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19 pages, 4961 KB  
Article
Ferrate-Modified Biochar Boosts Ryegrass Phytoremediation of Petroleum and Zinc Co-Contaminated Soils
by Xinyu Wang, Guodong Zheng, Zhe Liu and Jie Li
Processes 2025, 13(9), 2827; https://doi.org/10.3390/pr13092827 - 3 Sep 2025
Abstract
Phytoremediation is widely acknowledged as a viable method for soil remediation; however, its efficacy remains limited in soils co-polluted with petroleum hydrocarbons and heavy metals. To overcome this constraint, the present study explored an innovative approach utilizing ferrate-modified biochar (FeBC) to augment phytoremediation [...] Read more.
Phytoremediation is widely acknowledged as a viable method for soil remediation; however, its efficacy remains limited in soils co-polluted with petroleum hydrocarbons and heavy metals. To overcome this constraint, the present study explored an innovative approach utilizing ferrate-modified biochar (FeBC) to augment phytoremediation efficiency. Experimental findings revealed that ferrate treatment markedly modified the physicochemical characteristics of biochar, yielding thinner, smoother-surfaced structures with pronounced iron enrichment. At a 5% application rate alongside ryegrass cultivation, FeBC exhibited superior remediation performance, achieving 52.0% degradation of petroleum hydrocarbons (notably within the meso-aggregate fraction) and a 19.2% decline in zinc bioavailability via immobilization, thereby reducing zinc uptake in ryegrass tissues. Furthermore, FeBC amendment induced significant shifts in rhizosphere soil biochemistry and microbial ecology, characterized by diminished catalase activity but elevated urease and alkaline phosphatase activities. Phospholipid fatty acid profiling indicated a substantial rise in bacterial biomass (encompassing both Gram-positive and Gram-negative groups), particularly in meso- and micro-aggregates, whereas soil bacterial α-diversity declined markedly, accompanied by distinct compositional changes across aggregate size fractions. These results offer mechanistic insights into the synergistic interaction between FeBC and ryegrass in co-contaminated soil rehabilitation, the aggregate-dependent distribution of remediation effects, and microbial community adaptations to FeBC treatment. Collectively, this study advances the understanding of ferrate-modified biochar’s role in phytoremediation enhancement and clarifies its operational mechanisms in petroleum-zinc co-contaminated soil systems. Full article
20 pages, 7627 KB  
Article
Genome-Wide Identification of Cysteine-Rich Polycomb-like Protein (CPP) Gene Family and Their Expression Profile Analysis in Stem Lettuce (Lactuca sativa)
by Min Zhu, Le Jiang, Zhiheng Chen, Ping Xu, Chao Wang, Quanyan Zhang, Mengyao Li and Ying Huang
Agronomy 2025, 15(9), 2120; https://doi.org/10.3390/agronomy15092120 - 3 Sep 2025
Abstract
Cysteine-rich polycomb-like protein (CPP) transcription factors (TFs) play critical roles in the process of plant growth and development, as well as stress responses. To date, no reports about CPP TFs have been published for lettuce (Lactuca sativa). In this study, six [...] Read more.
Cysteine-rich polycomb-like protein (CPP) transcription factors (TFs) play critical roles in the process of plant growth and development, as well as stress responses. To date, no reports about CPP TFs have been published for lettuce (Lactuca sativa). In this study, six CPP TFs (LsCPP1-LsCPP6) were identified in lettuce. Phylogenetic analysis showed that LsCPP TFs were classified into two clades (Clade I and Clade II). Six LsCPP genes were distributed across four chromosomes. Cis-elements, which are involved in environmental stress, hormone response, and development processes, were identified in the promoters of LsCPP genes. LsCPP genes were induced by different tissues and the stem enlargement processes of stem lettuce. Plant hormones (SA, ABA) and abiotic stress (salt, drought) induced the expression of LsCPP genes. LsCPP4 was significantly induced after drought stress for 12 h. Notably, the expression level of LsCPP4 increased more than 10 times (12 h) and 150 times (24 h) after salt stress. ABA and SA significantly induced the expression profile of LsCPP6. This study not only provides the basis for future functional research of LsCPP genes, particularly their roles in lettuce stress resistance, but also provides a foundation for molecular breeding to enhance the agricultural traits in lettuce. Full article
29 pages, 585 KB  
Review
Beyond the BMI Paradox: Unraveling the Cellular and Molecular Determinants of Metabolic Health in Obesity
by Kyoichiro Tsuchiya and Takahiro Tsutsumi
Biomolecules 2025, 15(9), 1278; https://doi.org/10.3390/biom15091278 - 3 Sep 2025
Abstract
Obesity has traditionally been considered a major risk factor for numerous metabolic disorders and diseases. However, a subset of individuals with obesity, classified as having “metabolically healthy obesity” (MHO), display relatively normal metabolic parameters despite excess adiposity. This review critically examines the current [...] Read more.
