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18 pages, 1311 KB  
Article
Heat Capacity and Thermodynamic Properties of Photocatalitic Bismuth Tungstate, Bi2WO6
by Bogusław Onderka and Anna Kula
Metals 2025, 15(11), 1174; https://doi.org/10.3390/met15111174 - 23 Oct 2025
Abstract
The photocatalytic activity of Bi2WO6 Aurivillius phase has been widely exploited for the degradation of a wide range of gaseous and aqueous molecules, as well as microorganisms, under the influence of visible irradiation. Strategies for the development of doped and [...] Read more.
The photocatalytic activity of Bi2WO6 Aurivillius phase has been widely exploited for the degradation of a wide range of gaseous and aqueous molecules, as well as microorganisms, under the influence of visible irradiation. Strategies for the development of doped and co-doped bismuth tungstate materials require the thermodynamic data on this phase. The heat capacity of bismuth tungstate, Bi2WO6, was investigated using a DSC microcalorimeter on polycrystalline powder samples in the temperature range from 313 to 1103 K (40–830 °C) in two separate runs. The samples were synthesized by solid-state reaction from pure binary oxides at 1033 K (760 °C) in a platinum crucible with cover. The high temperature Cp(T) data were fitted by the Maier–Kelley equation and, from this relation, the standard molar heat capacity of γ-Bi2WO6 polymorph was estimated to be at 298.15 K 176.8 ± 3.9 J·K−1·mol−1. A reversible second-order transition of Bi2WO6 phase was observed in the experimental temperature range, with a peak close to 940 K (667 °C). Additionally, the extrapolation of Cp(T) to 0 K was proposed using a method based on the multiple Einstein model. Thermodynamic properties (heat capacity Cp(T), entropy S°(T), enthalpy H°(T), Gibbs energy G°(T)) of crystalline γ-Bi2WO6 were calculated in the temperature range of 298.15–1123 K (25–850 °C). Full article
(This article belongs to the Section Extractive Metallurgy)
18 pages, 2204 KB  
Article
Data-Driven Yield Improvement in Upstream Bioprocessing of Monoclonal Antibodies: A Machine Learning Case Study
by Breno Renato Strüssmann, Anderson Rodrigo de Queiroz and Lars Hvam
Processes 2025, 13(11), 3394; https://doi.org/10.3390/pr13113394 - 23 Oct 2025
Abstract
The increasing demand for monoclonal antibody (mAb) therapeutics has intensified the need for more efficient and consistent biomanufacturing processes. We present a data-driven, machine-learning (ML) approach to exploring and predicting upstream yield behavior. Drawing on industrial-scale batch records for a single mAb product [...] Read more.
The increasing demand for monoclonal antibody (mAb) therapeutics has intensified the need for more efficient and consistent biomanufacturing processes. We present a data-driven, machine-learning (ML) approach to exploring and predicting upstream yield behavior. Drawing on industrial-scale batch records for a single mAb product from a contract development and manufacturing organization, we applied regression models to identify key process parameters and estimate production outcomes. Random forest regression, gradient boosting machine, and support vector regression (SVR) were evaluated to predict three yield indicators: bioreactor final weight (BFW), harvest titer (HT), and packed cell volume (PCV). SVR outperformed other models for BFW prediction (R2 = 0.978), while HT and PCV were difficult to model accurately with the available data. Exploratory analysis using sequential least-squares programming suggested parameter combinations associated with improved yield estimates relative to historical data. Sensitivity analysis highlighted the most influential process parameters. While the findings demonstrate the potential of ML for predictive, data-driven yield improvement, the results should be interpreted as an exploratory proof of concept rather than a fully validated optimization framework. This study highlights the need to incorporate process constraints and control logic, along with interpretable or hybrid modeling frameworks, to enable practical deployment in regulated biomanufacturing environments. Full article
(This article belongs to the Section Biological Processes and Systems)
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19 pages, 1366 KB  
Article
Characterization of Chemically-Induced Endogenous Retroviral Particles in the CHO-K1 Cell Line
by Nicholas B. Mattson, Trent J. Bosma, Yamei Gao, Sandra M. Fuentes, Pei-Ju Chin and Arifa S. Khan
Viruses 2025, 17(11), 1408; https://doi.org/10.3390/v17111408 - 23 Oct 2025
Abstract
The Chinese hamster ovary K1 cell line (CHO-K1) constitutively produces retroviral-like particles (RVLPs) containing reverse transcriptase (RT) activity, which, thus far, have not been shown to be infectious. Since infectious retroviruses have been reported in other rodent species, this study was undertaken to [...] Read more.
