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25 pages, 1369 KiB  
Article
From Transformers to Voting Ensembles for Interpretable Sentiment Classification: A Comprehensive Comparison
by Konstantinos Kyritsis, Charalampos M. Liapis, Isidoros Perikos, Michael Paraskevas and Vaggelis Kapoulas
Computers 2025, 14(5), 167; https://doi.org/10.3390/computers14050167 - 29 Apr 2025
Viewed by 124
Abstract
This study conducts an in-depth investigation of the performance of six transformer models using 12 different datasets—10 with three classes and two with two classes—on sentiment classification. We use these six models and generate all combinations of triple schema ensembles, Majority and Soft [...] Read more.
This study conducts an in-depth investigation of the performance of six transformer models using 12 different datasets—10 with three classes and two with two classes—on sentiment classification. We use these six models and generate all combinations of triple schema ensembles, Majority and Soft vote. In total, we compare 46 classifiers on each dataset and see in one case up to a 7.6% increase in accuracy on a dataset with three classes from an ensemble scheme and, in a second case, up to 8.5% increase in accuracy on a dataset with two classes. Our study contributes to the field of natural language processing by exploring the reasons for the predominance, in this particular task, of Majority vote over Soft vote. The conclusions are drawn after a thorough investigation of the classifiers that are co-compared with each other through reliability charts, analyses of the confidence the models have in their predictions and their metrics, concluding with statistical analyses using the Friedman test and the Nemenyi post-hoc test with useful conclusions. Full article
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24 pages, 3715 KiB  
Article
Placental Protein Citrullination Signatures Are Modified in Early- and Late-Onset Fetal Growth Restriction
by Owen R. Vaughan, Kasia Maksym, Sara Hillman, Rebecca N. Spencer, Mariya Hristova, Anna L. David and Sigrun Lange
Int. J. Mol. Sci. 2025, 26(9), 4247; https://doi.org/10.3390/ijms26094247 - 29 Apr 2025
Viewed by 214
Abstract
Fetal growth restriction (FGR) is an obstetric condition most frequently caused by placental dysfunction. It is a major cause of perinatal morbidity with limited treatment options, so identifying the underpinning mechanisms is important. Peptidylarginine deiminases (PADs) are calcium-activated enzymes that mediate post-translational citrullination [...] Read more.
Fetal growth restriction (FGR) is an obstetric condition most frequently caused by placental dysfunction. It is a major cause of perinatal morbidity with limited treatment options, so identifying the underpinning mechanisms is important. Peptidylarginine deiminases (PADs) are calcium-activated enzymes that mediate post-translational citrullination (deimination) of proteins, through conversion of arginine to citrulline. Protein citrullination leads to irreversible changes in protein structure and function and is implicated in many pathobiological processes. Whether placental protein citrullination occurs in FGR is poorly understood. We assessed protein citrullination and PAD isozyme abundance (PAD1, 2, 3, 4 and 6) in human placental samples from pregnancies complicated by early- and late-onset FGR, compared to appropriate-for-gestational-age (AGA) controls. Proteomic mass spectrometry demonstrated that the placental citrullinome profile changed in both early- and late-onset FGR, with 112 and 345 uniquely citrullinated proteins identified in early- and late-onset samples, respectively. Forty-four proteins were citrullinated only in control AGA placentas. The proteins that were uniquely citrullinated in FGR placentas were enriched for gene ontology (GO) terms related to neurological, developmental, immune and metabolic pathways. A greater number of GO and human phenotype pathways were functionally enriched for citrullinated proteins in late- compared with early-onset FGR. Correspondingly, late-onset but not early-onset FGR was associated with significantly increased placental abundance of PAD2 and citrullinated histone H3, determined by Western blotting. PAD3 was downregulated in early-onset FGR while abundance of PAD 1, 4 and 6 was less altered in FGR. Our findings show that placental protein citrullination is altered in FGR placentas, potentially contributing to the pathobiology of placental dysfunction. Full article
(This article belongs to the Section Molecular Biology)
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12 pages, 2013 KiB  
Article
Effects of Virtually Led Value-Based Preoperative Assessment on Safety, Efficiency, and Patient and Professional Satisfaction
by José Luis Gracia Martínez, Miguel Ángel Morales Coca, Marta del Olmo Rodríguez, Pablo Vigoa, Jorge Martínez Gómez, Jorge Short Apellaniz, Catalina Paredes Coronel, Marco Antonio Villegas García, Juan José Serrano, Javier Arcos, Cristina Caramés Sánchez, Bernadette Pfang and Juan Antonio Álvaro de la Parra
J. Clin. Med. 2025, 14(9), 3093; https://doi.org/10.3390/jcm14093093 - 29 Apr 2025
Viewed by 220
Abstract
Background: The increasing demand for elective surgery makes optimizing preoperative assessment a priority. Value-based healthcare aims to provide the highest value for patients at the lowest possible cost through various mechanisms, including reorganizing care into integrated practice units (IPUs). However, few studies have [...] Read more.