Obesity has traditionally been considered a major risk factor for numerous metabolic disorders and diseases. However, a subset of individuals with obesity, classified as having “metabolically healthy obesity” (MHO), display relatively normal metabolic parameters despite excess adiposity. This review critically examines the current knowledge surrounding MHO, including its various definitions, prevalence, clinical characteristics, contributing factors, and long-term outcomes. While MHO carries lower health risks compared to metabolically unhealthy obesity (MUO), evidence consistently demonstrates increased disease risk compared to metabolically healthy normal-weight individuals, particularly for type 2 diabetes, cardiovascular disease, chronic kidney disease, and certain cancers. MHO prevalence ranges from 10 to 30% among individuals with obesity globally, varying by sex, age, BMI, and ethnicity. Multiple factors contribute to the MHO phenotype, including beneficial adipose tissue distribution patterns, enhanced adipocyte function, favorable genetic profiles, and lifestyle factors. Recent single-cell transcriptomic analyses have identified specific cell populations, particularly mesothelial cells, as key drivers of metabolic health in visceral adipose tissue. The discovery of persistent epigenetic memory of obesity provides molecular evidence for why MHO often represents a transient state, with many individuals progressing to MUO over time. Emerging evidence also reveals differential therapeutic responses to GLP-1 receptor agonists between MHO and MUO phenotypes, highlighting the need for precision medicine approaches. The concept of MHO has important clinical implications for risk stratification and personalized treatment approaches. This review synthesizes current evidence while highlighting knowledge gaps and future research directions in this rapidly evolving field. Full article
(This article belongs to the Section Molecular Medicine)
23 pages, 1432 KB  
Review
The Sex Hormone Precursors Dehydroepiandrosterone (DHEA) and Its Sulfate Ester Form (DHEAS): Molecular Mechanisms and Actions on Human Body
by Hsin-Yi Lin, Jie-Hong Chen and Kuo-Hu Chen
Int. J. Mol. Sci. 2025, 26(17), 8568; https://doi.org/10.3390/ijms26178568 (registering DOI) - 3 Sep 2025
Abstract
Dehydroepiandrosterone (DHEA) and its sulfate ester form DHEAS, are multifunctional steroid hormones primarily produced in the adrenal cortex, with additional synthesis in peripheral tissues. DHEA/DHEAS serve as precursors to sex steroids and exhibit neuroprotective, anti-inflammatory, and immune-modulating effects. DHEA levels decline significantly with [...] Read more.
Dehydroepiandrosterone (DHEA) and its sulfate ester form DHEAS, are multifunctional steroid hormones primarily produced in the adrenal cortex, with additional synthesis in peripheral tissues. DHEA/DHEAS serve as precursors to sex steroids and exhibit neuroprotective, anti-inflammatory, and immune-modulating effects. DHEA levels decline significantly with age, a phenomenon termed “adrenopause,” prompting interest in supplementation to mitigate age-related symptoms. Particularly in postmenopausal women, DHEA has shown potential benefits in treating genitourinary syndrome of menopause (GSM), including improved vaginal health, lubrication, and sexual function. While intravaginal DHEA appears effective and safer than systemic estrogen therapy, especially for women with estrogen sensitivity, results remain mixed for oral administration. DHEA and DHEAS exhibit diverse neuroactive properties through modulation of GABA-A, NMDA, and sigma-1 receptors. These neurosteroids contribute to neuroprotection, synaptic plasticity, and mood regulation. Altered DHEA/DHEAS levels have been implicated in neurodegenerative disorders and depression, with emerging evidence supporting their potential therapeutic value. In addition, DHEA plays a multifaceted role in aging-related physiological changes. It supports muscle anabolism, bone density maintenance, cardiovascular protection, and immune regulation. Though supplementation shows potential benefits, especially in conjunction with resistance training, results remain discrepant. Current evidence has revealed that the therapeutic effects of DHEA supplementation are inconsistent in different human systems among different studies. The diversity of results is mainly due to heterogeneous receptor distribution, various action pathways, and distinct tissue responses in different systems. Further research is needed to define its efficacy and dosage across various systems. Full article
22 pages, 2870 KB  
Review
Two Approaches to Solid-State NMR of Mobile Molecules in Nanoporous Materials
by Alexander Panich
Molecules 2025, 30(17), 3603; https://doi.org/10.3390/molecules30173603 - 3 Sep 2025
Abstract
This paper reviews two solid-state NMR approaches for investigating mobile molecules in nanoporous materials, with a focus on the motion-averaged dipole–dipole interactions of nuclear spins. The first approach addresses intramolecular dipole–dipole interactions, where the anisotropic molecular motion in solids leads to partially averaged [...] Read more.