The Chinese hamster ovary K1 cell line (CHO-K1) constitutively produces retroviral-like particles (RVLPs) containing reverse transcriptase (RT) activity, which, thus far, have not been shown to be infectious. Since infectious retroviruses have been reported in other rodent species, this study was undertaken to investigate the presence of latent, infectious, endogenous retroviruses (ERVs) in CHO-K1 cells by using chemical induction assays and detection of activated virus using the highly sensitive, product-enhanced RT (PERT) assay, with subsequent infectivity analysis in cell lines of different species, including human. The results demonstrated activation of A-type and C-type retroviral particles based on transmission electron microscopy and increased production of cell-free RT-particles after treatment of the cells with 5-iodo-2′-deoxyuridine and 5-azacytidine, which was greater with dual treatment than with each inducer alone. Induction of A- and C-type particles was confirmed in dual-drug-treated CHO-K1 cells by long-read high-throughput sequence (HTS) analysis. Infectivity studies performed by inoculating human A549, HEK-293, and MRC-5 cells; African green monkey Vero cells; Mus dunni cells; and CHO-K1 cells with supernatant containing RT-particles from dual-treated CHO-K1 cells indicated the absence of a replicating retrovirus in supernatant from extended cell culture using the PERT assay. Furthermore, short-read HTS analysis did not show evidence of integration of retroviral sequences in inoculated A549 and 293 cells. The overall results showed no evidence for latent, infectious, endogenous RVLPs in CHO-K1 cells. Full article
(This article belongs to the Special Issue The Diverse Regulation of Transcription in Endogenous Retroviruses)
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14 pages, 2616 KB  
Article
GC Content and Thermal Stability of Double-Stranded RNA: Fragments of Microsporidia Vairimorpha ceranae and Nosema bombycis AT-Rich Genes Are Sensitive to Standard Heat Treatment
by Ruslan R. Fadeev, Sergey A. Timofeev, Igor V. Senderskiy and Viacheslav V. Dolgikh
Int. J. Mol. Sci. 2025, 26(21), 10270; https://doi.org/10.3390/ijms262110270 - 22 Oct 2025
Abstract
Heating at 95 °C or boiling E. coli HT115 (DE3) cells is often used to extract heterologous dsRNA or kill bacteria, although these temperatures cause dsRNA denaturation and destruction. In this study, we examined the risk of degradation of dsRNA fragments of AT-rich [...] Read more.
Heating at 95 °C or boiling E. coli HT115 (DE3) cells is often used to extract heterologous dsRNA or kill bacteria, although these temperatures cause dsRNA denaturation and destruction. In this study, we examined the risk of degradation of dsRNA fragments of AT-rich genes at high temperature. The expression of dsRNA fragments of AT-rich genes encoding DNA replication enzymes from the microsporidia Vairimorpha ceranae and Nosema bombycis in E. coli HT115 (DE3) was accompanied by heating the bacteria at 95 °C for 30 min. In contrast to four control fragments with normal GC content, the AT-rich dsRNAs of microsporidia were destroyed by this treatment. The in vitro synthesis and heating of the studied dsRNAs showed the degradation of both microsporidia and control fragments. The thermal degradation of in vitro-synthesized control dsRNA with a normal GC content of 47.6% was prevented by the addition of 2 × YT media, NaCl, or low concentrations of MgSO4. This demonstrates the important role of mono- and divalent cations in stabilizing heated fragments and helps explain the preservation of their integrity and RNAi-initiating activity despite the treatment of bacteria at temperatures that denature dsRNA. Feeding Colorado potato beetle larvae with the same in vitro-synthesized dsRNA containing fragments of three Leptinotarsa decemlineata genes showed that their thermal destruction was accompanied by a decrease in pest-suppressing activity. No dsRNA degradation was observed at 80 °C or after E. coli sonication, and these treatments, as well as increasing cation content, may help to avoid the degradation of heat-sensitive dsRNA. Full article
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10 pages, 671 KB  
Article
Peripheral Serotonergic Activation in Severe Aortic Stenosis: A Biochemical Perspective
by Denisa Bianca Mercean, Raluca Tomoaia, Ioana Berindan-Neagoe, Liviuţa Budişan, Dana Pop, Adela Mihaela Șerban, Carmen Stanca Melincovici and Carmen Mihaela Mihu
Int. J. Mol. Sci. 2025, 26(21), 10250; https://doi.org/10.3390/ijms262110250 - 22 Oct 2025
Abstract
The involvement of the serotoninergic system in the pathogenesis of calcific aortic stenosis introduced a novel dimension to our understanding of this complex cardiovascular condition. This study aimed to assess serotonin (5-HT) and its main metabolite, 5-Hydroxyindoleacetic acid (5-HIAA) in patients with severe [...] Read more.
