-19 infection or antibody proliferation due to vaccination, direct epithelial cell damage mediated by angiotensin converting enzyme 2, and ‘hypoxithrombosis’. CAC has since provided a unique framework to understand and potentially mitigate coagulation complications encountered during CPB in the post-pandemic era, as it is no longer sufficient to view COVID-19 as a transient influence on surgical risk. Rather, it must be recognized as a persistent modifier of the haemostatic environment across the population, with direct implications upon patient selection, intraoperative management and postoperative care in cardiac surgery. This review examines the pathological drivers behind CAC alongside the insights obtained from CAC management during ECMO deployment, to investigate the potential translation of such knowledge into improved anticoagulation strategies and monitoring during cardiac surgery. The use of alternative anticoagulants including factor XI inhibitors and the modulation of heparinase activity offers promising avenues to attenuate coagulopathies more commonly observed during CPB in the post-pandemic climate, whilst anti-Xa assays and viscoelastic testing have offered applicability to modern perfusion practices. By bridging the knowledge gained during the pandemic with that of conventional CPB, this review aims to inform future strategies for haemostasis management in cardiac surgery in a novel cohort of surgical patients. Full article
(This article belongs to the Section Cardiology)
42 pages, 1764 KB  
Review
Epigenetic Regulation of Salt Stress Responses in Rice: Mechanisms and Prospects for Enhancing Tolerance
by Emanuela Talarico, Eleonora Greco, Francesco Guarasci, Fabrizio Araniti, Adriana Chiappetta and Leonardo Bruno
Epigenomes 2025, 9(4), 46; https://doi.org/10.3390/epigenomes9040046 (registering DOI) - 16 Nov 2025
Abstract
Rice (Oryza sativa L.) is a staple food for over half the global population and a model organism for monocot plant research. However, it is susceptible to salinity, with most cultivated varieties showing reduced growth at salt levels above 3 dS/m. Despite [...] Read more.
Rice (Oryza sativa L.) is a staple food for over half the global population and a model organism for monocot plant research. However, it is susceptible to salinity, with most cultivated varieties showing reduced growth at salt levels above 3 dS/m. Despite numerous efforts to improve its salt tolerance, little progress has been made. A promising area of research lies in the study of epigenetic regulation, which encompasses DNA methylation, histone modifications, and chromatin remodelling. These processes play a crucial role in mediating how plants respond to salt stress by modulating gene expression. This often results in heritable changes that can be used as molecular markers. Studies in rice and other cereals have demonstrated a clear association between histone alterations, shifts in DNA methylation patterns, and the expression of salt-responsive genes. Furthermore, epigenetic mechanisms contribute to the development of stress memory, enabling plants to respond more effectively to recurring stressful conditions. Understanding these regulatory pathways offers new opportunities for breeding or engineering salt-tolerant rice varieties, potentially leading to improved crop resilience and productivity under saline conditions. Full article
22 pages, 5276 KB  
Article
Crystal-Chemical Evolution of Muscovite and Nb–Ta–Y–REE-Bearing Minerals in the Wadi Al-Baroud Granite–Pegmatite System
by Mabrouk Sami, Ioan V. Sanislav, Avish A. Kumar, Mostafa R. Abukhadra, Vandi Dlama Kamaunji and Suhail S. Alhejji
Minerals 2025, 15(11), 1206; https://doi.org/10.3390/min15111206 (registering DOI) - 16 Nov 2025
Abstract
The Wadi Al-Baroud granite–pegmatite system in the Eastern Desert of Egypt displays a progressive rare-metal enrichment evident in the crystal chemistry of muscovite mica and associated Nb–Ta–Y–REE oxide minerals. EMP analyses demonstrate that pegmatite-hosted muscovite is systematically enriched in Si, Fe, Mg, and [...] Read more.