This paper reviews two solid-state NMR approaches for investigating mobile molecules in nanoporous materials, with a focus on the motion-averaged dipole–dipole interactions of nuclear spins. The first approach addresses intramolecular dipole–dipole interactions, where the anisotropic molecular motion in solids leads to partially averaged interactions that reflect the spatial distribution of molecular positions during motion. The second approach examines intermolecular dipole–dipole interactions, which produce anisotropic features in NMR spectra and affect nuclear spin relaxation due to the Brownian motion of molecules within non-spherical nanoscale pores. The applicability of these methods is considered for systems exhibiting molecular mobility, including zeolites, collagen tissues, intercalation compounds, and plant stems. Full article
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19 pages, 584 KB  
Article
Brain Metabolism of Allopregnanolone and Isoallopregnanolone in Male Rat Brain
by Charlotte Öfverman, Martin Hill, Maja Johansson and Torbjörn Bäckström
Int. J. Mol. Sci. 2025, 26(17), 8559; https://doi.org/10.3390/ijms26178559 (registering DOI) - 3 Sep 2025
Abstract
Allopregnanolone (allo) and isoallopregnanolone (isoallo) are neuroactive steroid epimers that differ in hydroxyl orientation at carbon three. Allo is a potent GABA-A receptor agonist, while isoallo acts as an antagonist, influencing brain function through their interconversion. Their metabolism varies across brain regions due [...] Read more.
Allopregnanolone (allo) and isoallopregnanolone (isoallo) are neuroactive steroid epimers that differ in hydroxyl orientation at carbon three. Allo is a potent GABA-A receptor agonist, while isoallo acts as an antagonist, influencing brain function through their interconversion. Their metabolism varies across brain regions due to enzyme distribution, with AKR1C1–AKR1C3 active in the brain and AKR1C4 restricted to the liver. In rats, AKR1C9 (liver) and AKR1C14 (intestine) perform similar roles. Beyond AKR1Cs, HSD17Bs regulate steroid balance, with HSD17B6 active in the liver, thyroid, and lung, while HSD17B10, a mitochondrial enzyme, influences metabolism in high-energy tissues. Our current data obtained using the GC-MS/MS platform show that allo and isoallo in rats undergo significant metabolic conversion, suggesting a regulatory role in neurosteroid action. High allo levels following isoallo injection indicate brain interconversion, while isoallo clears more slowly from blood and undergoes extensive conjugation. Metabolite patterns differ between brain and plasma—allo injection leads to 5α-DHP and isoallo production, whereas isoallo treatment primarily yields allo. Human plasma contains mostly sulfate/glucuronided steroids (2.4–6% non-sulfate/glucuronided), whereas male rats exhibit much higher free steroid levels (29–56%), likely due to the absence of zona reticularis. These findings highlight tissue-specific enzymatic differences, which may impact neurosteroid regulation and CNS disorders. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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16 pages, 2586 KB  
Article
New Characterization of Lipedema Stages: Focus on Pain, Water, Fat and Skeletal Muscle
by Sara Al-Ghadban, Jane V. Evancio, Paula E. F. Alfiscar and Karen L. Herbst
Life 2025, 15(9), 1397; https://doi.org/10.3390/life15091397 - 3 Sep 2025
Abstract
Lipedema is a chronic, progressive adipose connective tissue disorder characterized by symmetrical, disproportionate fat accumulation, typically affecting the lower extremities and arms, accompanied by pain, swelling, and a sensation of heaviness. This study introduces intermediate Stages 1.5 and 2.5 to the established lipedema [...] Read more.
