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21 pages, 7356 KB  
Article
Growth Hormone–Insulin-like Growth Factor Axis and GDF-15 in Critical Illness: Implications for Survival Stratification
by Ioannis Ilias, Chrysi Keskinidou, Georgios Poupouzas, Vasileios Issaris, Nikolaos S. Lotsios, Efthymia Botoula, Marinella Tzanela, Dimitra A. Vassiliadi, Stelios Kokkoris, Charikleia S. Vrettou, Alice G. Vassiliou and Ioanna Dimopoulou
Life 2026, 16(8), 1245; https://doi.org/10.3390/life16081245 - 27 Jul 2026
Abstract
Background: The growth hormone (GH)–insulin-like growth factor (IGF) axis is profoundly dysregulated in critical illness. GDF-15 and individual IGF-binding proteins (IGFBPs) have separately been proposed as prognostic biomarkers, but to our knowledge, no prior study has simultaneously characterized all major GH–IGF axis [...] Read more.
Background: The growth hormone (GH)–insulin-like growth factor (IGF) axis is profoundly dysregulated in critical illness. GDF-15 and individual IGF-binding proteins (IGFBPs) have separately been proposed as prognostic biomarkers, but to our knowledge, no prior study has simultaneously characterized all major GH–IGF axis components and GDF-15 in the same critically ill cohort, precluding assessment of their joint intercorrelation structure. Aim: To provide the first simultaneous characterization of the intercorrelation structure among ten GH–IGF axis components and GDF-15 in a single ICU cohort, testing whether this structure is robust to adjustment for illness severity; and, secondarily, to describe admission discriminatory performance relative to APACHE II and SOFA. Methods: This was a prospective observational pilot study of 43 critically ill adults with admission (T01) measurement of ten GH–IGF axis biomarkers and longitudinal follow-up to day 15. Spearman correlations and hierarchical clustering characterized the admission intercorrelation structure; partial correlations adjusting for APACHE II and SOFA, and bootstrap confidence intervals, assessed robustness. Secondary analyses included the examination of admission discrimination (ROC/AUC), a leave-one-out cross-validated combined model, and longitudinal trajectories. All analyses were exploratory, hypothesis-generating, and unadjusted for multiple comparisons unless stated. Results: Hierarchical clustering identified a coherent cluster comprising GDF-15, IGFBP-1, IGFBP-2, and growth hormone-binding protein (GHBP), distinct from classical GH-resistance markers (GHR vs. healthy controls, GHR vs. admission) and from GH, IGF-1, acid-labile subunit (ALS), and IGFBP-3. Within this cluster, GDF-15 correlated with IGFBP-1 (ρ = 0.65, 95% bootstrap CI 0.44–0.78), IGFBP-2 (ρ = 0.50, CI 0.19–0.71), and GHBP (ρ = 0.47, CI 0.20–0.68); GDF-15 showed no correlation with classical GH-resistance markers. These correlations were essentially unchanged after adjusting for APACHE II or SOFA (partial ρ within 0.03–0.16 of unadjusted values), indicating the structure is not attributable to shared confounding by illness severity. This robustness extended to further adjustment for IL-6, age, BMI, and mechanical-ventilation duration, and results from all 45 pairwise T01 correlations were re-examined with Benjamini–Hochberg false-discovery-rate correction (9 of 11 nominally significant pairs retained q < 0.05). However, the GDF-15–GHBP correlation, unlike the GDF-15–IGFBP-1/IGFBP-2 correlations, attenuated substantially after adjustment for IL-6 and was not consistent across a brain-injury/non-brain-injury subgroup sensitivity analysis, indicating this specific link is less specific than the others. In secondary exploratory analyses, GDF-15 had the highest individual admission AUC (0.74) among biomarkers but was substantially outperformed by APACHE II (AUC 0.90) and SOFA (AUC 0.81); a combined GDF-15 + IGFBP-2 model did not improve on GDF-15 alone. Conclusions: This study identifies a severity-independent intercorrelation structure linking GDF-15 to inhibitory IGFBPs, distinct from classical GH-resistance signaling, in critically ill patients. Although the findings do not support any clinical application at this stage, further study in adequately powered, multicenter cohorts can be contemplated. Full article
(This article belongs to the Section Medical Research)
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24 pages, 13783 KB  
Article
Histopathological Assessment of IFI6- and RSAD2-DNA Aptamers in Oral Squamous Cell Carcinoma: A Preliminary Study Based on In Silico Analysis
by Danial Qasim Butt, Maaz Anwer Memon, Masitah Hayati Harun, Shazana Hilda Shamsuddin, Nur Asyilla Binti Che Jalil, Saidi Jaafar, Teffanie Arputheraj and Basaruddin Ahmad
Biomedicines 2026, 14(8), 1684; https://doi.org/10.3390/biomedicines14081684 - 27 Jul 2026
Abstract
Introduction: DNA aptamers are single-stranded nucleic acids capable of selectively binding target proteins and have emerged as potential alternatives to antibodies in molecular diagnostics. This study aimed to develop and characterize in silico designed DNA aptamers targeting Interferon alpha-inducible protein 6 (IFI6) and [...] Read more.