The Wadi Al-Baroud granite–pegmatite system in the Eastern Desert of Egypt displays a progressive rare-metal enrichment evident in the crystal chemistry of muscovite mica and associated Nb–Ta–Y–REE oxide minerals. EMP analyses demonstrate that pegmatite-hosted muscovite is systematically enriched in Si, Fe, Mg, and fluorine compared to its granitic counterpart, reflecting crystallization from volatile-rich, highly evolved melts. Columbite group minerals exhibit pronounced fractionation trends, with pegmatitic columbite showing Ta and Mn enrichment and a low Nb/Ta ratio, indicative of late-stage F- and H2O-rich melt evolution and advanced magmatic differentiation. Y–Nb–Ti oxides, especially fergusonite-Y and euxenite-Y, record exceptional enrichment in high-field-strength elements (HFSEs) and heavy rare earth elements (HREEs), further driven by structural focusing and fluid-mediated alteration. These crystal-chemical trends record an extreme fractional crystallization and magmatic–hydrothermal transition, wherein F-rich fluids modified early magmatic minerals and promoted the incorporation of Y, REEs, Th, and U into late-stage oxides. The data indicate a two-stage evolutionary model, in which rare-metal mineralization first occurred through primary magmatic crystallization within the granite, followed by fluid-driven re-equilibration in the pegmatites. This integrated mineral-chemical approach provides a clearer understanding of rare-metal enrichment processes in granite–pegmatite systems and offers refined criteria for identifying exploration targets for Nb, Ta, Y, and HREEs. Full article
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16 pages, 1775 KB  
Article
Algae-Derived C-Phycocyanin Mitigates AGE–RAGE-Induced ER Stress and Mitochondrial Apoptosis: Implications for Diabetes-Associated Neurodegeneration
by Mei Chou Lai, Wayne Young Liu, Yu-Cheng Tzeng and I-Min Liu
Int. J. Mol. Sci. 2025, 26(22), 11077; https://doi.org/10.3390/ijms262211077 (registering DOI) - 16 Nov 2025
Abstract
Impaired glucose metabolism elevates the risk of neurodegenerative diseases by activating the receptor for advanced glycation end products (RAGE), thereby promoting oxidative and endoplasmic reticulum (ER) stress that leads to neuronal apoptosis. C-phycocyanin (C-PC), a natural pigment–protein complex derived from algae, possesses potent [...] Read more.
Impaired glucose metabolism elevates the risk of neurodegenerative diseases by activating the receptor for advanced glycation end products (RAGE), thereby promoting oxidative and endoplasmic reticulum (ER) stress that leads to neuronal apoptosis. C-phycocyanin (C-PC), a natural pigment–protein complex derived from algae, possesses potent antioxidant and antiglycation properties; however, its capacity to modulate RAGE-mediated neurotoxicity remains to be fully elucidated. In this study, we established a RAGE-driven neuronal injury model by exposing differentiated SH-SY5Y cells to advanced glycation end products (AGEs; 300 μg/mL). Pretreatment with C-PC (15–50 μmol/L) improved cell viability, preserved neuronal morphology, and attenuated AGEs-induced oxidative stress, as indicated by reduced intracellular reactive oxygen species and mitochondrial superoxide levels. Furthermore, C-PC inhibited activation of the PERK-CHOP pathway, and upregulated Bcl-2 while downregulating Bax, thereby preventing cytochrome c release and reducing caspase-9/3 activation as well as apoptotic DNA fragmentation. These neuroprotective effects of C-PC were comparable to those observed with the selective RAGE antagonist FPS-ZM1. In conclusion, our findings demonstrate that C-PC confers robust protection against AGEs-induced neuronal injury by suppressing oxidative and ER stress pathways downstream of RAGE activation, highlighting its potential as a natural modulator of the AGE–RAGE axis for the prevention or treatment of diabetes-associated neurodegeneration. Full article
18 pages, 3677 KB  
Article
FvIAA16 and FvIAA17: Two Aux/IAA Family Genes Positively Regulate Fruit Ripening in Strawberry
by Zhengrong Dai, Shiqi Shu, Wei Wang, Jiahan Shou, Shouzheng Lv, Yunfan Sun, Yanna Shi and Kunsong Chen
Horticulturae 2025, 11(11), 1381; https://doi.org/10.3390/horticulturae11111381 (registering DOI) - 16 Nov 2025
Abstract
Aux/IAA genes, functioning as transcriptional regulators downstream of auxin signaling, are essential for plant growth and development. However, their roles in fruit ripening remain largely undefined in strawberry. This study aims to elucidate the role of Aux/IAA genes in strawberry ripening. We identified [...] Read more.