The involvement of the serotoninergic system in the pathogenesis of calcific aortic stenosis introduced a novel dimension to our understanding of this complex cardiovascular condition. This study aimed to assess serotonin (5-HT) and its main metabolite, 5-Hydroxyindoleacetic acid (5-HIAA) in patients with severe aortic valve stenosis (AS). The study employed a case–control design, including 76 patients who underwent transthoracic echocardiography, computed tomography (CT), and peripheral blood sampling. Serum concentrations of 5-HT and 5-HIAA were quantified using enzyme-linked immunosorbent assay (ELISA). The severe aortic valve stenosis group exhibited significantly elevated levels of 5-HT and 5-HIAA compared to the control group (5-HT 1066.5 ng/mL (IQR = 961.9–1112 ng/mL) vs. 977.4 ng/mL (IQR = 394.3–1097.9 ng/mL); p = 0.034 and 5-HIAA 57 ± 12.7 ng/mL vs. 47.5 ± 15.3 ng/mL; p = 0.004, respectively). Receiver operating characteristic (ROC) analysis revealed that 5-HT predicted severe AS with a sensitivity of 73.7% and specificity of 50% at a cut-off level > 973.5 ng/mL, whereas 5-HIAA exhibited a sensitivity of 86.8% and specificity of 47.4% when a cut-off level > 45.49 ng/mL was used. This study showed a significant elevation in the 5-HT and 5-HIAA among patients with severe AS, further supporting the potential involvement of the peripheral serotonergic system in the pathophysiology of this condition. Full article
(This article belongs to the Section Biochemistry)
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19 pages, 1616 KB  
Article
Thermal Cycling Stimulation via Nasal Inhalation Attenuates Aβ25–35-Induced Cognitive Deficits in C57BL/6 Mice
by Guan-Bo Lin, Hsu-Hsiang Liu, Yu-Yi Kuo, You-Ming Chen, Fang-Tzu Hsu, Yu-Wei Wang, Yi Kung, Chien Ching and Chih-Yu Chao
Int. J. Mol. Sci. 2025, 26(20), 10236; https://doi.org/10.3390/ijms262010236 - 21 Oct 2025
Abstract
Alzheimer’s disease (AD) remains a significant public health challenge, with current treatments limited partly due to the difficulty of delivering therapeutics across the blood–brain barrier (BBB). The nose-to-brain (N-2-B) pathway offers a promising alternative to circumvent the BBB, but no drugs have yet [...] Read more.
Alzheimer’s disease (AD) remains a significant public health challenge, with current treatments limited partly due to the difficulty of delivering therapeutics across the blood–brain barrier (BBB). The nose-to-brain (N-2-B) pathway offers a promising alternative to circumvent the BBB, but no drugs have yet been clinically applied via this route for AD. Mild stress is thought to activate intrinsic protective mechanisms against neurodegeneration, but traditional methods lack specificity and practicality. To address this, we propose the inhalation of mildly heated air as thermal stimulation, which utilizes the N-2-B pathway to induce mild stress and stimulate cerebral activity. This study employs thermal cycling-hyperthermia (TC-HT) in developing thermal cycling-stimulation via nasal inhalation (TCSNI), providing cyclic stimulation to maintain pathway activity while minimizing thermal injury. In C57BL/6 mice, TCSNI showed no adverse olfactory effects. In β-amyloid (Aβ)-treated mice, TCSNI significantly enhanced cognitive performance in Y-maze and novel object recognition (NOR) assessments, suggesting cognitive improvement. Mice hippocampal protein analyses indicated a reduction in Aβ accumulation, alongside increased expression of heat shock protein 70 (HSP70), insulin-degrading enzyme (IDE), and phosphorylated Akt (p-Akt). These results suggest that N-2-B-delivered TCSNI effectively modulates protein expression and enhances cognitive function, highlighting its potential for further exploration in AD treatment. Full article
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14 pages, 1324 KB  
Article
Enhancing Lower-Body Power in Highly Trained Female Athletes: Effects of Velocity-Based Strength Training
by Christoph Schärer, Caterina Barloggio and Jan Seiler
J. Funct. Morphol. Kinesiol. 2025, 10(4), 411; https://doi.org/10.3390/jfmk10040411 - 21 Oct 2025
Abstract
Background: Only a limited number of studies have examined the effects of short-term, strength–speed-oriented velocity-based training (VBT) on lower-body power in female junior volleyball players and elite female artistic gymnasts. The present study aimed to investigate the impact of a four-week VBT intervention [...] Read more.
