Search Results (53)

Fabry disease (FD) is an X-linked systemic lysosomal storage disease caused by mutations in the galactosidase-α (GLA) gene, which encodes the α-galactosidase A (α-AGAL) enzyme. FD can lead to serious complications, including early death, if left untreated. For over 20 years, enzyme replacement therapy (ERT) based on the use of agalsidase-α and agalsidase-β has been the standard treatment for FD, alongside new molecules that have enriched the therapeutic armamentarium and others that are being tested to expand it further. Unfortunately, ERT can be associated with the formation of inhibiting antidrug antibodies (ADAs), which impact ERT clinical efficacy and have consequences affecting safety and therapeutic adherence. A group of FD specialists discussed the problem of immunogenicity in FD, analyzing the most recent literature and the strategies that are currently being used to address it. Once formed, fluctuating levels of ADAs persist and have an impact on the clinical picture and prognosis of the disease that is still the subject of lively scientific debate. The critical nature of ADAs is demonstrated by their ability to bind to the enzyme, increasing drug clearance while forming immune complexes that can build up in the tissues causing chronic inflammation that aggravates the progression of the disease and affects the onset of acute reactions after the infusion, impacting therapeutic adherence. Although similar in their therapeutic mechanism, agalsidase-α and agalsidase-β differ in their production process, with resulting differences from a pharmacokinetic and pharmacodynamic point of view and diverse immunological implications: despite showing rather overlapping efficacy outcomes, agalsidase-α demonstrates a better tolerability profile, with a lower frequency of ADAs, than agalsidase-β. Given the extreme variability of the clinical picture, it is crucial for optimal FD management that the most appropriate molecule is chosen by taking into account the unique immunological risk profile of each single patient, and particular attention should be paid to naïve subjects by periodic measurement of ADAs during therapy and cross-referencing data to correlate serological and clinical patterns. Full article

Selective catalytic reduction (SCR) of NO using various reducing agents is a critical area of research for mitigating environmental pollution. In this study, the influence of active phase loading was investigated in four bimetallic Pt-Ag/Al₂O₃-WO_x catalysts, one monometallic Ag/Al₂O₃-WO_x catalyst, and one Pt-Ag/Al₂O₃-WO_x catalyst subjected to high-severity air-SO₂ pretreatment. All catalysts were supported on cordierite monoliths, and their performance in NO SCR was evaluated using H₂, C₃H₈, and CO as reducing agents. An increase in the active phase loading (Pt-Ag/Al₂O₃) from 10.7 wt% to 17.4 wt% resulted in higher conversions of NO, C₃H₈, and H₂, as well as improved N₂ selectivity. However, CO conversion decreased as the active phase loading increased, which was attributed to competitive reduction by H₂, since both reactions occur within the same temperature range (100–200 °C). The presence of N₂O below 6 ppm was observed in some catalysts. Furthermore, higher active phase loadings led to increased carbon deposition; the Ag/Al₂O₃-WO_x catalyst exhibited the highest carbon content (5 wt%). The deposited carbon was identified as ordered graphitic carbon. In the Pt-Ag catalysts, the presence of Ag⁺ and Agⁿδ⁺ species, as well as the Ag° plasmon, was identified by UV-Vis spectroscopy. STEM analysis showed Ag-Pt crystallites with an average size of 24 nm, which may have contributed to the higher NO conversion observed at 350 °C and the improved N₂ selectivity at 100 °C in the Pt-Ag bimetal catalysts, compared to the activity of the Ag/Al₂O₃-WOx catalyst. Full article

In this work, we investigate the electrical properties of a metal–insulator–semiconductor (MIS) heterojunction based on porous silicon dioxide (Ag/pSiO₂/Si). The porous silicon (PS) films were elaborated by electrochemical anodization under specific experimental conditions to obtain a porosity of about 55%. Porous silicon (PS) was oxidized by IR-RTP at different oxidation temperatures (Tox) ranging from 200 to 950 °C under an oxygen atmosphere. The morphology of the samples was analyzed using a scanning electron microscope (SEM). Ag/Al and Ag contacts were screen printed on the back and front sides of the heterojunction, respectively. Both the series and shunt resistances were derived from dark current–voltage (I–V) characteristics related to the various Ag/pSiO₂/Si heterojunctions. In this context, the reflectance was also measured at different oxidation temperatures to investigate its correlation with the series resistance (Rs) and shunt resistance (Rsh). The optimum electrical performance was obtained for an oxidation temperature close to 400 °C. Depending on the pSiO₂ thickness, two conduction mechanisms were highlighted within the devices. For a Tox below 200 °C, as well as for the non-oxidized devices, the conduction mechanism is governed by the tunneling current through the pSiO₂ film. However, when the Tox increases and exceeds 200 °C, the pSiO₂ thickness increases, leading to the switching of the conduction mechanism to a thermionic instead of a tunneling effect mechanism. Full article