Background: The increasing demand for elective surgery makes optimizing preoperative assessment a priority. Value-based healthcare aims to provide the highest value for patients at the lowest possible cost through various mechanisms, including reorganizing care into integrated practice units (IPUs). However, few studies have analyzed the effectiveness of implementing virtually led IPUs for preoperative assessment. Methods: We performed a retrospective observational cohort study including patients undergoing elective surgery at a teaching hospital in Madrid, Spain from 1 January 2018 to 31 December 2023, analyzing changes in surgical complications, efficiency, and patient satisfaction between the pre-implementation (2018–2019) and post-implementation (2020–2023) periods. Anesthesiologists’ satisfaction with the virtual assessments was described. During the post-implementation period, preoperative assessment was reorganized as a virtually led IPU. At the IPU appointment, preoperative testing and physical (including airway) examinations were performed by a nurse anesthesiologist. The results were uploaded to the electronic health records, and asynchronous virtual anesthesiologist assessment using a store-and-forward approach was performed. Digital patient education was carried out over the Patient Portal mobile application. Results: A total of 40,233 surgical procedures were included, of which 31,259 were from the post-intervention period. During the post-intervention period, no increase in surgical complications was observed, while same-day cancellations decreased from 4.3% to 2.8% of the total procedures (p < 0.001). The overall process time did not increase, despite the rising number of surgical procedures per year. Patient satisfaction improved. The median time to complete anesthesiologist assessment was significantly lower for virtual assessment (4.5 versus 10 min (p < 0.001), signifying estimated time savings of 716 person-hours per year. Anesthesiologists agreed that virtual assessment was more efficient than in-person evaluation, and half of the participants agreed that virtual preoperative care improved their work–life balance and reduced burnout. Conclusions: A digitally enhanced value-based model of preoperative care can improve efficiency and satisfaction metrics, reducing unnecessary costs and potentially improving the quality of care. Full article
(This article belongs to the Special Issue Advances in the Clinical Management of Perioperative Anesthesia)
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24 pages, 10960 KiB  
Article
Bacterial Cellulose-Based Nanocomposites for Wound Healing Applications
by Alexandra-Ionela Dogaru, Ovidiu-Cristian Oprea, Gabriela-Olimpia Isopencu, Adela Banciu, Sorin-Ion Jinga and Cristina Busuioc
Polymers 2025, 17(9), 1225; https://doi.org/10.3390/polym17091225 - 29 Apr 2025
Viewed by 312
Abstract
Bacterial cellulose (BC) is a polysaccharide produced by Gram-positive and Gram-negative bacteria with a strictly aerobic metabolism, having a huge number of significant applications in the biomedical field. This study investigates the development of bacterial cellulose (BC)-based composite systems that incorporate cerium dioxide [...] Read more.
Bacterial cellulose (BC) is a polysaccharide produced by Gram-positive and Gram-negative bacteria with a strictly aerobic metabolism, having a huge number of significant applications in the biomedical field. This study investigates the development of bacterial cellulose (BC)-based composite systems that incorporate cerium dioxide nanoparticles (CeO2 NPs) used as antibacterial agents to enhance wound healing, particularly for burn treatments. The innovation of this study resides in the integration of CeO2 NPs synthesized by using a precipitation method using both chemical and green reducing agents, ammonium hydroxide (NH4OH) and turmeric extract (TE), in BC membranes composed of ultrathin nanofibers interwoven into a three-dimensional network appearing as a hydrogel mass. Characterization by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR) confirmed the effective deposition of this agent onto the BC matrix. Antibacterial activity tests against E. coli and B. subtilis indicated strong inhibition for the composites synthesized following these routes, particularly for the BC-CeO2-TE-OH sample, processed by employing both precipitating agents. Cytotoxicity evaluations showed no inhibition of cell activity. Additionally, loading the composites with dexamethasone endowed them with analgesic release over 4 h, as observed through ultraviolet–visible spectroscopy (UV-Vis), while the FTIR spectra revealed a sustained drug presence post-release. These findings highlight BC-based films as promising candidates for advanced wound care and tissue engineering applications. Full article
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33 pages, 4942 KiB  
Article
Improved Oil/Water Separation by Employing Packed-Bed Filtration of Modified Quartz Particles
by Nthabiseng Ramanamane and Mothibeli Pita
Water 2025, 17(9), 1339; https://doi.org/10.3390/w17091339 - 29 Apr 2025
Viewed by 258
Abstract
This study explores the development and optimization of quartz-based filtration media for industrial oil–water separation, focusing on enhancing surface wettability, minimizing fouling, and improving oil rejection efficiency. High-purity quartz particles (SiO2: 98%, Fe2O3: 0.18%, particle size: 0.8–1.8 [...] Read more.