Background: Only a limited number of studies have examined the effects of short-term, strength–speed-oriented velocity-based training (VBT) on lower-body power in female junior volleyball players and elite female artistic gymnasts. The present study aimed to investigate the impact of a four-week VBT intervention on jump performance and force–velocity characteristics in these athletes. Methods: Seven junior female volleyball players (age: 17.4 ± 0.9 years; height: 179.4 ± 6.5 cm; weight: 74.01 ± 3.5 kg) (top-league team members), and seven elite female artistic gymnasts (age: 17.6 ± 2.9 years; height: 159.6 ± 7.2 cm; weight: 59.3 ± 6.3 kg) (National Team members) completed two weekly training sessions for four weeks, each consisting of four sets of six repetitions of parallel back squats (PBSs) and hip thrusts (HTs). Training loads were regulated using barbell velocity targets (PBSs: 0.46–0.72 m/s; HTs: 0.36–0.60 m/s). Pre- and post-intervention assessments included loaded (15–60% body mass) and unloaded squat jumps (SJs) and countermovement jumps (CMJs) to determine peak power output, jump height, and force–velocity profiles. Results: Volleyball players showed significant improvements in peak power predominantly during loaded SJs (SJ45%: +5.5%, p < 0.01; SJ60%: +5.7%, p < 0.05), whereas gymnasts exhibited greater gains in loaded CMJs (CMJ60%: +7.7%, p < 0.01). In contrast, unloaded SJ and CMJ performances remained largely unchanged for all athletes. Both groups demonstrated a significantly steeper post-intervention force–velocity profile (p < 0.001), indicating an enhanced capacity to produce force at lower movement velocities under external loading. Conclusions: Strength–speed-oriented VBT was effective in improving power production under loaded conditions but had limited transfer to unloaded jump performance. These findings highlight the necessity of subsequent training blocks emphasizing high-velocity, sport-specific movements to optimize explosive performance. Future studies should further investigate low-velocity-loss training protocols as a potential means of enhancing unloaded jump outcomes. Full article
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29 pages, 1401 KB  
Review
Using Low-Intensity Focused Ultrasound to Treat Depression and Anxiety Disorders: A Review of Current Evidence
by Ao Du, Manli Huang, Zheng Wang, Hetong Zhou, Huilong Duan, Shaohua Hu and Yinfei Zheng
Brain Sci. 2025, 15(10), 1129; https://doi.org/10.3390/brainsci15101129 - 21 Oct 2025
Abstract
Background: Depression and anxiety disorders impact millions globally. In recent years, low-intensity focused ultrasound (LIFU), characterized by its high precision, deep penetration, and non-invasive nature, has garnered significant interest in neuroscience and clinical practice. To enhance understanding of its effects on mood, [...] Read more.