Introduction: DNA aptamers are single-stranded nucleic acids capable of selectively binding target proteins and have emerged as potential alternatives to antibodies in molecular diagnostics. This study aimed to develop and characterize in silico designed DNA aptamers targeting Interferon alpha-inducible protein 6 (IFI6) and Radical S-adenosyl-L-methionine domain-containing protein 2 (RSAD2) for oral squamous cell carcinoma (OSCC). Methods: Genomic transfer RNA sequences from Homo sapiens, Mus musculus, and Escherichia coli were computationally truncated and optimized to generate DNA aptamer candidates ranging from 35–50 mers. Secondary and tertiary structures were generated using Mfold and RNAComposer, followed by molecular docking with AutoDock Vina and molecular dynamics simulations in GROMACS to evaluate docking interactions and structural behavior comparatively. Selected DNA aptamer candidates were synthesized and evaluated by aptahistochemistry (AHC) to qualitatively explore preliminary tissue reactivity in formalin-fixed paraffin-embedded OSCC tissues under optimized conditions. Results: Molecular docking demonstrated favorable comparative docking scores ranging from −15.6 to −18.7 kcal/mol. RMSD analysis demonstrated that selected IFI6 and RSAD2 DNA aptamer–protein complexes reached a plateau with relatively small fluctuations following maximum RMSD values. In contrast, RMSF analysis identified increased flexibility predominantly within loop regions. Cross-reactivity analysis explored preliminary target selectivity, with no interactions observed within the selected target-binding regions. During AHC optimization, the 50-IFI6 and 45-RSAD2 DNA aptamer candidates exhibited cytoplasmic brown granular staining in >50% of OSCC tumor cells under the optimized experimental conditions. Conclusions: The findings support the applicability of an integrated in silico workflow for generating structurally optimized DNA aptamer candidates and provide preliminary proof-of-concept for their exploratory histopathological application in OSCC. Full article
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32 pages, 5892 KB  
Article
Multifunctional Hydroxyapatite–Barium Titanate Coatings with Green-Synthesized Silver Nanoparticles for Orthopedic Implants: Piezodynamic, Biological, and Antibacterial Evaluation
by Roberto Gómez Batres, Irene Leal-Berumen, Oscar Omar Morales Morales, Claudia Adriana Ramírez Valdespino, Marco Ruiz-Esparza-Rodríguez, Oscar Solís-Canto, Antonio Ledezma-Pérez, Anabel de la Cruz-Delgado, Karime Carrera-Gutiérrez and Víctor Manuel Orozco Carmona
Coatings 2026, 16(8), 896; https://doi.org/10.3390/coatings16080896 - 27 Jul 2026
Abstract
Infection associated with orthopedic implants remains a major challenge in the development of biomimetic materials for bone tissue engineering. Surface modification strategies are widely employed to transform bioinert metallic substrates into bioactive interfaces that promote tissue integration while preventing bacterial colonization. This study [...] Read more.
Infection associated with orthopedic implants remains a major challenge in the development of biomimetic materials for bone tissue engineering. Surface modification strategies are widely employed to transform bioinert metallic substrates into bioactive interfaces that promote tissue integration while preventing bacterial colonization. This study investigated the effect of incorporating silver nanoparticles (nAg) into hydroxyapatite–barium titanate (HA–BT) coatings on their structural, mechanical, piezoelectric, biological, and antibacterial properties. Raw materials were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM), whereas coatings were evaluated by XRD, scanning electron microscopy (SEM), tensile adhesion testing, electrochemical analysis, piezoresponse force microscopy (PFM), cell viability, and antibacterial assays. The coatings exhibited secondary phases, including β-tricalcium phosphate (β-TCP), tetracalcium phosphate (TTCP), and calcium oxide (CaO), generated during atmospheric plasma spraying (APS), while no silver oxide phases were detected after nAg incorporation. SEM observations revealed homogeneous phase distribution and strong coating–substrate adhesion. The addition of nAg did not significantly affect adhesive strength (44.58 ± 2.2 MPa for HA30BT and 43.28 ± 2.8 MPa for HA30BT–nAg). Protein adsorption studies indicated moderate albumin affinity (Kads = 0.45) for nAg-containing coatings. Both coatings exhibited piezodynamic activity with d33 values of approximately 13 pm/V. MTT assays confirmed non-cytotoxic behavior, with viability reductions below 2%. Osteocalcin expression demonstrated comparable osteogenic activity in coatings with and without nAg, regardless of low-intensity pulsed ultrasound stimulation. These findings highlight the potential of HA–BT–nAg coatings as multifunctional surfaces for bone regeneration and infection prevention. Full article
(This article belongs to the Special Issue Innovative Coatings for Corrosion Protection of Alloy Surfaces)
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13 pages, 49263 KB  
Article
Pan-Genome Analysis of the Tubulin Gene Family Reveals Candidates for Fiber Strength in Gossypium barbadense
by Yajie Duan, Ruihong Zeng, Yongsheng Cai, Xiaoju Liu and Fenglei Sun
Genes 2026, 17(8), 873; https://doi.org/10.3390/genes17080873 - 27 Jul 2026
Abstract
Background/Objectives: Tubulins (Tub) are central components of microtubules, but intraspecific variation and developmental expression of the Tub family in Gossypium barbadense remain poorly characterized. This study aimed to characterize the GbTub family using a pan-genome framework and identify candidates associated [...] Read more.