This study explores the development and optimization of quartz-based filtration media for industrial oil–water separation, focusing on enhancing surface wettability, minimizing fouling, and improving oil rejection efficiency. High-purity quartz particles (SiO2: 98%, Fe2O3: 0.18%, particle size: 0.8–1.8 mm) were evaluated in three configurations: raw, acid-washed, and surface-coated with hydrophilic nanoparticles (Al2O3 and P2O5). The filtration medium was constructed as a packed-bed of quartz particles rather than a continuous sintered membrane, providing a cost-effective and modular structure for separation processes. Comprehensive material characterization was performed using X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive Spectroscopy (EDS). XRD confirmed the crystalline stability of quartz across all treatments, while SEM and EDS revealed enhanced surface morphology and elemental distribution—especially phosphorus and aluminum—in coated samples. Performance testing with synthetic oily wastewater (initial oil concentration: 183,754.8 mg/L) demonstrated that the coated quartz medium achieved superior separation, reducing residual oil concentration to 29.3 mg/L, compared to 1583.7 mg/L and 1859.8 mg/L for washed and raw quartz, respectively. Contact angle analysis confirmed improved hydrophilicity in coated media, which also exhibited lower fouling propensity. Taguchi optimization (conducted via Minitab 21.3) and regression modeling identified surface coating and operational pressure (optimal at 2.5 bar) as the most significant parameters influencing oil rejection. Post-filtration SEM and XRD confirmed structural integrity and coating durability. Additionally, flux recovery above 90% after backwashing indicated strong regeneration capability. These findings validate surface-modified quartz packed beds as robust, scalable, and economically viable alternatives to conventional membranes in oily wastewater treatment. Future research will explore multilayer coatings, long term performance under aggressive conditions, and AI-based prediction models. Full article
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21 pages, 1114 KiB  
Review
The Emerging Role and Mechanism of E2/E3 Hybrid Enzyme UBE2O in Human Diseases
by Qian Cheng, Zuyin Li, Yongjian Li, Lei Chen, Dingbao Chen and Jiye Zhu
Biomedicines 2025, 13(5), 1082; https://doi.org/10.3390/biomedicines13051082 - 29 Apr 2025
Viewed by 135
Abstract
The ubiquitin–proteasome system (UPS) plays a pivotal role in determining protein fate, regulating signal transduction, and maintaining cellular homeostasis. Protein ubiquitination, a key post-translational modification, is orchestrated by the sequential actions of three primary enzymes, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin [...] Read more.
