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Search Results (251)

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Keywords = VX-765

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12 pages, 1314 KB  
Article
Early Detection of Porcine Reproductive and Respiratory Syndrome Virus Outbreak: Combination of Methods
by Cunshuai Gao, Yunzhou Wang, Mengmeng Liu, Haotian Yang, Wenjing Jiao, Xuanpan Ding, Yuan Zhao and Honggang Fan
Vet. Sci. 2025, 12(12), 1198; https://doi.org/10.3390/vetsci12121198 - 15 Dec 2025
Viewed by 174
Abstract
The current application of the production data exponentially weighted moving average (EWMA) model can detect PRRSV outbreaks earlier than that of processing fluid (PF) testing; however, its advantages have not been fully reported. This study aimed to analyze various production parameters, including abortion, [...] Read more.
The current application of the production data exponentially weighted moving average (EWMA) model can detect PRRSV outbreaks earlier than that of processing fluid (PF) testing; however, its advantages have not been fully reported. This study aimed to analyze various production parameters, including abortion, off-feed, low appetite, and dead sows, on a daily basis following a PRRSV outbreak in an II-vx sow farm. The EWMA method was employed and the results were compared with the early detection of positive PF results. Differences in daily abnormal indicators across the three PRRSV status periods were analyzed. Additionally, this study evaluated the PRRSV detection rates in different sample types (AF, OS, and TBS) from aborted sows and compared the detection rates of different sample combinations using statistical tests. The 187-day study revealed that the first true positive (TP) alarm point for daily abortion sows occurred on day 107 and for off-feed sows on day 110. In contrast, the first RT-qPCR-positive result for PF was obtained on Day 122. The average values of daily abortions and off-feed sows in status I-A were significantly higher than those in status II-vx and I-B. Conversely, the average value of low appetite in status I-A was significantly lower than that in statuses II-vx and I-B. No significant differences were observed in the daily number of dead sows among the three groups. The RT-PCR detection rates varied significantly (p < 0.01) among the different sample types (AF, 43.04%; TBS, 65.82%; and OS, 74.68%), with amniotic fluid (AF) showing the lowest detection rate. Combining AF and oropharyngeal swabs (OS) samples yielded a higher detection rate than combining AF and TBS samples. Using the EWMA to monitor the daily number of aborted sows was effective for the early detection of PRRSV outbreaks. Full article
(This article belongs to the Special Issue Advances in Post-Outbreak Control and Eradication of Swine Diseases)
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19 pages, 3954 KB  
Article
Improvement of Structural, Elastic, and Magnetic Properties of Vanadium-Doped Lithium Ferrite
by W. R. Agami, H. M. Elsayed and A. M. Faramawy
Compounds 2025, 5(4), 54; https://doi.org/10.3390/compounds5040054 - 1 Dec 2025
Viewed by 172
Abstract
The influence of vanadium substitution on the structure, elastic, mechanical, and magnetic behavior of lithium ferrite (Li0.5+xVxFe2.5−2xO4; x = 0.00–0.2) was systematically studied. X-ray diffraction (XRD) was used to investigate the crystal structure, and infrared [...] Read more.