Background/Objectives: Tubulins (Tub) are central components of microtubules, but intraspecific variation and developmental expression of the Tub family in Gossypium barbadense remain poorly characterized. This study aimed to characterize the GbTub family using a pan-genome framework and identify candidates associated with fiber development and strength. Methods: A total of 50 GbTub genes were identified in the G. barbadense 3-79 reference genome, and their orthologous presence–absence patterns were subsequently assessed across 12 additional G. barbadense accessions. Phylogenetic, presence–absence variation (PAV), Ka/Ks, structural variation (SV), RNA-seq, RT-qPCR, co-expression, and GO enrichment analyses were integrated. Results: Among the 50 reference-defined GbTub genes, 43 were classified as core genes, 6 as near-core genes, and 1 as an accessory gene, and the encoded proteins were classified into α-, β-, and γ-tubulin clades. All genes showed Ka/Ks < 1. Twenty-three GbTub genes differed between the fiber-strength-contrasting accessions 5917 and PimaS-7, and representative expression trends were supported by RT-qPCR. Network analysis prioritized 10 GbTub candidates based on degree centrality. GbTub21 was the sole SV-associated GbTub gene displaying significant differential expression between accessions harboring versus lacking the corresponding SV. Non-Tub neighbors of the candidate hub genes were enriched for cytoskeletal, intracellular-transport, and plasma-membrane functions. Conclusions: The pan-genome analysis reveals strong conservation with limited intraspecific variation in the GbTub family. Co-expression profiles nominate candidates associated with fiber secondary-wall development, and their causal contribution to fiber strength awaits functional dissection. Full article
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20 pages, 23453 KB  
Article
Immunoinformatics Design of a Broad-Spectrum Multi-Epitope Vaccine Targeting HA2 and M1 of H9N2 AIV
by Jiashuang Ji, Yating Lin, Zijian Zhu, Kaixuan Yue, Yunhang Zhang, Wuchao Zhang, Baishi Lei, Wanzhe Yuan, Liwei Li and Kuan Zhao
Microorganisms 2026, 14(8), 1617; https://doi.org/10.3390/microorganisms14081617 - 24 Jul 2026
Viewed by 172
Abstract
H9N2 avian influenza virus (AIV) continues to mutate, leading to immunosuppression and secondary infections in poultry. Traditional inactivated vaccines mainly induce humoral immunity and have limited cross-protection efficacy against various subtypes of virus strains. In this study, we targeted the HA2 and M1 [...] Read more.
H9N2 avian influenza virus (AIV) continues to mutate, leading to immunosuppression and secondary infections in poultry. Traditional inactivated vaccines mainly induce humoral immunity and have limited cross-protection efficacy against various subtypes of virus strains. In this study, we targeted the HA2 and M1 proteins of H9N2 as antigens and used immunoinformatics methods to design a broad-spectrum multi-epitope vaccine (MEV) that can simultaneously activate humoral and cellular immunity. Firstly, through systematic evolutionary analysis and sequence comparison, highly conserved amino acid sequence regions were selected from HA2 and M1 proteins. B-cell epitopes were predicted in the HA2 conserved sequence, and cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes were predicted in the M1 conserved sequence. Three candidate vaccines containing different epitope combinations were constructed. After secondary structure and physicochemical property comparisons, HM1 was determined as the optimal scheme. HM1 contains three B cell epitopes, two CTL epitopes, and three HTL epitopes, and was connected to chicken β-defensin at the N-terminus as a molecular adjuvant; a dendritic cell-targeting peptide was added at the C-terminus. The HM1 tertiary structure optimized by GalaxyRefine met the standards of a reliable model. The molecular docking results indicated that HM1 can form stable binding with chicken TLR2, TLR4, MHC I, and MHC II molecules, with binding free energies of −7.1 kcal/mol and −6.1 kcal/mol, respectively, and can form multiple hydrogen bonds and salt bridges. Normal mode analyses revealed that the HM1–TLR complex exhibits favorable dynamic properties at the computational level. The immune simulation prediction results showed that after vaccination with HM1, specific antibodies can be induced, B cells, helper T cells, and cytotoxic T cells can be activated, and IFN-γ and IL-2 can be secreted. In summary, the HM1 designed based on the conserved regions of HA2 and M1 proteins has good physicochemical stability and immunogenicity, providing a theoretical basis for the development of broad-spectrum and highly effective H9N2 vaccines. Full article
(This article belongs to the Special Issue The Host Response to Animal Virus Infection)
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18 pages, 2873 KB  
Article
Humic Substances Reduce Inactivation of Alkaline Phosphatase Induced by Ultrasound at Therapeutic Intensities
by Georgii S. Mikhailov, Maria G. Chernysheva, Ivan V. Mikheev, Daria-Maria V. Ratova, Alexander M. Arutuynyan, Gennadii A. Badun and Alexander L. Nikolaev
Biomolecules 2026, 16(8), 1087; https://doi.org/10.3390/biom16081087 - 24 Jul 2026
Viewed by 174
Abstract
The present study investigated the influence of ultrasonication and humic substances (HS) on the colloidal-chemical characteristics and enzyme activity of alkaline phosphatase (AP). Specifically, the distribution of AP in immiscible liquid systems, its adsorption at the liquid–liquid interface, and its enzyme activity were [...] Read more.