The ubiquitin–proteasome system (UPS) plays a pivotal role in determining protein fate, regulating signal transduction, and maintaining cellular homeostasis. Protein ubiquitination, a key post-translational modification, is orchestrated by the sequential actions of three primary enzymes, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin protein ligase (E3), alongside the regulatory influence of deubiquitinases (DUBs) and various cofactors. The process begins with E1, which activates ubiquitin molecules. Subsequently, E2 receives the activated ubiquitin from E1 and transfers it to E3. E3, in turn, recognizes specific target proteins and facilitates the covalent attachment of ubiquitin from E2 to lysine residues on the target protein. Among the E2 enzymes, ubiquitin-conjugating enzyme E2O (UBE2O) stands out as a unique E2–E3 hybrid enzyme. UBE2O directly mediates the ubiquitination of a wide array of substrates, including 5′-AMP-activated protein kinase catalytic subunit alpha-2 (AMPKα2), MAX interactor 1 (Mxi1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog (c-Maf), among others. In this narrative review, we will explore the structural characteristics of UBE2O and elucidate its molecular functions. Additionally, we will summarize recent advancements in understanding the role of UBE2O in various tumors, Alzheimer’s disease (AD), and metabolic diseases. Finally, we will discuss the potential of targeting UBE2O as a novel therapeutic strategy for the treatment of human diseases. Full article
(This article belongs to the Special Issue Ubiquitylation and Deubiquitylation in Health and Diseases)
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21 pages, 5116 KiB  
Article
Patient Perspectives on Coordinated Care: Preliminary Results from the Implementation Stage Using Patient-Reported Experience Measures (PREMs)
by Beata Wieczorek-Wójcik, Anna Justyna Milewska, Dorota Kilańska, Aneta Kulma-Pytlak, Peter Iltchev, Aleksandra Gaworska-Krzemińska and Remigiusz Kozlowski
Healthcare 2025, 13(9), 1026; https://doi.org/10.3390/healthcare13091026 - 29 Apr 2025
Viewed by 251
Abstract
Background and Objectives: Integrated health services are health services that are managed and delivered in a way that ensures patients receive a continuum of health promotion, disease prevention, diagnosis, treatment, disease management, rehabilitation, and palliative care services at different levels and sites of [...] Read more.
Background and Objectives: Integrated health services are health services that are managed and delivered in a way that ensures patients receive a continuum of health promotion, disease prevention, diagnosis, treatment, disease management, rehabilitation, and palliative care services at different levels and sites of care within the health system, and according to their needs, throughout their life course. Assessing the effectiveness of their implementation, the perspective of the process participant—the patient—is examined. There are three main types of patient-reported measures: PROM, PREM and HLS. PREM (patient-reported experience measure) is a tool that allows the objective measurement of the patient’s experience related to healthcare services, for instance, the timeliness of visits or receiving recommendations. The aim of this study was to evaluate the coordinated care experienced by patients (PREMs) before and after the introduction of coordinated care, using the JOP-POP tool as a key measure. Materials and Methods: This longitudinal study was conducted in two stages. The first stage concerned the joining of the coordinated care program by the entity in which the study was conducted; the study was repeated six months after joining coordinated care (CC). At each stage of the study, the study group included 40 patients. The Shapiro–Wilk test was used to verify the normality of the distribution of quantitative variables. For statistical analysis, the Wilcoxon test for paired samples was used to compare two ordinal dependent variables. For independent variables, the Mann–Whitney and the Kruskal–Wallis ANOVA by ranks tests were used, with a post hoc test of multiple comparisons of mean ranks. Results: A statistically significant relationship (p = 0.00157) was observed between the number of chronic diseases and health status assessment before inclusion in coordinated care. The patients’ responses showed statistically significant improvement 6 months after the introduction of coordinated care (CC). The improvement in assessment was related to the time physicians spent with patients. The greatest improvement over 6 months was achieved in coordination of care and the smallest improvement was noted in the approach to the patient. Conclusions: The JOP-POP tool may be useful in future studies to assess patients’ experiences with implementing coordinated care. Full article
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14 pages, 557 KiB  
Article
Home-Based vs. Clinic-Based Rehabilitation After Joint Arthroplasty: A Prospective Matched Cohort Study
by Erminia Cofano, Filippo Familiari, Tommaso Mori, Michele Mercurio, Andrea Vescio, Alessandro Giorgio, Giorgio Gasparini and Giuseppe Calafiore
Appl. Sci. 2025, 15(9), 4937; https://doi.org/10.3390/app15094937 - 29 Apr 2025
Viewed by 188
Abstract
Background: Post-operative rehabilitation after total hip arthroplasty (THA) and total knee arthroplasty (TKA) is a crucial phase in the recovery process. The choice between clinic-based rehabilitation (CBR) and home-based rehabilitation (HBR) depends on the patient’s specific needs, available resources, and individual preferences. This [...] Read more.