Background: Depression and anxiety disorders impact millions globally. In recent years, low-intensity focused ultrasound (LIFU), characterized by its high precision, deep penetration, and non-invasive nature, has garnered significant interest in neuroscience and clinical practice. To enhance understanding of its effects on mood, therapeutic availability in treatment of depression/anxiety disorders, and potential mechanisms, a systematic review of studies investigating the emotional impact of LIFU on depressive/anxious-like animal models, healthy volunteers, and patients with depression or anxiety disorders has been undertaken. Methods: Relevant papers published before 15 July 2025 were searched across four databases: Web of Science, PubMed, Science Direct, and Embase. A total of 28 papers which met the inclusion and exclusion criteria are included in this review. Results: Our findings indicate that LIFU reversed the depressive/anxious-like behaviors in the animal models and showed antidepressant/anti-anxiety effects among the state-of-art clinical studies. For example, immobility time in FST or TST is reduced in depressive animal models, and HRSD/BAI scales are improved in human studies. Key molecules such as BDNF/5-HT are found restored in animal models, and FC between key brain areas related to depression/anxiety is modulated after LIFU treatment. Notably, no brain tissue damage was observed in animal studies, and only mild adverse effects (such as dizziness and vomiting) were noted in a few human studies. Conclusions: The studies using LIFU to treat depression and anxiety remain in the preliminary stage. The mechanisms underlying LIFU’s mood effects—such as activation or inhibition of specific brain regions or neural circuits, anti-inflammatory effects, alterations in functional connectivity, synaptic plasticity, neurotransmitter levels, and BDNF—remain incompletely understood and warrant further investigation. Nevertheless, the LIFU technique holds promise for regulating both cortical and subcortical brain areas implicated in depression/anxiety disorders as a precise neuromodulation tool. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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12 pages, 5179 KB  
Article
Effect of the Cooling Rate on the Solidification Structure and Phase of a 2:17 Samarium–Cobalt Alloy
by Zhi Zhu, Yikun Fang, Wei Wu and Bo Zhao
Alloys 2025, 4(4), 23; https://doi.org/10.3390/alloys4040023 - 21 Oct 2025
Abstract
Understanding the way samarium–cobalt alloys solidify at varying cooling rates and the regularities in alloying element distribution is crucial for optimizing subsequent homogenization and annealing processes, leading to an enhancement in the overall quality of the product. The study investigates the effects of [...] Read more.
Understanding the way samarium–cobalt alloys solidify at varying cooling rates and the regularities in alloying element distribution is crucial for optimizing subsequent homogenization and annealing processes, leading to an enhancement in the overall quality of the product. The study investigates the effects of rapid water-cooled copper mold (600 °C/min), medium-speed copper mold (100 °C/min), and slow furnace cooling (10 °C/min) on the microstructural evolution, element distribution, and phase transformation of samarium–cobalt (Sm-Co) alloys. The results of the research show that the phase transition temperatures obtained via differential scanning calorimetry (DSC) closely matched those observed in situ by high-temperature laser scanning confocal microscopy (HT-LSCM). Higher cooling rates resulted in notable dendritic refinement and reduced precipitate size. Elemental analysis revealed that Co and Fe exhibited negative segregation, whereas Sm, Cu, and Zr showed positive segregation, with segregation intensity increasing alongside the cooling rate. The principal phases identified included Cu-rich and Zr-rich constituents, the matrix phase, and a gray phase morphologically distinct from the matrix. These correspond to the (Sm, Co, Fe, Cu, Zr)5 phase, (Sm, Zr)(Co, Fe, Cu)3 phase, Sm2(Co, Fe, Cu, Zr)17 phase, and Sm(Co, Fe, Cu, Zr)7 phase. The phase constitution remained consistent across different cooling rates. Full article
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17 pages, 2360 KB  
Article
Gas–Water Two-Phase Flow Mechanisms in Deep Tight Gas Reservoirs: Insights from Nanofluidics
by Xuehao Pei, Li Dai, Cuili Wang, Junjie Zhong, Xingnan Ren, Zengding Wang, Chaofu Peng, Qihui Zhang and Ningtao Zhang
Nanomaterials 2025, 15(20), 1601; https://doi.org/10.3390/nano15201601 - 21 Oct 2025
Abstract
Understanding gas–water two-phase flow mechanisms in deep tight gas reservoirs is critical for improving production performance and mitigating water invasion. However, the effects of pore-throat-fracture multiscale structures on gas–water flow remain inadequately understood, particularly under high-temperature and high-pressure conditions (HT/HP). In this study, [...] Read more.