Aux/IAA genes, functioning as transcriptional regulators downstream of auxin signaling, are essential for plant growth and development. However, their roles in fruit ripening remain largely undefined in strawberry. This study aims to elucidate the role of Aux/IAA genes in strawberry ripening. We identified 22 Aux/IAA family members and performed comprehensive spatiotemporal expression and hormone response analyses. Among them, FvIAA16 and FvIAA17 emerged as strong candidates associated with fruit ripening. Transient overexpression of FvIAA16 and FvIAA17 upregulated the expression of multiple ripening-related genes, leading to anthocyanin accumulation, soluble sugar enrichment, organic acid homeostasis, and furanone production. Dual-luciferase assays further demonstrated that both proteins robustly activated the promoters of ripening-related genes such as FvCHI and FvCHS. This activation was further enhanced by dimerization of the two proteins. Collectively, these findings reveal important regulatory functions of FvIAA16 and FvIAA17 in strawberry fruit ripening and offer valuable clues for further elucidating the molecular mechanisms underlying auxin-mediated ripening regulation. Full article
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18 pages, 1243 KB  
Article
Human OAT1, OAT3, OAT4 and OATP1A2 Facilitate the Renal Accumulation of Ochratoxin A
by Anish Mahadeo, Yik Pui Tsang, Angela R. Zheng, Sydney Arnzen, Acilegna G. Rodriguez, Mark S. Warren, Zsuzsanna Gáborik and Edward J. Kelly
Pharmaceutics 2025, 17(11), 1474; https://doi.org/10.3390/pharmaceutics17111474 (registering DOI) - 16 Nov 2025
Abstract
Background/Objectives: Ochratoxin A (OTA) is a widespread foodborne mycotoxin linked to chronic kidney disease of unknown etiology. Despite evidence from animal models showing OTA accumulation in the kidney, the molecular mechanisms underlying its renal disposition in humans remain only partially understood. Here, [...] Read more.
Background/Objectives: Ochratoxin A (OTA) is a widespread foodborne mycotoxin linked to chronic kidney disease of unknown etiology. Despite evidence from animal models showing OTA accumulation in the kidney, the molecular mechanisms underlying its renal disposition in humans remain only partially understood. Here, we identify human renal transporters responsible for OTA kidney accumulation, elimination, and establish Michaelis–Menten kinetics under matched conditions to directly compare transport mechanisms. We also aim to identify inhibition potential of these transport mechanisms with common dietary polyphenols. Methods: Mammalian cells and membrane vesicles overexpressing human renal transporters were used to screen and profile the uptake and efflux of OTA. Miquelianin, (-)-Epicatechin-3-O-gallate, myricetin, luteolin, and caffeic acid were tested as potential concentration-dependent transporter inhibitors. Results: We demonstrate that OTA is a substrate for human organic anion transporter (hOAT) 1 (Km: 2.10 ± 0.50 μM, Vmax: 396.9 ± 27.0 pmol/mg/min), hOAT3 (Km: 2.58 ± 0.83 μM, Vmax: 141.4 ± 30.3 pmol/mg/min), hOAT4 (Km: 6.38 ± 1.45 μM, Vmax: 96.9 ± 18.8 pmol/mg/min), and human organic anion transporting polypeptide (hOATP) 1A2 (Km: 37.3 ± 6.2 μM, Vmax: 801.0 ± 133.9 pmol/mg/min). Among efflux transporters, OTA was transported only by human breast cancer resistance protein (hBCRP), which has minimal renal expression. While none of the uptake transporters were potently inhibited (>90%) by polyphenols at 10 μM, luteolin inhibited hBCRP-mediated transport of OTA with an IC50 of 22 μM and caffeic acid stimulated hBCRP-mediated efflux with an EC50 of 713.8 μM, both of which are physiologically relevant intestinal lumen concentrations. Conclusions: Our results confirm that exposure to OTA will lead to renal accumulation and increased health risks in affected populations, necessitating increased scrutiny of our food sources. Full article