Background: Post-operative rehabilitation after total hip arthroplasty (THA) and total knee arthroplasty (TKA) is a crucial phase in the recovery process. The choice between clinic-based rehabilitation (CBR) and home-based rehabilitation (HBR) depends on the patient’s specific needs, available resources, and individual preferences. This study aimed to compare CBR and HBR in terms of short-term post-operative functionality in patients who underwent THA and TKA. Methods: A prospective matched cohort study was performed on 120 patients who underwent primary THA and TKA; 60 patients underwent HBR, and 60 underwent CBR. Data gathered included instrumental activities of daily living (IADLs), as well as visual analogue scale (VAS), Vail Hip Score (VHS), and Western Ontario and McMaster Universities (WOMAC) questionnaire results. Results: Statistically significant recovery was found in terms of VAS, VHS, and WOMAC in the HBR and CBR groups (all p < 0.001) after THA and TKA. Multivariate regression analysis demonstrated that higher values of VHS and WOMAC at 1 month were associated with better values of VAS, VHS, and WOMAC preoperatively (r = 0.095, p = 0.021). Conclusion: HBR showed similar short-term postoperative outcomes when compared with CBR for patients who underwent total joint arthroplasty. Greater preoperative joint functionality, a lower level of pain, and a female gender predicted better functional outcomes at 1 month after surgery in both groups. Full article
(This article belongs to the Special Issue Orthopaedics and Joint Reconstruction: Latest Advances and Prospects)
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16 pages, 2704 KiB  
Article
Unveiling the Reaction Pathway of Oxidative Aldehyde Deformylation by a MOF-Based Cytochrome P450 Mimic
by Zehua Luo, Wentian Zhou, Junying Chen and Yingwei Li
Catalysts 2025, 15(5), 436; https://doi.org/10.3390/catal15050436 - 29 Apr 2025
Viewed by 147
Abstract
Understanding the reaction pathway of aldehyde deformylation catalyzed by natural enzymes has shown significance in developing synthetic methodologies and new catalysts in organic, biochemical, and medicinal chemistry. However, unlike other well-rationalized chemical processes catalyzed by cytochrome P450 (Cyt P450) superfamilies, the detailed mechanism [...] Read more.
Understanding the reaction pathway of aldehyde deformylation catalyzed by natural enzymes has shown significance in developing synthetic methodologies and new catalysts in organic, biochemical, and medicinal chemistry. However, unlike other well-rationalized chemical processes catalyzed by cytochrome P450 (Cyt P450) superfamilies, the detailed mechanism of the P450-catalyzed aldehyde deformylation is still controversial. Challenges lie in establishing synthetic models to decipher the reaction pathways, which normally are homogeneous systems for precisely mimicking the structure of the active sites in P450s. Herein, we report a heterogeneous Cyt P450 aromatase mimic based on a porphyrinic metal–organic framework (MOF) PCN-224. Through post-metalation of iron(II) triflate with the porphyrin unit, a five-coordinated FeII(Porp) compound could be afforded and isolated inside the resulting PCN-224(Fe) to mimic the heme active site in P450. This MOF-based P450 mimic could efficiently catalyze the oxidative deformylation of aldehydes to the corresponding ketones under room temperature using O2 as the sole oxidant and triethylamine as the electron source, analogous to the NADPH reductase. The catalyst could be completely recovered after the catalytic reaction without undergoing structural decomposition or compromising its reactivity, representing it as one of the most valid mimics of P450 aromatase from both the structural and functional aspects. A mechanistic study reveals a strong correlation between the catalytic activity and the Cα-H bond dissociation energy of the aldehyde substrates, which, in conjunction with various trapping experiments, confirms an unconventional mechanism initiated by hydrogen atom abstraction. Full article
(This article belongs to the Special Issue Recent Advances in Metal-Organic Framework Catalysts)
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14 pages, 5879 KiB  
Article
Effect of Post-Weld Heat Treatment Cooling Strategies on Microstructure and Mechanical Properties of 0.3 C-Cr-Mo-V Steel Weld Joints Using GTAW Process
by Syed Quadir Moinuddin, Mohammad Faseeulla Khan, Khaled Alnamasi, Skander Jribi, K. Radhakrishnan, Syed Shaul Hameed, V. Muralidharan and Muralimohan Cheepu
Metals 2025, 15(5), 496; https://doi.org/10.3390/met15050496 - 29 Apr 2025
Viewed by 164
Abstract
A total of 0.3%C-Cr-Mo-V steel, a high-strength alloy steel widely used in rocket motor housings, suspension systems in high-performance vehicles, etc., is noted due to its high strength-to-weight ratio. However, its high carbon equivalent (CE > 1%) makes it challenging to weld, as [...] Read more.