Lipedema is a chronic, progressive adipose connective tissue disorder characterized by symmetrical, disproportionate fat accumulation, typically affecting the lower extremities and arms, accompanied by pain, swelling, and a sensation of heaviness. This study introduces intermediate Stages 1.5 and 2.5 to the established lipedema classification (Stages 1, 2 and 3), and other affected areas, based on physical examination, a questionnaire, and photographic documentation. Bioelectrical Impedance Spectroscopy (BIS) was employed to quantify total body water (TBW) across stages. A significant and linear increase in BMI was observed from Stage 1 to 3, correlating with increased reported pain and heaviness in the thighs, calves, and upper arms. Systemic symptoms of brain fog, debilitating fatigue, and hypothermia were significantly prevalent. TBW demonstrated a significant, stage-dependent increase in the lower extremities. Adipose tissue accumulation over the knees and feet significantly increased with lipedema stage. In contrast, shin involvement was evident in early stages and remained consistently elevated throughout later stages. Skeletal Muscle Mass (SMM) exhibited a significant increase across lipedema stages, positively correlating with fat mass (FM) in Stage 3. This study elucidates previously underrecognized clinical features and distribution patterns of lipedema, offering a refined staging system to improve understanding of its progression and burden. Full article
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23 pages, 2481 KB  
Article
Comparison of the Effects of Exogenous Selenium and Silicon on Alleviating Cadmium Stress in Artemisia argyi
by Yaxin Yu, Yu Guo, Qianqian Yu, Mengting Wu and Wenfang Hao
Agronomy 2025, 15(9), 2114; https://doi.org/10.3390/agronomy15092114 - 2 Sep 2025
Abstract
Selenium (Se) and silicon (Si) have been demonstrated to mitigate the adverse effects of cadmium (Cd) stress on the growth of various higher plants. However, the distinct mechanisms by which Se and Si, when applied to soil, alleviate the toxicity of Artemisia argyi [...] Read more.
Selenium (Se) and silicon (Si) have been demonstrated to mitigate the adverse effects of cadmium (Cd) stress on the growth of various higher plants. However, the distinct mechanisms by which Se and Si, when applied to soil, alleviate the toxicity of Artemisia argyi under Cd stress remain unclear. This study employed A. argyi as the experimental material and simulated a Cd stress environment in soil pot experiments by adding CdCl2·2.5H2O at concentrations of 4 mg kg−1 and 10 mg kg−1. Exogenous Se in the form of Na2SeO3 (2 mg kg−1) or Si in the form of Na2SiO3 (20 mg kg−1) was applied simultaneously. After 90 days of combined exposure, the study investigated the differential mechanisms by which Se and Si application influenced Cd uptake by roots, its translocation within aboveground and underground tissues, and the antioxidant system of A. argyi under two levels of Cd stress. The results indicate that under Cd stress conditions, the application of Se significantly promotes the growth of A. argyi. Under both Cd concentration treatments, the application of Se or Si alone markedly reduces the Cd content in the aboveground parts of A. argyi. This reduction may be attributed to alterations in the subcellular distribution of Cd, decreased Cd content in organelles, and increased Cd sequestration in cell walls and soluble components. Furthermore, the application of Se or Si in soil can enhance the content of osmoregulatory substances, chlorophyll, and plant chelating agents in A. argyi leaves while reducing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), particularly at high Cd concentrations. The findings suggest that the alleviation of Cd toxicity by exogenous Se is primarily due to its role in inhibiting Cd uptake and translocation to shoots, as well as strengthening Cd compartmentalization in root cell walls and enhancing the antioxidant defense system. In contrast, exogenous Si primarily mitigates Cd toxicity by restricting Cd translocation from underground to aboveground plant tissues. Full article
(This article belongs to the Section Plant-Crop Biology and Biochemistry)
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18 pages, 2564 KB  
Article
Global Profiling of Protein β-hydroxybutyrylome in Porcine Liver
by Shuhao Fan, Jinyu Guan, Fang Tian, Haibo Ye, Qianqian Wang, Lei Lv, Yuanyuan Liu, Xianrui Zheng, Zongjun Yin and Xiaodong Zhang
Biology 2025, 14(9), 1183; https://doi.org/10.3390/biology14091183 - 2 Sep 2025
Abstract
The liver orchestrates metabolic homeostasis through dynamic post-translational modifications. β-hydroxybutyrylation (Kbhb), a ketone body-driven modification, regulates epigenetics and metabolism in humans and mice but remains unexplored in livestock. Here, we characterize the porcine hepatic β-hydroxybutyrylome using high-resolution mass spectrometry, identifying 4982 Kbhb sites [...] Read more.