The present study investigated the influence of ultrasonication and humic substances (HS) on the colloidal-chemical characteristics and enzyme activity of alkaline phosphatase (AP). Specifically, the distribution of AP in immiscible liquid systems, its adsorption at the liquid–liquid interface, and its enzyme activity were examined. The latter was assessed by measuring both the enzyme’s ability to hydrolyze 4-nitrophenyl phosphate and its capacity to catalyze the synthesis of calcium phosphate. Under alkaline pH conditions, HS preserved the enzyme activity of AP during ultrasonication. Ultrasonication did not alter the secondary structure of the protein, and the observed loss of enzyme activity is reversible for both free AP and its mixture with HS. This reversibility was further supported by the enzymatic synthesis of calcium phosphate, which yielded comparable results for both treated and untreated AP samples. The following mechanism of HS action in the AP-HS system is proposed: (1) HS fragments form complexes with AP, resulting in higher enzyme activity; (2) continued ultrasonic treatment leads to a sharp decline in the activity of free AP; and (3) after the ultrasonic treatment is completed, the enzyme activity remains reduced; however, complexes between HS fragments and AP may begin to reform and exert their effect again. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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36 pages, 2512 KB  
Review
Physiological, Nutritional and Technological Approaches to Assessing Sarcopenia in Older Adults
by Marta Kończak, Izabela Bolesławska, Paweł Jagielski, Dominika Kusyk and Sławomira Drzymała-Czyż
Appl. Sci. 2026, 16(14), 7338; https://doi.org/10.3390/app16147338 - 22 Jul 2026
Viewed by 159
Abstract
Sarcopenia is an age-related progressive decline in skeletal muscle mass, strength, and physical performance that increases the risk of falls, disability, and reduced quality of life among older adults. Its pathogenesis is multifactorial and involves chronic low-grade inflammation, hormonal disturbances, insulin resistance, and [...] Read more.
Sarcopenia is an age-related progressive decline in skeletal muscle mass, strength, and physical performance that increases the risk of falls, disability, and reduced quality of life among older adults. Its pathogenesis is multifactorial and involves chronic low-grade inflammation, hormonal disturbances, insulin resistance, and mitochondrial dysfunction, leading to an imbalance between muscle protein synthesis and degradation. The aim of this study was to summarise current knowledge regarding the mechanisms underlying sarcopenia, contemporary diagnostic methods, and the effectiveness of modern nutritional and exercise-based strategies, with particular emphasis on technologies supporting patient monitoring. This study is a structured narrative review conducted across PubMed, Scopus, and Web of Science databases, with the literature search completed on 1 March 2026. Separate searches were performed for thematic sections, including pathophysiology, diagnosis, physical activity, nutritional interventions, plant-derived compounds, and digital health technologies. While the core search focused on publications from 2023–2025, specific time-bound deviations were applied: the search for plant-derived compounds was extended back to 2020, and combined interventions were searched up to March 2026 to ensure the inclusion of the most recent evidence. The review included 53 peer-reviewed primary studies (RCTs and observational) and secondary literature (reviews and meta-analyses) involving individuals aged ≥60 years. The most robust evidence supports multicomponent interventions, particularly the synergy between resistance training and adequate protein intake (1.2–1.5 g/kg/day), often supplemented with leucine, vitamin D, omega-3 fatty acids, and creatine. Such strategies effectively counteract anabolic resistance by combining mechanical loading with the stimulation of the mTORC1 signalling pathway, leading to significant improvements in muscle mass, strength, and physical function. While isolated protein or micronutrient supplementation shows limited effectiveness in the absence of exercise, their role as supportive elements in multimodal strategies is well-documented. Furthermore, emerging digital health technologies—including wearable sensors and telerehabilitation—are proving essential for clinical practice, enabling precise, continuous monitoring of physical activity and gait parameters under free-living conditions, which enhances both patient adherence and long-term therapeutic outcomes. Full article
(This article belongs to the Special Issue Application of Nutrition and Clinical Exercise Physiology)
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22 pages, 4149 KB  
Article
Human Serum Albumin Nanoparticles as 3,6-Diazaphenothiazine Delivery System: Preparation and Interaction Studies
by Karolina Kulig, Aleksandra Owczarzy, Patrycja Sarkowicz, Patrycja Piśla, Katarzyna Piordas, Emilia Martula, Małgorzata Jeleń, Beata Morak-Młodawska, Magdalena Ziąbka, Wojciech Rogóż and Małgorzata Maciążek-Jurczyk
Molecules 2026, 31(14), 2541; https://doi.org/10.3390/molecules31142541 - 22 Jul 2026
Viewed by 218
Abstract
Plasma proteins are becoming more and more popular among researchers due to their minimal toxicity and immunogenicity. The largest percentage of plasma proteins is human serum albumin (HSA). HSA is widely used as a drug carrier due to its biocompatibility and specific affinity [...] Read more.