The influence of vanadium substitution on the structure, elastic, mechanical, and magnetic behavior of lithium ferrite (Li0.5+xVxFe2.5−2xO4; x = 0.00–0.2) was systematically studied. X-ray diffraction (XRD) was used to investigate the crystal structure, and infrared spectroscopy (IR) was used to determine the cation distribution between the two ferrite sublattices, in addition to the elastic and mechanical behavior of Li0.5+xVxFe2.5−2xO4 ferrites. X-ray analysis revealed a monotonic decrease in lattice parameter from 8.344 Å to 8.320 Å with increasing V5+ content, confirming lattice contraction and stronger metal–oxygen bonding. Despite a moderate increase in porosity (from 6.9% to 8.9%), the elastic constants C11 and C12 increased, indicating improved stiffness and reduced compressibility. The derived Young’s, bulk, and rigidity moduli rose with the doping of V5+. Correspondingly, the longitudinal, shear, and mean velocities (Vl, Vs, and Vm) increased. The Debye temperature also showed a linear rise from 705 K to 723 K with V5+ doping, directly reflecting enhanced lattice stiffness and phonon frequency. Furthermore, both the saturation magnetization (MS) and the initial permeability (μi) increased up to V5+ concentration x = 0.1 and then decreased. Curie temperature (TC) decreased with increasing V5+ concentration, while both the saturation magnetization (MS) and the initial permeability (μi) increased up to V5+ concentration x = 0.1 and then decreased, while the coercivity (HC) showed the reverse trend. These results confirm that V5+ incorporation significantly enhances the Li ferrite, improving its elastic strength, lattice energy, thermal stability, and magnetically controlling properties and making them suitable for a variety of daily uses such as magneto-elastic sensors, high-frequency devices, and applications requiring mechanically robust ferrite materials. Full article
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18 pages, 443 KB  
Article
Detection Method for Closed-Source VxWorks Memory Protection Mechanisms Based on Dynamic Instruction Translation Monitoring
by Yixin Guo, Youwei Zhang and Yan Cao
Electronics 2025, 14(22), 4382; https://doi.org/10.3390/electronics14224382 - 10 Nov 2025
Viewed by 399
Abstract
In embedded real-time operating systems, memory protection mechanisms are critical for ensuring system security. However, for closed-source platforms like VxWorks, widely used in critical domains such as aerospace and industrial control, existing methods struggle to effectively detect the runtime status of memory protection [...] Read more.
In embedded real-time operating systems, memory protection mechanisms are critical for ensuring system security. However, for closed-source platforms like VxWorks, widely used in critical domains such as aerospace and industrial control, existing methods struggle to effectively detect the runtime status of memory protection mechanisms without access to source code. In contrast, research on memory protection mechanisms (e.g., ASLR and DEP) in Windows and Linux has developed into a mature field, highlighting the research intensity in this area. This paper proposes a detection method tailored for VxWorks, which instruments function call instructions at the QEMU TCG layer to dynamically reconstruct call chains and combines this with static modeling to automatically identify the activation status of key memory protection mechanisms, such as text segment write protection and stack non-executability. To validate the method’s effectiveness, three groups of firmware samples were designed, representing scenarios with no protection, partial protection, and full protection enabled. Experimental results demonstrate that the method delivers stable and reliable detection across various configurations, with no false positives or false negatives. Furthermore, open-source test cases enhance the credibility and reproducibility of the experiments. This approach, characterized by automation, non-intrusiveness, and high adaptability, provides an efficient tool for verifying the security configurations of closed-source embedded systems. Full article
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15 pages, 1315 KB  
Article
New Role of Protein Misfolding Corrector in the ER Stress-Inflammation Axis: Possible Therapeutic Indication in Neuronal and Epithelial Tumor Cells
by Michela Pecoraro, Adele Serra, Maria Julia Lamberti, Maria Pascale and Silvia Franceschelli
Int. J. Mol. Sci. 2025, 26(22), 10846; https://doi.org/10.3390/ijms262210846 - 8 Nov 2025
Viewed by 570
Abstract
Protein misfolding diseases are characterized by structurally abnormal proteins that lose their functionality, resulting in cellular and tissue dysfunction. Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and Huntington’s disease, share a common etiopathogenesis characterize by the accumulation of misfolded proteins. These proteins autonomously [...] Read more.