Understanding gas–water two-phase flow mechanisms in deep tight gas reservoirs is critical for improving production performance and mitigating water invasion. However, the effects of pore-throat-fracture multiscale structures on gas–water flow remain inadequately understood, particularly under high-temperature and high-pressure conditions (HT/HP). In this study, we developed visualizable multiscale throat-pore and throat-pore-fracture physical nanofluidic chip models (feature sizes 500 nm–100 μm) parameterized with Keshen block geological data in the Tarim Basin. We then established an HT/HP nanofluidic platform (rated to 240 °C, 120 MPa; operated at 100 °C, 100 MPa) and, using optical microscopy, directly visualized spontaneous water imbibition and gas–water displacement in the throat-pore and throat-pore-fracture nanofluidic chips and quantified fluid saturation, front velocity, and threshold pressure gradients. The results revealed that the spontaneous imbibition process follows a three-stage evolution controlled by capillarity, gas compression, and pore-scale heterogeneity. Nanoscale throats and microscale pores exhibit good connectivity, facilitating rapid imbibition without significant scale-induced resistance. In contrast, 100 μm fractures create preferential flow paths, leading to enhanced micro-scale water locking and faster gas–water equilibrium. The matrix gas displacement threshold gradient remains below 0.3 MPa/cm, with the cross-scale Jamin effect—rather than capillarity—dominating displacement resistance. At higher pressure gradients (~1 MPa/cm), water is efficiently expelled to low saturations via nanoscale throat networks. This work provides an experimental platform for visualizing gas–water flow in multiscale porous media under ultra-high temperature and pressure conditions and offers mechanistic insights to guide gas injection strategies and water management in deep tight gas reservoirs. Full article
(This article belongs to the Special Issue Nanomaterials and Nanotechnology for the Oil and Gas Industry)
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24 pages, 2791 KB  
Article
Clinical and Therapeutic Insights into Sepsis: A Retrospective Observational Study of Inflammatory Markers, and Outcomes
by Dragoș Ștefan Lazăr, Adina-Alexandra Nanu, Ilie-Andrei Condurache, Casandra Bulescu, Catrinel Tudosie, Alexandra Ioana Grigore, Corneliu Petru Popescu and Simin Aysel Florescu
Biomedicines 2025, 13(10), 2566; https://doi.org/10.3390/biomedicines13102566 - 21 Oct 2025
Abstract
Introduction: Sepsis is a life-threatening condition caused by dysregulated host responses to infection, leading to organ failure and high mortality. Early recognition, especially in vulnerable populations, remains challenging due to variable presentations. Key biomarkers like CRP, procalcitonin, fibrinogen, and neutrophil-to-lymphocyte ratio (NLR) aid [...] Read more.
Introduction: Sepsis is a life-threatening condition caused by dysregulated host responses to infection, leading to organ failure and high mortality. Early recognition, especially in vulnerable populations, remains challenging due to variable presentations. Key biomarkers like CRP, procalcitonin, fibrinogen, and neutrophil-to-lymphocyte ratio (NLR) aid in diagnosis, monitoring, and prognosis. Rapid identification and targeted therapy are critical, particularly amid rising antimicrobial resistance. This study aims to analyze the relationship between early biomarker levels and patient outcomes, focusing on mortality risk prediction within the first week of hospitalization. Methods: A retrospective study of 198 sepsis patients hospitalized in Bucharest, Romania, between January and December 2024, analyzing inflammatory biomarkers at admission—T0, 48–72 h—T1, and one week—T2, to identify predictors of clinical outcomes. Results: In patients under 65 years old, fibrinogen, CRP, and NLR significantly decreased from T0 to T2, especially in survivors. In contrast, patients over 65 years old showed less consistent biomarker changes, with higher mortality associated, with comorbidities such as heart failure and cancer. Overall, early reductions in inflammatory markers correlated with better outcomes, highlighting their prognostic value in sepsis management. Conclusions: In sepsis patients over 65 years old, a stable or rising neutrophil-to-lymphocyte ratio (NLR) and fibrinogen levels after the first week of hospitalization may indicate a poor prognosis, whereas decreasing levels suggest a better chance of survival. Full article
(This article belongs to the Section Microbiology in Human Health and Disease)
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18 pages, 795 KB  
Article
Assessment of Maternal Exposure to Mycotoxins During Pregnancy Through Biomarkers in Fetal and Neonatal Tissues
by João Thiago Aragão Fermiano, Sher Ali, Sana Ullah, Vanessa Theodoro Rezende, Roice Eliana Rosim, Fernando Gustavo Tonin, Walusa Assad Gonçalves Ferri, Alessandra Cristina Marcolin, Leandra Naira Zambelli Ramalho, Carlos Augusto Fernandes de Oliveira and Fernando Silva Ramalho
Toxins 2025, 17(10), 518; https://doi.org/10.3390/toxins17100518 - 21 Oct 2025
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Abstract
This study aimed to conduct a first evaluation of maternal exposure to mycotoxins during pregnancy in Brazil through quantification of biomarkers in liver and serum samples from stillborn and neonates autopsied in the Clinical Hospital of Ribeirão Preto, state of São Paulo. Liver [...] Read more.