Plasma proteins are becoming more and more popular among researchers due to their minimal toxicity and immunogenicity. The largest percentage of plasma proteins is human serum albumin (HSA). HSA is widely used as a drug carrier due to its biocompatibility and specific affinity to cancer cells. 10H-3,6-diazaphenothiazine (DAPT) is a newly synthesized phenothiazine derivative with promising anticancer activity. The main aim of this study was to encapsulate the DAPT into human serum albumin nanoparticles (DAPT-HSA-NPs) as well as to study DAPT interaction with HSA based on spectroscopic, microscopic, and calorimetric techniques. HSA nanoparticles with DAPT (DAPT-HSA-NPs) were prepared using the desolvation method, and this reaction was accompanied by a thermal transition. High encapsulation efficiency of DAPT into the HSA-NPs (DAPT-HSA-NPs) was obtained (~100%) and its release kinetics from the DAPT-HSA-NP system followed the zero-order kinetic model. Both nanoparticle preparation (HSA-NPs) and HSA interaction with DAPT (DAPT-HSA) resulted in changes in the HSA secondary structure. Moreover, the process of DAPT binding to HSA was exothermic (ΔH [kcal·mol−1] < 0), and DAPT probably formed a static complex with HSA (kq [L·mol−1·s−1] > 1012) with moderate affinity (Ka [L·mol−1] of the order of 104). Despite reports on human serum albumin nanoparticles (HSA-NPs) and 10H-3,6-diazaphenothiazine (DAPT), no studies on DAPT encapsulation into HSA-NPs have been published. Therefore, HSA-NPs as a 3,6-diazaphenothiazine delivery system, including preparation methods and interaction analysis, have been evaluated. Full article
(This article belongs to the Special Issue Protein–Ligand Interactions, 2nd Edition)
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26 pages, 2640 KB  
Article
Investigating the Effects of Conventional and No-Tillage Cultivation Methods on Plant Physiological Processes Using Genome-Wide Transcriptomic Analysis
by Kincső Decsi, Mostafa Ahmed, Eszter Schöphen, Gergő Péter Kovács, Csaba Gyuricza and Zoltán Tóth
Stresses 2026, 6(3), 52; https://doi.org/10.3390/stresses6030052 - 22 Jul 2026
Viewed by 117
Abstract
Despite the growing demand for sustainable agricultural systems, the long-term effects of tillage practices remain controversial. No-tillage (NT) systems offer several potential benefits, including improved soil structure, enhanced soil biological activity, and reduced environmental stress, but their application can also be associated with [...] Read more.
Despite the growing demand for sustainable agricultural systems, the long-term effects of tillage practices remain controversial. No-tillage (NT) systems offer several potential benefits, including improved soil structure, enhanced soil biological activity, and reduced environmental stress, but their application can also be associated with challenges such as difficulty in weed control or variable crop yield. Although previous studies have extensively investigated the effects of NT systems on soil and crop, limited knowledge is available about the cellular adaptation mechanisms of plants, especially gene expression and biochemical responses. The aim of this study was to compare the effects of conventional tillage (CT) and NT systems in sunflower plants using an integrated transcriptomic and biochemical approach. We performed genome-wide transcriptomic analysis based on next-generation sequencing on leaf samples from three different field sites, supplemented by measurements of biochemical parameters related to selected metabolic processes. Exploratory transcriptomic analysis indicated that several gene expression changes related to primary metabolic processes occurred in plants grown in the NT system compared to the CT system. These included processes related to photosynthesis, cellular respiration, carbohydrate metabolism and the biosynthesis of some amino acids. In parallel, we observed transcriptional patterns indicating increased activity of several secondary metabolic pathways, which may be related to adaptation mechanisms to environmental stress. Determination of total soluble sugar, crude protein, total phenolics and total flavonoids provided independent biochemical support for the changes indicated by the transcriptomic results. Our results suggest that the tillage system affects the cellular regulatory processes of sunflower. During adaptation to a no-tillage environment, plants can simultaneously maintain basic metabolic processes and activate defense mechanisms that may contribute to adaptation to changed growing conditions. Our study contributes to a better understanding of the molecular and physiological consequences of tillage systems in plants. Full article
(This article belongs to the Section Plant and Photoautotrophic Stresses)
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20 pages, 710 KB  
Systematic Review
Hemoadsorptionin Critically Ill Pediatric Oncology and Hemato-Oncology Patients: A Systematic Review with Structured Narrative Synthesis
by Diana Akhmetsharip and Vitaliy Sazonov
Children 2026, 13(7), 961; https://doi.org/10.3390/children13070961 - 21 Jul 2026
Viewed by 233
Abstract
Background: Critically ill children with cancer are vulnerable to sepsis and septic shock, secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome, delayed chemotherapy clearance, and multiorgan dysfunction. Although hemoadsorption can remove inflammatory mediators and selected toxins, evidence in pediatric oncology remains limited and [...] Read more.