Protein misfolding diseases are characterized by structurally abnormal proteins that lose their functionality, resulting in cellular and tissue dysfunction. Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and Huntington’s disease, share a common etiopathogenesis characterize by the accumulation of misfolded proteins. These proteins autonomously aggregate within neuronal cells, triggering inflammation and cell death. The accumulation of misfolded proteins triggers endoplasmic reticulum (ER) stress, leading to alter Ca2+ homeostasis. This prolonged stress condition induces the cleavage of procaspase 4 which is resident in ER and activates NF-kB pathway activation, leading to inflammatory responses and cell death. In this study, the efficacy of the drug Vx-445 (Elexacaftor), used in the pharmacological treatment of cystic fibrosis, was assessed in human adenocarcinomic basal alveolar epithelial (A549) and neuronal (SH-SY5Y) cell lines, where ER stress was induced by Thapsigargin. The aim was to assess whether the corrector was able to reduce ER stress by restoring cellular homeostasis and, probably, the proper folding of misfolded proteins and reducing the inflammatory response triggered by these events. Therefore, protein levels of IkBα, p-STAT 3 and COXII were analyzed by flow cytofluorimetry, while Ca2+ content was measured by spectrofluorimetry. The results obtained suggest a significant effect of Vx-445 in restoring cellular homeostasis, leading to reduced expression of inflammation-related proteins, such as IL-6, tested by ELISA. Although preliminary, these results encourage further studies to explore the potential repurpose of Vx-445 as a therapeutic candidate for conditions involving ER stress and chronic inflammatory diseases associated with protein misfolding, beyond its current use in cystic fibrosis. Full article
(This article belongs to the Special Issue Protein Folding, Misfolding, and Related Diseases)
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18 pages, 4261 KB  
Article
Diagnostic Performance of Autofluorescence for Oral Lesions: A Comparison Between a Postgraduate and an Expert Clinician
by Alessandro Antonelli, Cristina D’Antonio, Anna Martina Battaglia, Riccardo Finamore, Antonio Madonna, Vincenzo Greco, Vincenzo Cosentino, Selene Barone, Flavia Biamonte, Amerigo Giudice and Francesco Bennardo
Dent. J. 2025, 13(11), 512; https://doi.org/10.3390/dj13110512 - 3 Nov 2025
Viewed by 513
Abstract
Background/Objectives: Autofluorescence (AF) is a widely used adjunctive tool in the detection of oral potentially malignant disorders (OPMDs) and malignant lesions, but its performance can be influenced by clinicians’ experiences. This study aimed to examine how AF influences diagnostic decision-making and performances [...] Read more.
Background/Objectives: Autofluorescence (AF) is a widely used adjunctive tool in the detection of oral potentially malignant disorders (OPMDs) and malignant lesions, but its performance can be influenced by clinicians’ experiences. This study aimed to examine how AF influences diagnostic decision-making and performances of a novice clinician compared with those of an experienced examiner. Methods: A total of 80 patients with oral lesions participated in this cross-sectional study. Each underwent a standard oral examination (OE) followed by an assessment with the VELscope® System Vx (LED Medical Diagnostics Inc., Burnaby, BC, Canada), independently conducted by an expert clinician (E) and a postgraduate dentist (PD), both blinded to each other’s results. Biopsy and histopathological analysis provided the reference diagnosis. After every examination, lesions were categorized as either “Risk of Malignancy” (RM) or “No Risk of Malignancy” (NRM). Results: Based on OE, PD identified 39 RM lesions, while E 29. AF with VELscope® identified an additional 12 RM lesions for the PD and 7 for the E that were not suspected on OE alone. Combining OE with VELscope® improved sensitivity (PD: 90.9%; E: 95.4%) and negative predictive value (PD: 91.7%; E: 97.6%), while decreasing specificity (PD: 37.9%; E: 70.7%) and positive predictive value (PD: 35.7%; E: 55.3%) compared with OE alone. Conclusions: AF increases diagnostic sensitivity, particularly for less experienced clinicians, while offering moderate advantages for experts. Nevertheless, the corresponding decline in specificity emphasizes the need for cautious interpretation. AF should be incorporated as a complementary tool within structured diagnostic pathways, accompanied by adequate training, and cannot replace histopathological confirmation or clinical expertise. Full article
(This article belongs to the Special Issue Oral Pathology: Current Perspectives and Future Prospects)
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29 pages, 3538 KB  
Article
Mitochondrial Fragmentation Induced by the CFTR Modulators Lumacaftor and Ivacaftor in Immortalized Cystic Fibrosis Cell Lines
by Camila Dib, Pablo A. Iglesias González, María de los Ángeles Aguilar, Guillermo L. Taminelli, Tatiana Limpias del Valle, Nadia E. Nuñez, Analía G. Karadayian, Tomás A. Santa-Coloma and Ángel G. Valdivieso
Cells 2025, 14(20), 1601; https://doi.org/10.3390/cells14201601 - 15 Oct 2025
Viewed by 1413
Abstract
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene, which encodes a cAMP-activated chloride channel essential for epithelial function. Beyond its canonical role, evidence suggests CFTR also influences mitochondrial function. Previous studies have identified CFTR- and Cl-dependent [...] Read more.