The liver orchestrates metabolic homeostasis through dynamic post-translational modifications. β-hydroxybutyrylation (Kbhb), a ketone body-driven modification, regulates epigenetics and metabolism in humans and mice but remains unexplored in livestock. Here, we characterize the porcine hepatic β-hydroxybutyrylome using high-resolution mass spectrometry, identifying 4982 Kbhb sites on 2122 proteins—the largest dataset to date. β-hydroxybutyrylation predominantly targets non-histone proteins (99.68%), with enrichment in fatty acid β-oxidation, TCA cycle, and oxidative phosphorylation pathways. Subcellular localization revealed cytoplasmic (38.1%), mitochondrial (18.1%), and nuclear (15.3%) dominance, reflecting BHB-CoA synthesis sites. Motif analysis identified conserved leucine, phenylalanine, and valine residues at modified lysines, suggesting enzyme-substrate specificity. β-hydroxybutyrate treatment elevated global Kbhb levels, increasing TCA intermediates (e.g., α-ketoglutarate, +9.56-fold) while reducing acetyl-CoA, indicating enhanced mitochondrial flux. Cross-species comparisons showed tissue-specific Kbhb distribution (nuclear in human cells vs. mitochondrial in mice), highlighting metabolic adaptations. This study establishes pigs as a model for Kbhb research, linking it to energy regulation and providing insights into metabolic reprogramming. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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31 pages, 6830 KB  
Article
Genome-Wide Identification and Expression Analysis of the Growth Regulatory Factor (GRF) and Growth-Regulating Interacting Factor (GIF) Gene Families in Cassava
by Rou Xu, Tianyu Li, Linling Zheng, Yuhua Chen, Assane Hamidou Abdoulaye, Yating Feng, Wenlong Wen and Yinhua Chen
Horticulturae 2025, 11(9), 1046; https://doi.org/10.3390/horticulturae11091046 - 2 Sep 2025
Abstract
Growth regulatory factors (GRFs) and growth-regulating interacting factors (GIFs) play significant roles in plant growth, development, and environmental stress responses. Previous studies have reported the functions of GRF and GIF genes in model plants such as Arabidopsis and rice. [...] Read more.
Growth regulatory factors (GRFs) and growth-regulating interacting factors (GIFs) play significant roles in plant growth, development, and environmental stress responses. Previous studies have reported the functions of GRF and GIF genes in model plants such as Arabidopsis and rice. Nevertheless, the GRF and GIF genes remained unexplored in cassava. Cassava (Manihot esculenta Crantz) is an important tropical economic crop. Its starchy storage roots serve as a major source of food and industrial raw materials, while its protein-rich leaves are widely consumed as leafy vegetables in Africa and other regions, offering high nutritional value and significant horticultural potential. This study identified 28 MeGRFs distributed on 13 chromosomes and 5 MeGIFs on 4 chromosomes through bioinformatic analysis and expression profiling. Promoter analysis uncovered cis-acting elements associated with growth, hormone signaling, and biotic stress responses. Under different tissues and biotic (e.g., cassava bacterial blight, CBB) and abiotic (e.g., drought, low temperature) stress conditions, GRF and GIF genes exhibited differential expression patterns. Real-time quantitative PCR analysis showed a significant expression for 11 MeGRFs and 3 MeGIFs under the Xanthomonas phaseoli pv. manihotis (Xpm) treatment. VIGS functional validation demonstrated that MeGRF28 and MeGIF4 could enhance cassava resistance to bacterial blight, and protein–protein interaction network analysis suggested that they may form a core GRF-GIF complex. This study provides a theoretical basis for understanding the functional evolution of the GRF and GIF gene families in cassava and their roles in horticultural trait development and stress resistance mechanisms. Full article
(This article belongs to the Special Issue Breeding by Design: Advances in Vegetables)
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20 pages, 3380 KB  
Article
A Pilot Study on Tissue Deformation Using an Integrated Sensor–Actuator Blood Collection Setup in Aquaculture (Salmo salar)
by Ishrak Siddiquee, Md Ebne Al Ashad and Ahmed Hasnain Jalal
Electronics 2025, 14(17), 3510; https://doi.org/10.3390/electronics14173510 - 2 Sep 2025
Abstract
This pilot study presents a sensor–actuator setup designed to evaluate tissue deformation in Atlantic Salmon (Salmo salar) during needle insertion. The system integrates three types of low-cost, commercially available force sensors to capture force profiles and identify biomechanical events associated with [...] Read more.