(This article belongs to the Section Drug Targeting and Design)
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15 pages, 2346 KB  
Article
Effects of Sleeve Gastrectomy on Blood Pressure Reduction in Diet-Induced Obese Hypertensive Rats: A Potential Role of Prouroguanylin
by Naoki Matsuda, Yuichi Yoshida, Koro Gotoh, Satoshi Nagai, Ryo Kurimoto, Kentaro Sada, Takaaki Noguchi, Miho Suzuki, Shotaro Miyamoto, Yoshinori Ozeki, Takashi Ozaki, Akiko Kudo, Takeshi Nakata, Akihiro Fukuda, Takayuki Masaki and Hirotaka Shibata
Nutrients 2025, 17(22), 3581; https://doi.org/10.3390/nu17223581 (registering DOI) - 16 Nov 2025
Abstract
Background/Objectives: Sleeve gastrectomy (SG) is the most commonly performed bariatric surgery worldwide. It results in significant weight loss and improves metabolic disorders such as hypertension. Weight loss is thought to be the main factor contributing to blood pressure (BP) reduction after SG. Small-intestinal [...] Read more.
Background/Objectives: Sleeve gastrectomy (SG) is the most commonly performed bariatric surgery worldwide. It results in significant weight loss and improves metabolic disorders such as hypertension. Weight loss is thought to be the main factor contributing to blood pressure (BP) reduction after SG. Small-intestinal hormones may also mediate the antihypertensive effects of SG. We aimed to investigate the mechanisms underlying the antihypertensive effects of SG through small-intestinal hormones independently of weight loss. Methods: This study involved male Sprague–Dawley rats that underwent a sham operation or SG, followed by a dietary intervention involving a standard diet, a high-fat and high-salt diet, or pair-feeding with SG. Results: Three weeks postoperatively, SG significantly reduced systolic blood pressure (SBP) and increased urinary sodium excretion. RNA sequencing of the small intestine revealed upregulation of the gene encoding prouroguanylin (proUGN). proUGN is a small-intestinal hormone that inhibits renal sodium reabsorption by converting sodium/hydrogen ion exchanger type 3 (NHE3) in the proximal tubules into the inactive phosphorylated form at Ser552 (pS552-NHE3). Furthermore, SG significantly increased proUGN levels in the ileum and plasma, as well as the levels of pS552-NHE3 in the renal cortex. The administration of exogenous uroguanylin, which is converted from proUGN, resulted in increased renal pS552-NHE3, increased urinary sodium excretion, and decreased SBP without body weight reduction. These effects were similar to those observed with SG. Conclusions: SG increases proUGN secretion from the small intestine, leading to increased blood concentration. This inhibits NHE3 activity in the proximal tubules, promotes natriuresis and reduces BP. Full article
(This article belongs to the Special Issue Featured Articles on Nutrition and Obesity Management (3rd Edition))
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17 pages, 931 KB  
Review
The Effect of Maternal Stress on 11beta-Hydroxysteroid Dehydrogenase Activity During Pregnancy: Evidence for Potential Pregnancy Complications and Consequences on Fetal Development and Metabolism
by Polina Pavli, George Mastorakos, Makarios Eleftheriades and Georgios Valsamakis
Int. J. Mol. Sci. 2025, 26(22), 11071; https://doi.org/10.3390/ijms262211071 (registering DOI) - 16 Nov 2025
Abstract
Τhe intrauterine environment has a strong connection with the growing fetus and possible effects that can continue up to adulthood. Currently, stress is conceptualized as a modern teratogen. The overwhelming majority of studies indicate that maternal stress during pregnancy may have effects on [...] Read more.