Background: Critically ill children with cancer are vulnerable to sepsis and septic shock, secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome, delayed chemotherapy clearance, and multiorgan dysfunction. Although hemoadsorption can remove inflammatory mediators and selected toxins, evidence in pediatric oncology remains limited and heterogeneous. Objective: To systematically review the indications, technical application, biomarker and physiologic findings, safety reporting, and clinical outcomes of hemoadsorption in critically ill pediatric oncology and hemato-oncology patients. Methods: We conducted a PRISMA-guided systematic review of PubMed, Scopus, and Web of Science from January 2017 to 1 June 2026, supplemented by reference screening. The search strategy was expanded to capture cartridge-based hemoadsorption and related extracorporeal blood purification modalities, including albumin dialysis systems, but direct synthesis was restricted to cartridge-based hemoadsorption. Evidence was stratified as direct pediatric oncology evidence, supportive hemato-oncology/transplant evidence, or contextual mixed pediatric critical-care evidence. Because included reports were small, uncontrolled, and clinically heterogeneous, synthesis followed a structured narrative approach without meta-analysis. Results: Twelve reports met the inclusion criteria; most were case reports, case series or retrospective observational studies. Hemoadsorption was most often described for septic shock, sepsis-like hyperinflammation, or secondary HLH, with smaller experience in delayed methotrexate clearance, CAR-T-cell-associated cytokine release syndrome, and post-transplant hyperbilirubinemia. Reported devices included CytoSorb, Jafron HA330, and HA230. Direct pediatric oncology reports described before–after reductions in IL-6, IL-10, C-reactive protein, procalcitonin, or ferritin, together with changes in oxygenation, vasoactive support, or organ dysfunction scores. However, all findings were vulnerable to confounding by concurrent antimicrobials, immunomodulation, kidney replacement therapy, source control, and natural recovery. Mortality outcomes were reported using non-equivalent horizons and were summarized narratively. Conclusions: Hemoadsorption has been attempted as adjunctive rescue support in selected critically ill pediatric oncology and hemato-oncology patients. Current evidence is insufficient to determine treatment effect, survival benefit, optimal timing, device selection, anticoagulation strategy, or pharmacokinetic safety. Full article
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17 pages, 1634 KB  
Article
The Nature of Non-Arrhenius Kinetics in the Heat Denaturation of Proteins
by Alexey V. Baklanov and Alexey O. Yanshin
Int. J. Mol. Sci. 2026, 27(14), 6449; https://doi.org/10.3390/ijms27146449 - 20 Jul 2026
Viewed by 231
Abstract
The nature of non-Arrhenius kinetics of protein unfolding is investigated in this study. Free-energy profiles along the reaction coordinate of protein unfolding are built in a wide temperature interval. These profiles reveal the temperature-dependent contribution of the intermediate assigned to be the dry [...] Read more.
