Search Results (256)

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

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

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

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

In this work, a series of novel high-entropy alloys CoCrFeNiSiV_x (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 CoCrFeNiSiV_0.25 alloy, the structural analysis revealed the formation of a dual-phase structure consisting of Fe_1.812V_0.907Si_0.906-type and Fe₅Ni₃Si₂-type intermetallic phases. The increase in vanadium concentration results in the crystallization of one Fe_1.812V_0.907Si_0.906 intermetallic phase detected by the X-ray diffraction method. The increase in vanadium content had a beneficial influence on the corrosion resistance of CoCrFeNiSiV_x 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 CoCrFeNiSiV_0.75 alloy. The abrasive, fatigue, and oxidative wear were identified as the main wear mechanisms. Full article

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−xV_x (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

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

The crystal structure, texture, martensitic transformation, and magnetic properties of magnetic shape-memory Heusler alloys of Ni_51−xMn_33.4In_15.6V_x (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

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

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

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

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

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

Systematic Background/Objectives: Type 1 diabetes mellitus (T1DM) is an autoimmune condition in which pancreatic β-cells are selectively destroyed, predominantly by autoreactive T lymphocytes. Despite decades of research, the achievement of durable immune tolerance remains elusive. This review presents a historically grounded and forward-looking perspective on the evolution of immunotherapy in T1DM, from early immunosuppressive interventions to advanced precision-based cellular approaches. Specifically, we focus on systemic immunosuppressants (e.g., corticosteroids, cyclosporine), monoclonal antibodies (e.g., anti-CD3, anti-IL-1, anti-TNF), regulatory cell-based approaches (e.g., Tregs, CAR-Tregs, MDSCs), and β-cell replacement strategies using stem cell-derived islets. Methods: We analyzed major clinical and translational milestones in immunotherapy for T1DM, with particular attention to the transition from broad immunosuppression to targeted modulation of immune pathways. Emerging data on cell-based therapies, artificial intelligence (AI)-driven stratification, and personalized intervention timing have been incorporated to provide a comprehensive overview of current and future directions. Results: Initial therapies such as corticosteroids and cyclosporine offered proof-of-concept for immune modulation, yet suffered from relapse and toxicity. The introduction of monoclonal antibodies (e.g., teplizumab) marked a shift toward immune-specific intervention, particularly in stage 2 preclinical T1DM. More recent approaches include low-dose IL-2, checkpoint modulation, and antigen-specific tolerance strategies. Cellular therapies such as Treg adoptive transfer, chimeric antigen receptor Tregs (CAR-Tregs), and stem cell-derived islet replacements (e.g., VX-880) have shown promise in preserving β-cell function and modulating autoimmunity. Myeloid-derived suppressor cells (MDSCs), although still preclinical, represent a complementary avenue for immune tolerance induction. Concurrently, AI-based models are emerging as tools to stratify risk and personalize immunotherapeutic timing, enhancing trial design and outcome prediction. Conclusions: In conclusion, the historical progression from broad immunosuppression to precision-driven strategies underscores the importance of stage-specific, mechanism-based interventions in T1DM. The convergence of targeted biologics, regenerative cell therapies, and β-cell replacement approaches, supported by AI-enabled patient stratification, offers a realistic path toward durable immune tolerance and functional β-cell preservation. Continued integration of these modalities, coupled with rigorous long-term evaluation, will be essential to transform these scientific advances into sustained clinical benefit. Full article

Objectives: To compare the objective refraction of young hyperopes obtained by two wavefront autorefractors with identical measurement principles but different optical designs: a monocular closed-field (VX 120) and a binocular open-field (Eye Refract), both developed by the same manufacturer (Visionix; Pont-de-l’Arche, France). Methods: A randomized, cross-sectional study was carried out with 37 hyperopic participants (18.2 ± 7.8 years; range 8 to 31 years). Each participant underwent two measurement sessions (one with and one without cycloplegia), during which three measurements were taken per autorefractor (monocular and binocular). Refractive variables (M, J0, and J45) were analyzed in one randomly selected eye. Results: The spherical equivalent (M) showed significant differences between autorefractors under noncycloplegic and cycloplegic conditions (p < 0.001). Without cycloplegia, the binocular autorefractor measured +0.45 (+1.49, −0.58) D more hyperopia than the monocular device. Under cycloplegia, this difference decreased to +0.26 D (+0.99, −0.48) D. Both autorefractors provided higher hyperopia with cycloplegia, with differences inversely correlated with age (r = −0.4; p < 0.05). Conclusions: Whenever possible, refraction in young hyperopes should be measured under cycloplegic conditions using a binocular open-field autorefractor to promote greater accommodative relaxation and ensure more reliable hyperopia measurements in both clinical practice and research. Full article