This pilot study presents a sensor–actuator setup designed to evaluate tissue deformation in Atlantic Salmon (Salmo salar) during needle insertion. The system integrates three types of low-cost, commercially available force sensors to capture force profiles and identify biomechanical events associated with tissue layer transitions. Controlled insertions were performed on a deceased specimen, and the resulting force data were analyzed to quantify insertion dynamics and estimate tissue deformation. A simulation model based on the recorded force values was developed to calculate stress distribution and deformation, which ranged from 0.001 µm to 8.4 µm and from 0.3 N/m2 to 4.9 N/m2, respectively. The results indicate minimal biomechanical disruption, supporting the feasibility of using sensor–actuator systems for minimally invasive procedures in aquaculture. Although biological responses such as inflammation and healing could not be assessed, this study lays the basis for future research involving live specimens and blood sampling. The findings carry important implications for fish welfare, offering a pathway toward ethical and automated sampling techniques in aquaculture and livestock applications. Full article
(This article belongs to the Section Computer Science & Engineering)
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28 pages, 7900 KB  
Article
Sublethal Doxorubicin Promotes Extracellular Vesicle Biogenesis in A375 Melanoma Cells: Implications for Vesicle-Loaded TGF-β-Mediated Cancer Progression and Cardiovascular Pathophysiology
by Laura Fernanda Fernández-Fonseca, Susana Novoa-Herrán, Adriana Umaña-Pérez and Luis Alberto Gómez-Grosso
Int. J. Mol. Sci. 2025, 26(17), 8524; https://doi.org/10.3390/ijms26178524 - 2 Sep 2025
Abstract
Doxorubicin (Dox) is not a first-line treatment for melanoma due to limited antitumor efficacy and dose-dependent cardiotoxicity. However, sublethal doses may trigger adaptive cellular responses that influence tumor progression and systemic toxicity. Small extracellular vesicles (EVs) are key mediators of intercellular communication and [...] Read more.
Doxorubicin (Dox) is not a first-line treatment for melanoma due to limited antitumor efficacy and dose-dependent cardiotoxicity. However, sublethal doses may trigger adaptive cellular responses that influence tumor progression and systemic toxicity. Small extracellular vesicles (EVs) are key mediators of intercellular communication and can carry bioactive molecules that modulate both the tumor microenvironment and distant tissues. This study investigates how sublethal Dox exposure alters EV biogenesis and cargo in A375 melanoma cells and explores the potential implications for cardiovascular function. We treated human A375 melanoma cells with 10 nM dox for 96 h. EVs were isolated using differential ultracentrifugation and size exclusion chromatography. Vesicle characterization included Immunocytochemistry for CD63, CD81, CD9, Rab7 and TSG101, scanning electron microscopy (SEM) Nanoparticle Tracking Analysis (NTA), and Western blotting for CD81 and CytC. We analyzed cytokine content using cytokine membrane arrays. Guinea pig cardiomyocytes were exposed to the isolated vesicles, and mitochondrial activity was evaluated using the MTT assay. Statistical analysis included t-tests, ANOVA, Cohen’s d, and R2 and η2. Dox exposure significantly increased EV production (13.6-fold; p = 0.000014) and shifted vesicle size distribution. CD81 expression was significantly upregulated (p = 0.0083), and SEM (microscopy) confirmed enhanced vesiculation. EVs from treated cells were enriched in TGF-β (p = 0.0134), VEGF, CXCL1, CXCL12, CCL5, IL-3, IL-4, IL-10, Galectin-3, and KITLG. Cardiomyocytes exposed to these vesicles showed a 2.3-fold reduction in mitochondrial activity (p = 0.0021), an effect absent when vesicles were removed. Bioinformatic analysis linked EV cargo to pathways involved in cardiac hypertrophy, inflammation, and fibrosis. As conclusion, sublethal Doxorubicin reprograms melanoma-derived EVs by enhancing their production and enriching their cargo with profibrotic and immunomodulatory mediators. These vesicles may contribute to tumor progression and cardiovascular physiopathology, suggesting that targeting EVs could improve therapeutic outcomes in cancer and cardiovascular disease. Full article
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12 pages, 698 KB  
Article
18F-FDG PET/CT Findings to Improve Confidence in Distinguishing Lung External Beam Radiotherapy Side Effects
by Dino Rubini, Valerio Nardone, Corinna Altini, Claudia Battisti, Cristina Ferrari, Alfonso Reginelli, Federico Gagliardi, Giuseppe Rubini and Salvatore Cappabianca
Life 2025, 15(9), 1392; https://doi.org/10.3390/life15091392 - 2 Sep 2025
Abstract
Modern external beam radiotherapy (EBRT) on lung cancer improved dose distribution thanks to advanced dose calculation algorithms, but side effects and relapses can occur in any case onset. Differential diagnosis of relapses and side effects is difficult, and when computed tomography (CT) is [...] Read more.