Τhe intrauterine environment has a strong connection with the growing fetus and possible effects that can continue up to adulthood. Currently, stress is conceptualized as a modern teratogen. The overwhelming majority of studies indicate that maternal stress during pregnancy may have effects on pregnancy outcomes and fetal development, with long-lasting consequences on child and adult vulnerability to disease. Glucocorticoids are essential for regulating fetal development, growth, and metabolism. The two isoforms of 11beta-hydroxysteroid dehydrogenase enzyme (11β-HSD) mediate and regulate glucocorticoid actions and biological activity. It has not yet been fully elucidated whether maternal stress during pregnancy affects 11β-HSD isoenzyme activity and expression and results in possible adverse effects on fetal development, metabolism, and pregnancy outcomes. This review examines a possible pathophysiological mechanism by which maternal stress during pregnancy affects placental 11β-HSD isoenzyme activity, thereby causing adverse effects on the physiological status of pregnancy, fetal development, and metabolism. Furthermore, the main outcome of the review is the following: chronic and acute maternal stress during pregnancy affects the activity and the expression of placental 11β-HSD isoenzymes and has possible subsequent unfavorable results on preeclampsia, preterm birth, and fetuses with intrauterine growth restriction (IUGR) or small for gestational age (SGA) fetuses. Full article
(This article belongs to the Special Issue Endocrinology of Pregnancy)
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17 pages, 2290 KB  
Article
Comparative Analysis of Amino Acid, Sugar, Acid and Volatile Compounds in 4-CPA-Treated and Oscillator-Pollinated Cherry Tomato Fruits During Ripe Stage
by Zhimiao Li, Sihui Guan, Meiying Ruan, Zhuping Yao, Chenxu Liu, Hongjian Wan, Qingjing Ye, Yuan Cheng and Rongqing Wang
Foods 2025, 14(22), 3914; https://doi.org/10.3390/foods14223914 (registering DOI) - 15 Nov 2025
Abstract
4-Chlorophenoxyacetic acid (4-CPA) is an auxin-type plant growth regulator widely used in fruit and vegetable production. However, its influence on the nutritional and sensory qualities of horticultural crops remains insufficiently characterized. This study investigated the influence of 4-CPA application and oscillator-mediated pollination on [...] Read more.
4-Chlorophenoxyacetic acid (4-CPA) is an auxin-type plant growth regulator widely used in fruit and vegetable production. However, its influence on the nutritional and sensory qualities of horticultural crops remains insufficiently characterized. This study investigated the influence of 4-CPA application and oscillator-mediated pollination on the metabolic composition of fully ripe fruits of Solanum lycopersicum var. cerasiforme cv. ‘Zheyingfen No. 1’. Two concentrations of 4-CPA (16 mg/L and 8 mg/L) were applied during flowering, and their effects on amino acids, soluble sugars, organic acids, and volatile compounds (VOCs) were comparatively analyzed. The results indicated that treatment with 8 mg/L 4-CPA treatment significantly increased the total amino acid content in ripe fruits compared with the control and the 16 mg/L treatment. Among the 17 amino acids identified, the contents of umami-related amino acids, including glutamic acid (Glu) and aspartic acid (Asp), were markedly enhanced. In particular, Glu content in the C8 treatment was the highest and accounted for more than 50% of the total amino acid content. The accumulation of sugars was not significantly affected by 4-CPA treatment, while the C8 treatment resulted in the lowest level of total organic acids, which are crucial for flavor development at the ripening stage. A 29.35% increase in VOCs was observed” for conciseness in 4-CPA-treated fruits compared with the control. Analysis of relative odor activity values (rOAVs) showed that although 4-CPA treatment reduced the number of aroma-active compounds, it promoted the accumulation of β-ionone, thereby shifting the tomato fruit aroma profile toward floral, woody, sweet, and fruity notes. In summary, 4-CPA treatment regulated the nutritional and flavor quality of ripe cherry tomato fruits by increasing the content of Glu and other amino acids, enhancing the diversity of VOCs, and promoting the formation of key aroma-active substances such as β-ionone. Full article
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