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene, which encodes a cAMP-activated chloride channel essential for epithelial function. Beyond its canonical role, evidence suggests CFTR also influences mitochondrial function. Previous studies have identified CFTR- and Cl-dependent genes, including MTND4 and CISD1, which are downregulated in CF cells and play a critical role in mitochondrial function. CF cells exhibit altered mitochondrial complex I (mCx-I) activity and impaired electron transport chain function, although the underlying mechanisms remain unclear. In this study, the impact of the CFTR modulators lumacaftor (VX-809) and ivacaftor (VX-770) on mitochondrial morphology and function was investigated in heterozygous ΔF508/W1282X CF IB3-1 cells. Combined treatment with VX-809 (10 μM, CFTR corrector) and VX-770 (0.1 μM, CFTR potentiator) induced a fragmented mitochondrial morphology in both CF and CF expressing wt-CFTR cells, without affecting cell viability or mitochondrial membrane potential (ΔΨm). While individual treatments differentially modulated ROS production and ΔΨm, these effects were not statistically significant under combined treatment. These results highlight a previously unrecognized role for CFTR modulators in shaping mitochondrial morphology. A better understanding of these effects may reveal novel mechanisms underlying the regulation of mitochondrial structure and function. Full article
(This article belongs to the Special Issue Mechanisms of Respiratory Diseases)
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19 pages, 4254 KB  
Article
Microstructure and Mechanical and Corrosion Behavior of Novel High-Entropy CoCrFeNiSiVx (x = 0.25; 0.5; 0.75; 1.0) Alloys
by Rafał Babilas, Monika Spilka, Katarzyna Młynarek-Żak, Adrian Radoń, Wojciech Łoński, Krzysztof Matus and Jakub Bicz
Materials 2025, 18(19), 4616; https://doi.org/10.3390/ma18194616 - 6 Oct 2025
Viewed by 691
Abstract
In this work, a series of novel high-entropy alloys CoCrFeNiSiVx (x = 0.25; 0.5; 0.75; 1.0) with an intermetallic compound structure was proposed. The effect of vanadium addition on the structure, as well as selected mechanical and corrosion properties, was investigated. In [...] Read more.
In this work, a series of novel high-entropy alloys CoCrFeNiSiVx (x = 0.25; 0.5; 0.75; 1.0) with an intermetallic compound structure was proposed. The effect of vanadium addition on the structure, as well as selected mechanical and corrosion properties, was investigated. In the case of the CoCrFeNiSiV0.25 alloy, the structural analysis revealed the formation of a dual-phase structure consisting of Fe1.812V0.907Si0.906-type and Fe5Ni3Si2-type intermetallic phases. The increase in vanadium concentration results in the crystallization of one Fe1.812V0.907Si0.906 intermetallic phase detected by the X-ray diffraction method. The increase in vanadium content had a beneficial influence on the corrosion resistance of CoCrFeNiSiVx alloys in 3.5% NaCl. The CoCrFeNiSiV alloy exhibited the lowest corrosion current density of 0.17 μA/cm2 and the highest corrosion potential of −0.228 V. The hardness of the alloys investigated increased with vanadium content, reaching 1006 HV for the equimolar alloy. In turn, the lowest friction coefficient of 0.63 ± 0.06 was obtained for the CoCrFeNiSiV0.75 alloy. The abrasive, fatigue, and oxidative wear were identified as the main wear mechanisms. Full article
(This article belongs to the Section Metals and Alloys)
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14 pages, 3057 KB  
Article
Microstructure and Compressive Properties of (Ti51Zr25Cu6Be18)100−xVx Bulk Metallic Glass Matrix Composites
by Xinhua Huang, Junnan Li, Guang Wang, Bin Chen, Chenghao Wei and Yuejun Ouyang
Crystals 2025, 15(10), 838; https://doi.org/10.3390/cryst15100838 - 26 Sep 2025
Viewed by 422
Abstract
Metallic glass alloys exhibit excellent properties, yet suffer from poor room-temperature plasticity, a limitation that restricts their engineering applications. Bulk metallic glass matrix composites (BMGMCs) have proven effective in enhancing the plasticity of metallic glasses, and the addition of alloying elements serves as [...] Read more.