Modern external beam radiotherapy (EBRT) on lung cancer improved dose distribution thanks to advanced dose calculation algorithms, but side effects and relapses can occur in any case onset. Differential diagnosis of relapses and side effects is difficult, and when computed tomography (CT) is uncertain 18-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) can support the diagnosis, even if it can also be difficult to construe. The aim of this retrospective analysis was to evaluate 18F-FDG PET/CT qualitative patterns and semiquantitative parameters, both automatic and preceded by physicians, in interpreting lung lesions in the radiotherapy (RT) lung irradiation field. In total, 94 patients (pts) submitted to EBRT (3 months before) for stage II lung cancer were included (74 men, 20 women, mean age of 68 years old, range of 49–84 years old). CT scans were performed on pts, which showed lung lesions in the RT field. 18F-FDG-PET/CT scans were analyzed qualitatively as negative or positive, and the presence of the lung area with a high 18F-FDG uptake pattern was distinguished as the following: focal/wide, deep/shade, or homogeneous/inhomogeneous. Furthermore, the following semiquantitative parameters were collected: gSUVmax (global standardized uptake value max), MTV (tumor metabolic volume), metabolic spatial distribution (MSD) = proximal SUVmax/distal SUVmax, and intratumoral difference in spatial distribution (IDSD%) = [distal SUVmax/proximal SUVmax] × 100. 18F-FDG PET/CT was related to the pts’ outcome (biopsy and/or clinical–instrumental follow-up): positive for lung relapse, negative if the lesions were phlogistic. The following diagnostic performance parameters of 18F-FDG PET/CT were calculated: sensitivity (Sens), specificity (Spec), diagnostic accuracy (DA), positive predictive value (PPV), and negative predictive value (NPV). Qualitative variables were compared by Chi-squared test, while for semiquantitative parameters Student’s t-test was applied; p < 0.05 was considered statistically significant. Statistics tests were performed with MedCalc V.22.018 ©2024. In 76/94 (80.8%) pts, 18F-FDG uptake was higher compared to the background; in 18/94 (19.2%) no high 18F-FDG uptake areas were detected. Outcome was positive for lung relapse in 49/94 pts, while negative in 45/94, with disease prevalence of 52.13% (95%CI = 41.57–62.54%). In the 18/94 pts without high 18F-FDG uptake, the outcome was negative for lung relapse. In 49/76 pts with higher 18F-FDG uptake, the outcome confirmed the presence of relapse, while in 27/76 the lesion was phlogistic. Results about the Sens, Spec, DA, PPV, and NPV (95%CI) were, respectively: 100% (92.75–100%), 40% (25.7–55.67%), 71.28% (61.02–80.14%), 64.47% (58.84–69.73%), and 100% (81.47–100%). Chi-square test showed significant statistical difference between the positive and negative outcome for patterns focal/wide (p = 0.02) and deep/shade (p < 0.00001). A total of 35/49 (71.4%) pts with lung relapse had a focal lesion and 15/27 (55.6%) with phlogosis had a wide pattern. A total of 34/49 (69.4%) pts with lung relapse had a deep pattern and 25/27 (92.6%) with lung phlogosis had the shade one. Significant difference was observed in evaluating the three patterns (p = 0.00007), with prevalence of “focal/deep/homogeneous” patterns in lung relapse and “wide/shade/inhomogeneous” in phlogosis. gSUVmax, MTV, MSD, and IDSD% were in the following order: in the 76 pts, 5.63 (1.4–24.7), 42.49 (4.94–193), 3.61 (1–5.54), and 70.7% (18–100%); in the 49/76 true positive pts, 6.93 (1.5–24.7), 35.28 (4.94–85.99), 3.30 (1.05–5.54), and (18–95%); in the 27/76 false positive pts, 3.27 (1.4–19.2), 38.37 (4.94–193), 1.57 (1–2.13), and 78.6% (4.7–100%). The difference was statistically significant only for MSD (t = 2.779; p = 0.0069) and IDSD% (t = 2.769; p = 0.0071). 18F-FDG-PET/CT confirms its high sensitivity and NPV in evaluating lung lesions after RT. To improve physician confidence in interpreting lung 18F-FDG uptake without further support, MSD and IDSD% could be considered. Heterogeneity of lung lesions, especially in radiotreated tissue, can be turned from a drawback to a resource and analyzed for differentiating relapses from EBRT side effects. Considering the calculation of semiquantitative parameters that require “human intelligence”, even if slightly more time-consuming, can improve the nuclear physician’s confidence in interpreting 18F-FDG PET/CT images. Full article
(This article belongs to the Section Radiobiology and Nuclear Medicine)
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23 pages, 3553 KB  
Article
Metabolic Profiling, Tissue Distribution, and Tolerance Assessment of Bopu Powder in Laying Hens Following Long-Term Dietary Administration
by Hongting Wang, Xinhao Wang, Jiaxin Xu, Zihui Yang, Zhen Dong, Jianguo Zeng and Hua Liu
Vet. Sci. 2025, 12(9), 848; https://doi.org/10.3390/vetsci12090848 - 2 Sep 2025
Abstract
This study aimed to elucidate the metabolic profile and safety of Bopu Powder in laying hens, focusing on its principal alkaloids protopine (PRO) and allocryptopine (ALL). Nine hens received intravenous PRO (1 mg/kg·bw), ALL (1 mg/kg·bw), or saline. Blood (5–120 min post-dose) and [...] Read more.