A total of 0.3%C-Cr-Mo-V steel, a high-strength alloy steel widely used in rocket motor housings, suspension systems in high-performance vehicles, etc., is noted due to its high strength-to-weight ratio. However, its high carbon equivalent (CE > 1%) makes it challenging to weld, as it is prone to brittle martensitic formation, which increases the risk of cracking and embrittlement. The present paper focuses on enhancing the microstructure and mechanical properties of 0.3% C-Cr-Mo-V steel by gas tungsten arc welded (GTAW) joints, utilizing post-weld heat treatment and cooling strategies (PWHTCS). A systematic experimental approach was employed to ensure a defect-free weld through dye penetrant testing (DPT) and X-ray radiography techniques. Subsequently, test specimens were extracted from the welded sections and subjected to PWHT protocols, including hardening, tempering, and rapid quenching using air and oil cooling (AC and OC, respectively) mediums. Results show that OC has enhanced tensile strength and hardness while simultaneously maintaining and improving ductility, ensuring a well-balanced combination of strength and toughness. Fractography analysis revealed ductile fracture in AC samples, whereas OC weldments exhibited a mixed ductile–brittle fracture mode. Thus, the findings demonstrate the critical role of PWHTCS, with OC, as an effective method for achieving enhanced mechanical performance and microstructural stability in high-integrity applications. Full article
(This article belongs to the Special Issue Welding and Joining of Advanced High-Strength Steels (2nd Edition))
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16 pages, 8001 KiB  
Article
Epitranscriptomic Analysis of the Ventral Hippocampus in a Mouse Model of Post-Traumatic Stress Disorder Following Deep Brain Stimulation Treatment of the Basolateral Amygdala
by Mingxi Ma, Hao Fan, Hui Zhang, Yao Yin, Yizheng Wang and Yan Gao
Brain Sci. 2025, 15(5), 473; https://doi.org/10.3390/brainsci15050473 - 29 Apr 2025
Viewed by 226
Abstract
Background: Basolateral amygdala (BLA) deep brain stimulation (DBS) has been shown to alleviate the symptoms of post-traumatic stress disorder (PTSD), but the specific mechanisms remain incompletely understood. The hippocampus, a brain region closely connected to the amygdala, plays a key role in the [...] Read more.
Background: Basolateral amygdala (BLA) deep brain stimulation (DBS) has been shown to alleviate the symptoms of post-traumatic stress disorder (PTSD), but the specific mechanisms remain incompletely understood. The hippocampus, a brain region closely connected to the amygdala, plays a key role in the pathological processes of PTSD. The N6-methyladenosine (m6A) methylation of RNAs in the hippocampus is known to play a significant role in regulating the brain’s response to stress and emotional disorders. Methods: This study aimed to comprehensively analyze the roles of transcriptome-wide m6A modifications of the hippocampus in the BLA DBS treatment of a PTSD mouse model using m6A sequencing. Results: Significant alterations in functional connectivity between the ventral hippocampus (vHPC) and BLA were observed in foot shock (FS) mice through functional magnetic resonance imaging (fMRI) analysis. Furthermore, we observed that the expression of the key m6A methyltransferase enzyme, METTL3, in the FS and BLA DBS groups was higher than that in the control group. At the same time, both FS and BLA DBS induced the widespread m6A methylation of RNAs in the vHPC. Gene ontology (GO) enrichment analysis revealed that FS altered methylation in metabolic, developmental, and cytoskeletal pathways, while BLA DBS targeted metabolic, cell cycle, and neuroplasticity-related genes. Additionally, BLA DBS reversed the aberrant methylation of genes associated with multiple functional pathways induced by FS, including those related to cholinergic transmission, sodium and calcium ion homeostasis, and stress hormone responsiveness. We identified a set of RNAs with methylation changes that were reversed by BLA DBS in the FS vs. Ctrl (control) comparison, including those associated with cholinergic transmission, sodium and calcium ion balance, and stress hormone response. Additionally, we detected several specific BLA DBS-related genes through MeRIP-qPCR, indicating that DBS influences crucial genes linked to calcium signaling and synaptic plasticity. Conclusions: We draw two conclusions from these findings: BLA DBS may alleviate PTSD-like symptoms by reversing FS-induced methylation changes and by altering the methylation levels of crucial genes. These findings indicate that epigenetic m6A modifications in the vHPC may play an important role in the amelioration of PTSD using BLA DBS. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
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17 pages, 4185 KiB  
Article
Squalane as a Promising Agent Protecting UV-Induced Inhibition of Collagen Biosynthesis and Wound Healing in Human Dermal Fibroblast
by Katarzyna Wolosik, Magda Chalecka, Gabriela Gasiewska, Jerzy Palka and Arkadiusz Surazynski
Molecules 2025, 30(9), 1964; https://doi.org/10.3390/molecules30091964 - 29 Apr 2025
Viewed by 232
Abstract
Squalane, a highly stable derivative of squalene, has received attention for its potential application in dermatology and cosmetics due to its biocompatibility, moisturizing properties, and antioxidant activity. This study investigates the effects of squalane on UVA-induced oxidative stress, inflammation, deregulation of collagen metabolism, [...] Read more.