This study aimed to conduct a first evaluation of maternal exposure to mycotoxins during pregnancy in Brazil through quantification of biomarkers in liver and serum samples from stillborn and neonates autopsied in the Clinical Hospital of Ribeirão Preto, state of São Paulo. Liver tissue (n = 43) and serum (n = 38) samples were collected from 43 patients and analyzed for biomarkers of aflatoxins (AFs), ochratoxin A (OTA), fumonisins (FBs), zearalenone (ZEN), deoxynivalenol (DON), T-2 and HT-2 toxins by ultra-performance liquid chromatography coupled to tandem mass spectrometry. In total, 9 samples of liver (20.9%) and 33 serum (86.8%) had quantifiable levels of mycotoxins. In liver samples, aflatoxin M1 (AFM1) was quantified in two samples (median level: 0.38 ng/g), while four samples had OTA residues (median: 0.31 ng/g) and one contained ZEN (3.6 ng/g). Compared with liver tissue, serum samples had higher occurrence rates of mycotoxins, particularly AFM1, OTA and ZEN. Nineteen serum samples (50%) contained 2–4 types of mycotoxins, indicating an effective transplacental transfer of major mycotoxins during pregnancy. Median levels of AFM1, OTA, FB1, ZEN, DON, T-2 and HT-2 toxins in serum samples were 0.48, 3.39, 30.6, 10.53, 5.71, 2.85 and 10.84 ng/mL, respectively. The most frequent cause of death was extreme prematurity (33% of cases), followed by preterm premature rupture of membranes (16% of cases) and morphological abnormalities (42% of cases). Results of this trial suggest potential associations between dietary mycotoxins and congenital anomalies. Further research should clarify the transplacental transfer of mycotoxins and their association with toxic effects during human prenatal development. Full article
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20 pages, 3601 KB  
Article
Investigating Apple Rubbery Wood Virus 2: HTS-Based Detection in Hungary and Involvement of sRNA-Based Regulation Processes During Its Infection
by Almash Jahan and Éva Várallyay
Viruses 2025, 17(10), 1394; https://doi.org/10.3390/v17101394 - 20 Oct 2025
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Abstract
Pomme fruits are propagated vegetatively, thereby facilitating frequent viral transmission. The causative agent of apple rubbery wood disease, apple rubbery wood virus 2 (ARWV2), can infect apple and pear. The branches of ARWV2-infected, symptomatic trees are flexible due to the decreased lignification of [...] Read more.
Pomme fruits are propagated vegetatively, thereby facilitating frequent viral transmission. The causative agent of apple rubbery wood disease, apple rubbery wood virus 2 (ARWV2), can infect apple and pear. The branches of ARWV2-infected, symptomatic trees are flexible due to the decreased lignification of the xylem. In this research, we reanalysed our small RNA (sRNA) HTS datasets to survey the presence of ARWV2 in Hungary. Validation of HTS using RT-PCR revealed infection in several cultivars. The following RT-PCR-based survey revealed the infection of 17 trees, including not only apple, but also pears, one quince, and a rootstock, without showing any rubbery wood symptoms. Analysis of the sRNA datasets allowed us to profile the sRNA pattern of ARWV2-infected and non-infected trees, and characterise the differential expression pattern of vsiRNAs, sRNAs, and miRNAs targeting the lignin biosynthetic pathway. The results confirmed that the gene-expression changes in the genes that regulate lignification cannot be directly correlated with the presence of the virus, which can explain its frequent latent presence. The variable titre and sequence of the virus, and mixed-infection status of the trees, make its reliable diagnostics challenging, which could be achieved as a result of further research. Full article
(This article belongs to the Special Issue Emerging and Reemerging Plant Viruses in a Changing World)
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24 pages, 2036 KB  
Review
Cardiovascular Risk Factors Involved in Hemorrhagic Transformation After Intravenous Thrombolytic Therapy in Patients with Acute Ischemic Stroke
by Ileana Neacă, Cristina Elena Negroiu, Iulia Tudorașcu, Raluca Dănoiu, Sânziana Godeanu, Suzana Dănoiu and Despina Manuela Toader
Int. J. Mol. Sci. 2025, 26(20), 10186; https://doi.org/10.3390/ijms262010186 - 20 Oct 2025
Viewed by 106
Abstract
In line with AHA/ASA guidance, intravenous alteplase has served as the standard first-line reperfusion treatment in acute ischemic stroke (AIS). Hemorrhagic transformation (HT) is a common spontaneous complication after thrombolytic therapy for AIS with increased mortality. Restoration of flow in an occluded artery [...] Read more.