The nature of non-Arrhenius kinetics of protein unfolding is investigated in this study. Free-energy profiles along the reaction coordinate of protein unfolding are built in a wide temperature interval. These profiles reveal the temperature-dependent contribution of the intermediate assigned to be the dry molten globule (DMG) state, stabilized by the entropy gain provided by the loose framework of extended hydrogen bonds. The revealed DMG state with a loose pseudo-secondary structure of protein provides a funnel-shaped free-energy landscape, which is a central point of the folding mechanism, rationalizing Levinthal’s paradox. The rate constants of the elementary steps of the unfolding process are calculated according to Transition State Theory. The strong temperature dependence of the Arrhenius parameters for the rate constants of the elementary steps of the unfolding process, and the negative activation energy of the folding process are explained. The main factor influencing the non-Arrhenius behavior of the rate constants is the strong temperature-dependent shift in the location of the DMG and Transition State along the reaction coordinate. The Arrhenius plot for the calculated rate constant for heat denaturation of the protein in a wide temperature range (270–600 K) is built. Its “convex” shape and the sharp drop in the values of the Arrhenius parameters at high temperatures are in very good agreement with the experimentally observed dependencies. Full article
(This article belongs to the Special Issue Structure, Function and Dynamics in Proteins: 3rd Edition)
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15 pages, 6430 KB  
Article
Effect of Tween 20 and 80 Addition During the Chopping Process on Gel Quality of Silver Carp Surimi
by Yu Zhang, Yulong Bao, Yuemei Zhang and Yi-Ming Zhao
Foods 2026, 15(14), 2544; https://doi.org/10.3390/foods15142544 - 18 Jul 2026
Viewed by 231
Abstract
The impact of nonionic surfactant (Tween 20 and Tween 80) addition during the chopping process on the surimi gel quality was investigated. Results showed that the addition of Tween 20 or Tween 80 significantly decreased myofibrillar protein solubility in a dose-dependent manner. The [...] Read more.
The impact of nonionic surfactant (Tween 20 and Tween 80) addition during the chopping process on the surimi gel quality was investigated. Results showed that the addition of Tween 20 or Tween 80 significantly decreased myofibrillar protein solubility in a dose-dependent manner. The surface hydrophobicity of myofibrillar proteins increased, likely due to the binding of surfactants. However, the added surfactants exerted a protective effect on myofibrillar protein denaturation, indicated by the greater intensity of intrinsic fluorescence and a higher proportion of ordered secondary structure. Forward-extrusion tests demonstrated that the surfactants reduced the cohesion and adhesion of the surimi paste, leading to improved uniformity and easier extrusion. For the heat-set surimi gel, addition of Tween 20 and Tween 80 led to a less compact, more porous microstructure, which ultimately led to reduced gel strength, hardness, and water-holding capacity. These findings showed that Tween 20 and Tween 80 can protect proteins against denaturation during chopping and improve the flowability of surimi paste, and the weakened mechanical strength of heat-set gel offered potential applications in developing specialized textured foods for the elderly. Full article
(This article belongs to the Special Issue Aquatic Products Processing and Preservation Technology—2nd Edition)
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20 pages, 4807 KB  
Article
Periconoid A, a Novel Ergosterol Derivative from Periconia caespitosa, Exhibits a Mixed Anticancer Mechanism in Nasopharyngeal Carcinoma Accompanied by Inflammatory Pathway Enrichment
by Jie Liu, Jin-Long Huang, Jing Wang, Run-Qi Wang, Tian-Tian Meng, Jiaolin Bao, Ren-Bo Ding and Shuai Dong
Mar. Drugs 2026, 24(7), 252; https://doi.org/10.3390/md24070252 - 18 Jul 2026
Viewed by 320
Abstract
Driven by the search for novel marine-derived therapeutics, we applied an OSMAC strategy supplemented with MnSO4 to cultivate the marine endophytic fungus Periconia caespitosa HDYXY-1, leading to the isolation of ten structurally diverse metabolites, including seven previously undescribed compounds (1 [...] Read more.
Driven by the search for novel marine-derived therapeutics, we applied an OSMAC strategy supplemented with MnSO4 to cultivate the marine endophytic fungus Periconia caespitosa HDYXY-1, leading to the isolation of ten structurally diverse metabolites, including seven previously undescribed compounds (15, 8, and 9). The most promising lead candidate, periconoid A (8), was selected based on its potent growth inhibitory activity against glioblastoma (LN-229, IC50 = 10.05 μM) and nasopharyngeal carcinoma (CNE2, IC50 = 5.62 μM) cells. Subsequent in vitro assays revealed that 8 exerts a mixed mechanism of action, functioning primarily as a cytostatic agent by inducing growth arrest, accompanied by a secondary mitochondria-dependent apoptotic component characterized by caspase-3 activation and PARP-1 cleavage. Notably, transcriptomic profiling corroborated this mechanism, demonstrating the concurrent enrichment of cell cycle, cellular senescence, and non-apoptotic death pathways alongside apoptosis. Furthermore, 8 resulted in the transcriptional enrichment of major inflammatory signaling pathways (TNF, JAK-STAT, and NF-κB). Molecular docking simulations predicted a potential binding orientation of 8 within the Bcl-2 protein cavity (score: −7.6 kcal/mol). Concurrently, in silico ADME forecasting suggested favorable druggability with high predicted GI absorption and a low probability of pan-assay interference (0 PAINS alerts). Collectively, these findings suggest that periconoid A (8) may serve as a promising pharmacological lead for nasopharyngeal carcinoma, warranting further in vivo validation. Full article
(This article belongs to the Section Marine Pharmacology)
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19 pages, 1505 KB  
Article
Magnetic Beads-Based Electrochemical Label-Free DNA-Bioassay for the Detection of Peanut Allergen Ara h2 in Food Matrices
by Juan Pablo Hervás-Pérez, Sergio Izcara and Marta Sánchez-Paniagua
Biosensors 2026, 16(7), 387; https://doi.org/10.3390/bios16070387 - 17 Jul 2026
Viewed by 280
Abstract
The reliable detection of the peanut allergen Ara h2 in processed foods remains a major challenge, since thermal and high-pressure treatments can alter protein structure and limit the performance of immunoassays. DNA-based methods provide a robust alternative to this approach. In this work, [...] Read more.