This study aimed to elucidate the metabolic profile and safety of Bopu Powder in laying hens, focusing on its principal alkaloids protopine (PRO) and allocryptopine (ALL). Nine hens received intravenous PRO (1 mg/kg·bw), ALL (1 mg/kg·bw), or saline. Blood (5–120 min post-dose) and feces (48 h collection) were analyzed via LC-Q-TOF-MS, revealing 9 ALL and 12 PRO metabolites, including two novel structures. In a separate 56-day trial, 324 hens were assigned to control, 50 mg/kg Bopu Powder (BP), or 500 mg/kg Bopu Powder (BPX) groups. Post-trial analyses showed PRO and ALL residues primarily in their kidneys (BP: PRO 11.21 ng/g, ALL 6.59 ng/g; BPX: PRO 23.62 ng/g, ALL 7.92 ng/g) and livers (BP: PRO 15.52 ng/g; BPX: PRO 269.49 ng/g, ALL 56.14 ng/g). Residues in eggs occurred exclusively in the BPX group (PRO 26.86 ng/g, ALL 12.29 ng/g). No residues were detected in other tissues (jejunum, ileum, ovaries, oviducts, uterus, muscle, fat, gizzard). Serum biochemical indicators and histopathological examinations were used to evaluate the long-term effects of Bopu Powder. The results confirmed that supplementation at doses up to 500 mg/kg did not induce any significant physiological or histopathological alterations. Full article
(This article belongs to the Topic Recent Advances in Veterinary Pharmacology and Toxicology)
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Article
Three-Dimensional Finite Element Comparison of Ballista Spring and Elastic Thread Systems in the Traction of Impacted Maxillary Canines: Implications for Anchorage Control
by Ali Furkan Karakoyunlu, Aysegül Gulec and Ozum Dasdemir Ozkan
Appl. Sci. 2025, 15(17), 9639; https://doi.org/10.3390/app15179639 - 2 Sep 2025
Abstract
Objectives: This study aimed to compare the biomechanical effects of Ballista Spring and Elastic Thread systems on impacted maxillary canines using three-dimensional finite element analysis (FEA). Materials and Methods: Finite element models were constructed from CBCT images of a human maxilla, incorporating cortical [...] Read more.
Objectives: This study aimed to compare the biomechanical effects of Ballista Spring and Elastic Thread systems on impacted maxillary canines using three-dimensional finite element analysis (FEA). Materials and Methods: Finite element models were constructed from CBCT images of a human maxilla, incorporating cortical bone, spongy bone, teeth, and periodontal ligament. Two orthodontic force application methods were simulated: Ballista Spring (0.016-inch stainless steel) and Elastic Thread (0.25 mm medical-grade latex). Both systems delivered a force of 150 g to the impacted canine. Stress distribution and initial displacement patterns were analyzed using ANSYS Workbench. Results: The Ballista Spring generated a more uniform stress distribution across the periodontal ligament and cortical bone, with a maximum von Mises stress of 0.0042 MPa. The impacted canine exhibited an initial displacement of 0.015 μm, primarily in the vertical and distal directions, indicating a controlled movement path. In contrast, the Elastic Thread showed a more concentrated stress pattern with a maximum von Mises stress of 0.0035 MPa, and the impacted canine experienced 0.013 μm of displacement, accompanied by greater lateral deviation and buccal tipping of the adjacent teeth. The Ballista Spring induced higher stress levels on anchorage teeth—particularly the first molars and premolars—while the Elastic Thread exerted more localized stress around the impacted canine and adjacent structures. All observed stress values remained within physiological thresholds, indicating no immediate risk of tissue damage. Conclusions: Both systems were effective in facilitating the eruption of the impacted canines. However, the Ballista Spring provided more favorable stress distribution and controlled displacement, making it suitable for complex cases requiring anchorage preservation. The Elastic Thread, while less biomechanically efficient, remained a practical and cost-effective alternative in patients with adequate periodontal support. Full article
(This article belongs to the Special Issue Biomechanical Analysis in Bioengineering: New Trends and Perspectives)
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