In line with AHA/ASA guidance, intravenous alteplase has served as the standard first-line reperfusion treatment in acute ischemic stroke (AIS). Hemorrhagic transformation (HT) is a common spontaneous complication after thrombolytic therapy for AIS with increased mortality. Restoration of flow in an occluded artery can precipitate blood–brain barrier breakdown and heighten the risk of HT. However, the pathogenesis of HT is multifactorial, and identifying patients at high risk after recanalization therapy (RT) has a defining role in ensuring optimal treatment. At the same time, it is still under debate how these patients can best be identified based on clinical and biological characteristics. Preventing HT will become increasingly essential. In this review, our primary objective was to identify research focused on the cardiovascular risk factors predicting HT after AIS treated with thrombolytics, as this may help develop targeted treatment strategies and diminish the risk of HT. Full article
(This article belongs to the Special Issue The Molecular Basis of Vascular Pathology)
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18 pages, 616 KB  
Article
Efficacy of Subsequent Therapy in Patients with Hormone-Positive Advanced Breast Cancer with Disease Progression After CDK4/6 Inhibitor Therapy: Multicenter Real-Life Data
by Buket Şahin Çelik, Aslı Geçgel, Oğuzcan Özkan, Nargiz Majidova, Buket Erkan Özmarasalı, Gözde Ağdaş, İsmail Bayrakçı, Türkkan Evrensel and Erhan Gökmen
J. Clin. Med. 2025, 14(20), 7376; https://doi.org/10.3390/jcm14207376 - 18 Oct 2025
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Abstract
Objectives: The aim of this study was to evaluate the effect of different systemic therapies after CDK4/6 inhibitor therapy on survival outcomes in HR+/HER2− metastatic breast cancer (MBC) patients. Methods: In this retrospective multicenter study, patients who continued chemotherapy (CT), everolimus [...] Read more.
Objectives: The aim of this study was to evaluate the effect of different systemic therapies after CDK4/6 inhibitor therapy on survival outcomes in HR+/HER2− metastatic breast cancer (MBC) patients. Methods: In this retrospective multicenter study, patients who continued chemotherapy (CT), everolimus + endocrine therapy (HT), and other hormonotherapy after treatment with a CDK4/6 inhibitor were compared. Clinicopathological data and survival outcomes were analyzed. Statistical analyses were performed using the SPSS v25 program, survival analyses were performed using the Kaplan–Meier method, and comparisons were made using the log-rank test. Results: A total of 145 patients were included in the study. The groups were similar in terms of baseline characteristics such as age, menopausal status, histology, stage, adjuvant treatment status, and metastatic spread pattern. The rate of recurrent disease was significantly higher in the CT and Everolimus + HT groups compared to the “Other” group (p = 0.027). However, there was no significant difference between the groups in terms of PFS and OS in the general population (p > 0.05). In subgroup analyses, OS was significantly longer in the everolimus + HT group compared to the CT group in those with recurrence duration ≥ 1 year and stable disease course > 6 months during CDK4/6 inhibitor treatment (p = 0.010 and p = 0.039). Conclusions: Although there was no significant difference in overall survival regarding the choice of treatment after a CDK4/6 inhibitor, everolimus + endocrine therapy was observed to have a positive effect on survival in some subgroups. This finding supports individualized treatment. Full article
(This article belongs to the Section Oncology)
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