Metallic glass alloys exhibit excellent properties, yet suffer from poor room-temperature plasticity, a limitation that restricts their engineering applications. Bulk metallic glass matrix composites (BMGMCs) have proven effective in enhancing the plasticity of metallic glasses, and the addition of alloying elements serves as a key strategy to regulate their microstructure and optimize the properties of these composites. This study aims to investigate the effects of a vanadium (V) addition on the mechanical properties and microstructure of Ti-based BMGMCs, while exploring the underlying mechanism of V’s influence. Using (Ti51Zr25Cu6Be18)100−xVx (x = 0, 4, 8, 12, 16, 20) BMGMCs as test specimens, microstructural characterization was performed via X-ray diffraction (XRD) and scanning electron microscopy (SEM), and compressive mechanical properties were tested. The results indicate that a V addition refines dendrites without altering the phase composition, which remains composed of β-Ti crystals and an amorphous matrix. With the increase in V content, the compressive plastic strain shows a trend of first increasing and then decreasing; when x = 12, the specimen exhibits the maximum compressive plastic strain, reaching 7.9%. Additionally, the volume fraction of the crystalline phase gradually increases with increasing V content. This study clarifies the mechanism by which V regulates the microstructure and properties of Ti-based BMGMCs, thereby providing theoretical and experimental insights for optimizing alloy compositions to enhance the mechanical performance. Full article
(This article belongs to the Section Inorganic Crystalline Materials)
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32 pages, 7470 KB  
Article
Consensus-Guided Construction of H5N1-Specific and Universal Influenza a Multiepitope Vaccines
by Marco Palma
Biology 2025, 14(10), 1327; https://doi.org/10.3390/biology14101327 - 25 Sep 2025
Viewed by 906
Abstract
Background/Objectives: Influenza A viruses—including highly pathogenic H5N1—remain a global threat due to rapid evolution, zoonoses, and pandemic potential. Strain-specific vaccines targeting variable antigens often yield limited, short-lived immunity. The HA receptor-binding domain (RBD), a functionally constrained and immunologically relevant region, is a promising [...] Read more.
Background/Objectives: Influenza A viruses—including highly pathogenic H5N1—remain a global threat due to rapid evolution, zoonoses, and pandemic potential. Strain-specific vaccines targeting variable antigens often yield limited, short-lived immunity. The HA receptor-binding domain (RBD), a functionally constrained and immunologically relevant region, is a promising target for broad and subtype-focused vaccines. We aimed to design multiepitope constructs targeting conserved HA-RBD and adjacent domains to elicit robust, durable, cross-protective responses. Methods: Extensive sequence analyses (>20,000 H5N1 and >190,000 influenza A sequences) were used to derive consensus sequences. Three HA-based candidates were developed: (i) EpitoCore-HA-VX, a multi-epitope construct containing CTL, HTL, and B-cell epitopes from the H5N1 HA-RBD; (ii) StructiRBD-HA-VX, incorporating a conformationally preserved RBD segment; and (iii) FusiCon-HA-VX, targeting the conserved HA fusion peptide shared across subtypes. Two external HA comparators—a 400-aa HA fragment and the literature-reported HA-13–263-Fd-His—were analyzed under the same pipeline. The workflow predicted epitopes; evaluated antigenicity, allergenicity, toxicity, conservation, and HLA coverage; generated AlphaFold models; performed TLR2/TLR4 docking with pyDockWEB; and carried out interface analysis with PDBsum; and C-ImmSim simulations. Results: Models suggested stable, energetically favorable TLR2/TLR4 interfaces supported by substantial binding surfaces and complementary electrostatic/desolvation profiles. Distinct docking patterns indicated receptor-binding flexibility. Immune simulations predicted strong humoral responses with modeled memory formation and, for the H5N1-focused designs, cytotoxic T-cell activity. All candidates and comparators were predicted to be antigenic, non-allergenic, and non-toxic, with combined HLA coverage approaching global breadth. Conclusions: This study compares three design strategies within a harmonized framework—epitope collation, structure-preserved RBD, and fusion-peptide targeting—while benchmarking against two HA comparators. EpitoCore-HA-VX and StructiRBD-HA-VX showed promise against diverse H5N1 isolates, whereas FusiCon-HA-VX supported cross-subtype coverage. As these findings are model-based, they should be interpreted qualitatively; nonetheless, the integrated, structure-guided approach provides an adaptable path for advancing targeted H5N1 and broader influenza A vaccine concepts. Full article
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21 pages, 32435 KB  
Article
Structure and Magnetic Properties of Vanadium-Doped Heusler Ni-Mn-In Alloys
by Dmitry Kuznetsov, Elena Kuznetsova, Alexey Mashirov, Alexander Kamantsev, Denis Danilov, Georgy Shandryuk, Sergey Taskaev, Irek Musabirov, Ruslan Gaifullin, Maxim Kolkov, Victor Koledov and Pnina Ari-Gur
Nanomaterials 2025, 15(19), 1466; https://doi.org/10.3390/nano15191466 - 24 Sep 2025
Cited by 2 | Viewed by 735
Abstract
The crystal structure, texture, martensitic transformation, and magnetic properties of magnetic shape-memory Heusler alloys of Ni51−xMn33.4In15.6Vx (x = 0; 0.1; 0.3; 0.5; 1) were investigated. Experimental studies of the magnetic properties and meta-magnetostructural transition (martensitic transition—MT) [...] Read more.