Squalane, a highly stable derivative of squalene, has received attention for its potential application in dermatology and cosmetics due to its biocompatibility, moisturizing properties, and antioxidant activity. This study investigates the effects of squalane on UVA-induced oxidative stress, inflammation, deregulation of collagen metabolism, and some growth signaling pathways in human dermal fibroblasts (HDFs). It has been found that squalane at concentrations of 0.005–0.015% counteracted the UVA-induced inhibition of oxidative stress, collagen biosynthesis, prolidase activity, expression of the β1-integrin receptor, insulin-like growth factor-I receptor (IGFR), transforming growth factor-β (TGF-β), phosphorylated kinases ERK1/2, and increase in the expression of p38 kinase in HDFs. Moreover, squalane at the studied concentrations counteracted UVA-induced increase in the expression of NF-κB and COX-2 in HDFs, suggesting its anti-inflammatory activity. Interestingly, squalane augmented the UVA-induced expression of nuclear factor erythroid 2-related factor 2 (Nrf2). The functional significance of squalane activities was found in a model of wound healing in HDFs. Squalane at the studied concentrations stimulated fibroblast migration, facilitating the repair process following exposure of the cells to UVA radiation. These results demonstrate the ability of squalane to counteract UVA-induced cell damage and suggest its potential to support skin regeneration, highlighting its application in anti-aging, post-sun repair, and regenerative care formulations. Full article
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26 pages, 10104 KiB  
Article
Identification of Differentially Expressed Genes in Spinal Cord Injury
by Andrew Chang, Shevanka Dias Abeyagunawardene, Xiaohang Zheng, Haiming Jin, Qingqing Wang and Jiake Xu
Genes 2025, 16(5), 514; https://doi.org/10.3390/genes16050514 - 28 Apr 2025
Viewed by 371
Abstract
Background: Spinal cord injury (SCI) remains a profound medical challenge, with limited therapeutic options available. Studies focusing on individual molecular markers have limitations in addressing the complex disease process. Methods: This study utilizes RNA-sequencing (RNA-seq) to investigate the differentially expressed genes (DEGs) in [...] Read more.
Background: Spinal cord injury (SCI) remains a profound medical challenge, with limited therapeutic options available. Studies focusing on individual molecular markers have limitations in addressing the complex disease process. Methods: This study utilizes RNA-sequencing (RNA-seq) to investigate the differentially expressed genes (DEGs) in spinal cord tissue from a rat SCI model at 1 and 21 days post-injury (dpi). After data processing and analysis, a series of biological pathway enrichment analyses were performed using online tools DAVID and GSEA. Interactions among the enriched genes were studied using Cytoscape software to visualize protein–protein interaction networks. Results: Our analysis identified 595 DEGs, with 399 genes significantly upregulated and 196 significantly downregulated at both time points. CD68 was the most upregulated gene at 21 dpi, with a significant fold change at 1 dpi. Conversely, MPZ was the most downregulated gene. Key immune response processes, including tumor necrosis factor (TNF) production, phagocytosis, and complement cascades, as well as systemic lupus erythematosus (SLE)-associated pathways, were enriched in the upregulated group. The enriched pathways in the downregulated group were related to the myelin sheath and neuronal synapse. Genes of interest from the most significantly downregulated DEGs were SCD, DHCR24, PRX, HHIP, and ZDHHC22. Upregulation of Fc-γ receptor genes, including FCGR2B and FCGR2A, points to potential autoimmune mechanisms. Conclusions: Our findings highlight complex immune and autoimmune responses that contribute to ongoing inflammation and tissue damage post-SCI, underscoring new avenues for therapeutic interventions targeting these molecular processes. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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14 pages, 319 KiB  
Communication
Genomic Alterations of the Infectious Bronchitis Virus (IBV) Strain of the GI-23 Lineage Induced by Passages in Chickens and Quails
by Katarzyna Domanska-Blicharz, Joanna Sajewicz-Krukowska, Anna Lisowska, Justyna Opolska, Karolina Tarasiuk and Kamila Dziadek
Int. J. Mol. Sci. 2025, 26(9), 4200; https://doi.org/10.3390/ijms26094200 - 28 Apr 2025
Viewed by 131
Abstract
Infectious bronchitis virus (IBV) of the GI-23 lineage, which first emerged in the Middle East in the late 1990s, has since spread worldwide. The factors driving its expansion, whether human involvement, wild bird migration, or the virus’s biological traits, are still unclear. This [...] Read more.