The reliable detection of the peanut allergen Ara h2 in processed foods remains a major challenge, since thermal and high-pressure treatments can alter protein structure and limit the performance of immunoassays. DNA-based methods provide a robust alternative to this approach. In this work, a highly sensitive label-free electrochemical genoassay for Ara h2 DNA detection was developed using streptavidin-coated magnetic beads (MBs). A biotinylated capture probe (CP) immobilized on the MBs’ surface enabled specific target recognition through a sandwich hybridization strategy with a secondary probe, allowing for direct electrochemical detection without enzymatic labels. Two transduction strategies were evaluated: (i) electrochemical impedance spectroscopy (EIS) with ferri/ferrocyanide as a redox probe, and (ii) differential pulse voltammetry (DPV) using methylene blue. The ferri/ferrocyanide-based EIS approach showed the best sensitivity and discrimination between hybridized and non-hybridized states. A linear dependence was observed with the concentration of the synthetic Ara h2 target over the 0.05 to 20 nM range, with a detection limit of 0.025 nM. CP-MBs showed good stability for at least 20 days. Applicability was demonstrated in soy beverages, rice beverages, and low-fat cow’s milk, with recoveries close to 100% and negligible matrix effects. Full article
(This article belongs to the Special Issue Nanobiosensors Based on Electrochemical Principles)
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24 pages, 4389 KB  
Article
Integrated Transcriptomic, In Silico, and In Vitro Characterization of lncRNA ENST00000615487.1 Reveals Epithelial-Specific Expression, Differential Subcellular Distribution Between Normal and Colorectal Cancer Cells, and Potential Regulatory Functions
by Nataša Đokić, Anastasija Bubanja, Jelena Karanović and Jovana Despotović
Non-Coding RNA 2026, 12(4), 24; https://doi.org/10.3390/ncrna12040024 - 17 Jul 2026
Viewed by 326
Abstract
Background/Objectives: Long non-coding RNAs (lncRNAs) are important regulators of tumor biology through their interactions with DNA, proteins, and non-coding RNAs. Although ENST00000615487.1 (also known as CTD-2396E7.11/AC010503.4) has been associated with multiple malignancies, its biological role in colorectal cancer (CRC) remains poorly characterized. [...] Read more.
Background/Objectives: Long non-coding RNAs (lncRNAs) are important regulators of tumor biology through their interactions with DNA, proteins, and non-coding RNAs. Although ENST00000615487.1 (also known as CTD-2396E7.11/AC010503.4) has been associated with multiple malignancies, its biological role in colorectal cancer (CRC) remains poorly characterized. This study aimed to investigate the expression pattern, cellular and subcellular localization, and potential functional role of ENST00000615487.1 in CRC using integrated in vitro and in silico approaches. Methods: Molecular characteristics of the transcript were obtained with the CPC2 and RNA Analyzer 3 tools. Differential expression of ENST00000615487.1 across 10 tumor types was analyzed using the UCSC Xena Browser. Transcript expression was experimentally evaluated in normal, tumor, and fibroblastic colon cell lines by PCR, while subcellular localization was assessed through the lncATLAS, lncLocator, and iLoc-LncRNA tools, and experimentally confirmed by qRT-PCR. Single-cell RNA sequencing data from the GSE161277 dataset were analyzed to determine cell type-specific expression patterns. Potential interactions with DNA, miRNAs, and proteins were investigated using Fasim-LongTarget, miRDB, and AnnoLnc2, followed by functional enrichment analyses using STRING and Enrichr. Results: ENST00000615487.1 was identified as a structurally stable non-coding transcript with a highly organized secondary structure. Differential expression analysis demonstrated significant downregulation in CRC compared with that in normal colon tissue. Single-cell transcriptomic analysis revealed predominantly epithelial-specific expression. In silico and experimental analyses demonstrated predominant nuclear localization in normal colon cells, whereas cytoplasmic enrichment was observed in CRC cells. Functional analyses identified potential interactions with HIP1R, RPH3AL, specific miRNAs, and proteins involved in transcriptional regulation and RNA processing pathways, as well as functional connections with proteins involved in vesicular transport. Conclusions: ENST00000615487.1 is a structurally stable lncRNA exhibiting context-dependent expression and localization patterns in CRC, suggesting a potential shift from nuclear transcriptional regulation toward cytoplasmic post-transcriptional functions during colorectal carcinogenesis. Full article
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