The crystal structure, texture, martensitic transformation, and magnetic properties of magnetic shape-memory Heusler alloys of Ni51−xMn33.4In15.6Vx (x = 0; 0.1; 0.3; 0.5; 1) were investigated. Experimental studies of the magnetic properties and meta-magnetostructural transition (martensitic transition—MT) confirm the main sensitivity of the martensitic transition temperature to vanadium doping and to an applied magnetic field. This makes this family of shape-memory alloys promising for use in numerous applications, such as magnetocaloric cooling and MEMS technology. Diffuse electron scattering was analyzed, and the structures of the austenite and martensite were determined, including the use of TEM in situ experiments during heating and cooling for an alloy with a 0.3 at.% concentration of V. In the austenitic state, the alloys are characterized by a high-temperature-ordered phase of the L21 type. The images show nanodomain structures in the form of tweed contrast and contrast from antiphase domains and antiphase boundaries. The alloy microstructure in the temperature range from the martensitic finish to 113 K consists of a six-layer modulated martensite, with 10 M and 14 M modulation observed in local zones. The morphology of the double structure of the modulated martensite structure inherits the morphology of the nanodomain structure in the parent phase. This suggests that it is possible to control the structure of the high-temperature austenite phase and the temperature of the martensitic transition by alloying and/or rapidly quenching from the high-temperature phase. In addition, attention is paid to maintaining fine interface structures. High-resolution transmission electron microscopy showed good coherence along the austenite–martensite boundary. Full article
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19 pages, 3634 KB  
Article
Chlorogenic Acid and VX765 Alleviate Deoxynivalenol-Induced Enterohepatic Injury and Lipid Metabolism Disorders by Improving Intestinal Microecology
by Tao Wen, Sirui Li, Huijun Guo, Jinbo Wang, Xinru Zhang and Chunyang Wang
Toxins 2025, 17(9), 467; https://doi.org/10.3390/toxins17090467 - 18 Sep 2025
Viewed by 770
Abstract
Widespread contamination of deoxynivalenol (DON) in cereals and feed threatens global food safety. This study investigated the effects of Chlorogenic acid (CGA) and VX765 on DON-induced enterohepatic injury. A total of 48 female mice were divided into four groups: control (normal saline), DON [...] Read more.
Widespread contamination of deoxynivalenol (DON) in cereals and feed threatens global food safety. This study investigated the effects of Chlorogenic acid (CGA) and VX765 on DON-induced enterohepatic injury. A total of 48 female mice were divided into four groups: control (normal saline), DON (1 mg/kg.bw), CGA (100 mg/kg.bw CGA + 1 mg/kg.bw DON), and VX765 (100 mg/kg.bw VX765 + 1 mg/kg.bw DON). After 28-day gavage period, the results showed that CGA and VX765 reduced DON-induced intestinal barrier damage. Metabolomics data revealed that CGA and VX765 restored cecal microbiota structure and alleviated DON-induced hepatic injury and lipid metabolic disorders by reshaping intestinal microbiota. Retrograde endocannabinoid signaling was identified as a critical pathway for cecal microbial metabolism and hepatic lipid regulation mediated by CGA and VX765. Additionally, CGA and VX765 reversed the upregulation of IMPA, CDS2, DGKA, NDUFS8, and MAPK1 mRNA and protein expression levels induced by DON via the microbiota-gut-liver axis. Full article
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30 pages, 3080 KB  
Article
A High-Acceptance-Rate VxWorks Fuzzing Framework Based on Protocol Feature Fusion and Memory Extraction
by Yichuan Wang, Jiazhao Han, Xi Deng and Xinhong Hei
Future Internet 2025, 17(8), 377; https://doi.org/10.3390/fi17080377 - 21 Aug 2025
Viewed by 1073
Abstract
With the widespread application of Internet of Things (IoT) devices, the security of embedded systems faces severe challenges. As an embedded operating system widely used in critical mission scenarios, the security of the TCP stack in VxWorks directly affects system reliability. However, existing [...] Read more.