Infectious bronchitis virus (IBV) of the GI-23 lineage, which first emerged in the Middle East in the late 1990s, has since spread worldwide. The factors driving its expansion, whether human involvement, wild bird migration, or the virus’s biological traits, are still unclear. This study aimed to trace the genome evolution of GI-23 IBV in chickens and its adaptability to quails, which are susceptible to both gamma- and deltacoronaviruses. Thirty specific-pathogen-free (SPF) birds, aged between two and three weeks, were used. Initially, three birds were inoculated with the G052/2016 IBV via the oculo-nasal route. On the third day post-infection (dpi), oropharyngeal swabs were collected from the whole group, pooled, and subsequently used to infect three next birds. This process was repeated nine more times during consecutive IBV passages (P-I–P-X), and eventually, virus sequencing was performed using Next-Generation Sequencing (NGS). The obtained results showed that quails were not susceptible to the IBV GI-23 lineage, as the virus RNA was detected in low amounts only during the first passage (QP-I) with no further detections in later rounds of IBV passaging. In chickens, only mild diarrhea symptoms appeared in a few individuals. The NGS analysis identified sixty-two single nucleotide variants (SNVs), thirty of which caused amino acid changes, twenty-eight were synonymous, and one SNV introduced a stop codon. Three SNVs were found in untranslated regions. However, none of these SNVs lasted beyond seven passages, with forty-four being unique SNVs. The Shannon entropy values measured during passages varied for pol1a, pol1b, S, 5a, 5b, and N genes, with overall genome complexity peaking at CP-VI and CP-X. The highest complexity was observed in the pol1a (CP-X) and S genes (CP-IV, CP-VI, CP-VIII, and CP-X). Along with the S gene that was under positive selection, eight codons in pol1a were also positively selected. These findings suggest that even in an adapted host, IBV variability does not stabilize without immune pressure, indicating continuous molecular changes within its genome. Full article
(This article belongs to the Section Molecular Microbiology)
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17 pages, 11651 KiB  
Article
Integration of Single-Cell and Bulk Transcriptome to Reveal an Endothelial Transition Signature Predicting Bladder Cancer Prognosis
by Jinyu Yang, Wangxi Wu and Xiaoli Tang
Biology 2025, 14(5), 486; https://doi.org/10.3390/biology14050486 - 28 Apr 2025
Viewed by 209
Abstract
Endothelial cells (ECs) are critical drivers of tumour progression, and their angiogenic process has been widely studied. However, the post-angiogenic transition of tip endothelial cells after sprouting remains insufficiently characterised. In this study, we utilised single-cell RNA sequencing analyses to identify a novel [...] Read more.
Endothelial cells (ECs) are critical drivers of tumour progression, and their angiogenic process has been widely studied. However, the post-angiogenic transition of tip endothelial cells after sprouting remains insufficiently characterised. In this study, we utilised single-cell RNA sequencing analyses to identify a novel EC transition signature associated with endothelial permeability, migration, metabolism, and vascular maturation. Within the transition pathway, we discovered a critical EC subpopulation, termed tip-to-capillary ECs (TC-ECs), that was enriched in tumour tissues. Comparative analyses of TC-ECs with tip and capillary ECs revealed distinct differences in pathway activity, cellular communication, and transcription factor activity. The EC transition signature demonstrated substantial prognostic significance, validated across multiple cancer cohorts from TCGA data, particularly in bladder cancer. Subsequently, we constructed a robust prognostic model for bladder cancer by integrating the EC transition signature with multiple machine-learning techniques. Compared with 31 existing models across the TCGA-BLCA, GSE32894, GSE32548, and GSE70691 cohorts, our model exhibited superior predictive performance. Stratification analysis identified significant differences between different risk groups regarding pathway activity, cellular infiltration, and therapeutic sensitivity. In conclusion, our comprehensive investigation identified a novel EC transition signature and developed a prognostic model for patient stratification, offering new insights into endothelial heterogeneity, angiogenesis regulation, and precision medicine. Full article
(This article belongs to the Special Issue Latest Research in Cancer Multi-Omics)
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