With the widespread application of Internet of Things (IoT) devices, the security of embedded systems faces severe challenges. As an embedded operating system widely used in critical mission scenarios, the security of the TCP stack in VxWorks directly affects system reliability. However, existing protocol fuzzing methods based on network communication struggle to adapt to the complex state machine and grammatical rules of the TCP. Additionally, the lack of a runtime feedback mechanism for closed-source VxWorks systems leads to low testing efficiency. This paper proposes the vxTcpFuzzer framework, which generates structured test cases by integrating the field features of the TCP. Innovatively, it uses the memory data changes of VxWorks network protocol processing tasks as a coverage metric and combines a dual anomaly detection mechanism (WDB detection and heartbeat detection) to achieve precise anomaly capture. We conducted experimental evaluations on three VxWorks system devices, where vxTcpFuzzer successfully triggered multiple potential vulnerabilities, verifying the framework’s effectiveness. Compared with three existing classic fuzzing schemes, vxTcpFuzzer demonstrates significant advantages in test case acceptance rates (44.94–54.92%) and test system abnormal rates (23.79–34.70%) across the three VxWorks devices. The study confirms that protocol feature fusion and memory feedback mechanisms can effectively enhance the depth and efficiency of protocol fuzzing for VxWorks systems. Furthermore, this approach offers a practical and effective solution for uncovering TCP vulnerabilities in black-box environments. Full article
(This article belongs to the Special Issue Secure Integration of IoT and Cloud Computing)
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25 pages, 2042 KB  
Article
CFTR Modulators Counteract F508del CFTR Functional Defects in a Pancreatic Epithelial Model of Cystic Fibrosis
by Alessandra Ludovico and Debora Baroni
Life 2025, 15(8), 1315; https://doi.org/10.3390/life15081315 - 19 Aug 2025
Viewed by 1600
Abstract
Cystic fibrosis is a multisystem disorder caused by mutations in the CFTR gene that lead to impaired ion and fluid transport across secretory epithelia. Although the therapeutic impact of CFTR modulators has been extensively studied in airway epithelia, their efficacy in extra-pulmonary tissues, [...] Read more.
Cystic fibrosis is a multisystem disorder caused by mutations in the CFTR gene that lead to impaired ion and fluid transport across secretory epithelia. Although the therapeutic impact of CFTR modulators has been extensively studied in airway epithelia, their efficacy in extra-pulmonary tissues, such as the pancreas, has been less explored. This study evaluated the effects of the CFTR modulators, VX770 (ivacaftor), VX661 (tezacaftor), and VX445 (elexacaftor), administered either individually or in combination, on CFPAC-1 cells, a pancreatic ductal epithelial cell line derived from a cystic fibrosis patient harboring the F508del CFTR mutation. The cells were cultured and differentiated onto porous supports, and a panel of functional parameters was assessed. These included transepithelial electrical conductance, fluid reabsorption, apical surface fluid pH, protein concentration, and microviscosity, the latter analyzed with multiple particle tracking. To simulate a pro-inflammatory micro-environment, the cells were preconditioned with lipopolysaccharide (LPS). Treatment with VX661 and VX445 resulted in significant improvement in epithelial function, with the triple combination producing the most pronounced rescue. Pro-inflammatory stimulation by LPS increased the production of cytokine IL6, IL-8, and IL-1β, as well as the protein content of the apical surface fluid. Despite the LPS pro-inflammatory stimulus, CFTR modulators preserved or slightly enhanced their efficacy in restoring CFTR-mediated ion and fluid transport. However, they did not reduce cytokine expression under pro-inflammatory conditions. Collectively, these findings show that CFTR modulators can restore critical aspects of cystic fibrosis pancreatic epithelial physiology in vitro, even under pro-inflammatory stress, supporting their potential relevance beyond the airway disease. Full article
(This article belongs to the Special Issue Cystic Fibrosis: A Disease with a New Face)
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21 pages, 9707 KB  
Article
Shallot virus X p42 Protein Expressed in Concert with Virus Movement Proteins Is a Suppressor of Two Plant Antiviral Defense Mechanisms
by Denis A. Chergintsev, Alexander A. Lezzhov, Ekaterina A. Lazareva, Anastasia K. Atabekova, Anna D. Solovieva, Sergey Y. Morozov and Andrey G. Solovyev
Plants 2025, 14(16), 2552; https://doi.org/10.3390/plants14162552 - 16 Aug 2025
Viewed by 1021
Abstract
The genomes of viruses in the Allexivirus genus encode the p42 protein, which is considered the hallmark of the genus. The functions of p42 have not yet been studied experimentally and cannot be predicted based on sequence similarity, as p42-related proteins are not [...] Read more.
The genomes of viruses in the Allexivirus genus encode the p42 protein, which is considered the hallmark of the genus. The functions of p42 have not yet been studied experimentally and cannot be predicted based on sequence similarity, as p42-related proteins are not found among known cell or viral proteins. Here, p42 of Shallot virus X (ShVX), the type allexivirus, is demonstrated to be translated via a leaky scanning mechanism on a template comprising three “triple gene block” (TGB) transport genes and the p42 gene. Sequence analysis shows that this p42 expression mechanism is conserved in the vast majority of allexiviruses. p42 binds single-stranded RNA (ssRNA) but not double-stranded RNA (dsRNA) in vitro and localizes to the cytoplasm in association with microtubules and microtubule-bound bodies. In transient expression assays, p42 exhibits weak but detectable suppression of silencing induced by ssRNA but not by dsRNA. In addition, p42 suppresses silencing in the context of virus infection. Furthermore, p42 inhibits nonsense-mediated RNA decay (NMD) induced by a long 3′-terminal untranslated region of mRNA. Taken together, these findings provide initial evidence that the ShVX TGB/p42 gene module functions as a single genomic unit in terms of protein expression, that p42 acts as a suppressor of NMD and silencing, and that it may have multiple roles, while the precise biological significance of p42 in these roles remains to be experimentally confirmed. Full article
(This article belongs to the Special Issue Plant Virology and Disease Management in Crops)
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Article
Comparing Close-Field and Open-Field Autorefractometry and Subjective Refraction
by Veronica Noya-Padin, Noelia Nores-Palmas, Belen Sabucedo-Villamarin, Maria J. Giraldez, Eva Yebra-Pimentel and Hugo Pena-Verdeal
J. Clin. Med. 2025, 14(16), 5680; https://doi.org/10.3390/jcm14165680 - 11 Aug 2025
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Abstract
Background/Objectives: Autorefractometers are valuable tools in clinical practice, but their accuracy is often questioned, especially in the pediatric population. This study aimed to compare refraction data from open-field and close-field autorefractometers and subjective refraction without using cycloplegia. Methods: A total of [...] Read more.
Background/Objectives: Autorefractometers are valuable tools in clinical practice, but their accuracy is often questioned, especially in the pediatric population. This study aimed to compare refraction data from open-field and close-field autorefractometers and subjective refraction without using cycloplegia. Methods: A total of 50 eyes of 50 participants (19 males and 31 females, 11.8 ± 1.56 years) were evaluated. In a single visit, objective refraction was performed using NVision-K 5001 (open-field) and Visionix VX120 (close-field) autorefractometers, and subjective refraction using the fogging technique. Differences between procedures were assessed for sphere, spherical equivalent, and cylindrical vectors J0 and J45 using the Friedman test, followed by the post hoc Wilcoxon test as needed. Results: Significant differences were found in the sphere between the three procedures (all p ≤ 0.032). For the spherical equivalent, the Visionix VX120 differed significantly with the other two techniques (both p < 0.001), whereas no significant differences were found between NVision-K 5001 and subjective refraction (p = 0.193). Finally, no significant differences were observed for J0 and J45 vectors among the procedures (both p ≥ 0.166). Conclusions: There are certain discrepancies between autorefractometers and the subjective assessment of refractive error, most evident in measurements taken with the close-field device, possibly due to greater accommodative stimulation. However, in contexts such as visual screening or as a preliminary guide in the clinic, the values obtained by autorefractometry can provide useful information. Full article
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