Fabry disease is a rare genetic disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A (AGAL), resulting in the accumulation of globotriaosylceramides (Gb3) in tissues and organs. This buildup leads to progressive, multi-systemic complications that severely impact quality of life and can be life-threatening. Interpreting the functional consequences of missense variants in the GLA gene remains a significant challenge, especially in rare diseases where experimental evidence is scarce. In this study, we present an integrative computational framework that combines structural, interaction, pathogenicity, and stability data from both in silico tools and experimental sources, enriched through expert curation and structural analysis. Given the clinical relevance of pharmacological chaperones in Fabry disease, we focus in particular on the structural characteristics of variants classified as “amenable” to such treatments. Our multidimensional analysis—using tools such as AlphaMissense, EVE, FoldX, and ChimeraX—identifies key molecular features that distinguish amenable from non-amenable variants. We find that amenable mutations tend to preserve protein stability, while non-amenable ones are associated with structural destabilisation. By comparing AlphaMissense with alternative predictors rooted in evolutionary (EVE) and thermodynamic (FoldX) models, we explore the relative contribution of different biological paradigms to variant classification. Additionally, the investigation of outlier variants—where AlphaMissense predictions diverge from clinical annotations—highlights candidates for further experimental validation. These findings demonstrate how combining structural bioinformatics with machine learning–based predictions can improve missense variant interpretation and support precision medicine in rare genetic disorders. Full article

Non-radiative decay of surface plasmon (SP) offers a novel paradigm for efficient conversion of photons into carriers. However, the narrow bandwidth of SP has been a significant obstacle to the widespread applications. Previously, research and applications mainly focused on noble metals such as Au, Ag, and Cu. In this article, we report an Ag-Al alloy material, μ-Ag₃Al, in which the surface plasmon operating bandwidth is 1.7 times that of Ag and hot carrier transport properties are comparable with those of AuAl. The results show that μ-Ag₃Al allows efficient direct interband electronic transitions from ultraviolet (UV) to near infrared range. Spherical nanoparticles of μ-Ag₃Al exhibit the localized surface plasmon resonance (LSPR) effect in the ultraviolet region. Its surface plasmon polariton (SPP) shows strong non-radiative decay at 3.36 eV, which is favorable for the generation of high-energy hot carriers. In addition, the penetration depth of SPP in μ-Ag₃Al remains high across the UV to the near-infrared range. Moreover, the transport properties of hot carriers in μ-Ag₃Al are comparable with those in Al, borophene and Au-Al intermetallic compounds. These properties can provide guidance for the design of plasmon-based photodetectors, solar cells, and photocatalytic reactors. Full article

Diesel particulate matter (DPM) represents a deleterious environmental contaminant that necessitates the development of effective catalytic oxidation methodologies. This research delineates a comparative analysis of silver-supported metal oxide catalysts (Ag/Al₂O₃, Ag/TiO₂, Ag/ZnO, and Ag/CeO₂), with an emphasis on the effects of silver distribution and the metal-support interaction on the oxidation of DPM. An array of characterization techniques including XRD, HRTEM, XPS, H₂-TPR, TEM, GC-MS, TGA, and in situ DRIFTS was employed. The novelty of this study resides in elucidating the oxidation mechanism through a tripartite pathway and recognizing Ag⁰ as the predominant active species involved in soot oxidation. The Ag/Al₂O₃ catalyst demonstrated superior catalytic performance, achieving a reduction in the ignition temperature by more than 50 °C, attributable to the optimal dispersion of Ag nanoparticles and a balanced metal-support interaction. Conversely, an excessive interaction observed in Ag/ZnO resulted in diminished catalytic activity. The oxidation of DPM transpires through the volatilization of VOCs (<300 °C), the oxidation by reactive oxygen species, and the combustion of soot (>300 °C). This investigation offers significant contributions to the formulation of highly efficient silver-based catalysts for emissions control, with a particular focus on optimizing Ag dispersion and support interactions to enhance catalytic efficacy. Full article

This study shows how important the coordination of Al³⁺ ions in the silver support is for the overall activity in soot combustion. Five silver catalysts with a silver content of 14.7 wt.% were prepared using the following supports: α-Al₂O₃, which has only octahedrally coordinated Al³⁺, θ-Al₂O₃, which has both octahedrally and tetrahedrally coordinated Al³⁺, and zeolites, which contain only tetrahedrally coordinated Al³⁺: 10X, 13X, and 5A. The analysis of the diffraction patterns showed that silver on the surface of catalysts made with the first four supports was mainly in the metallic form, except for Ag/5A in which there was a lack of reflections from Ag⁰ in the XRD pattern. Nevertheless, the difference in the activity of the support and the catalyst as well as the EDX results indicate the presence of silver on the catalyst. The SEM-EDX analysis showed that the silver dispersion strongly depends on the support and that even the zeolites with large silver particles on the surface have silver evenly distributed across the surface. The activity of the catalysts decreased in the following series: Ag/Al 1200 > Ag/5A ≈ Ag/13X > Ag/10X ≈ Ag/Al 550. Time-of-Flight Secondary Ion Mass Spectrometry was used to delve into the reason why the catalyst with the low-surface area α-Al₂O₃ support yielded a better catalyst than that obtained using the high-surface area alumina support and showed that different ratios of secondary ions were emitted from the two surfaces. Full article

Background: The COVID-19 pandemic has led to widespread long-term complications, known as post-COVID conditions (PCC), particularly affecting vulnerable populations such as cancer patients. This study aims to predict the incidence of PCC in hospitalised cancer patients using the data from a longitudinal cohort study conducted in four major university hospitals in Moscow, Russia. Methods: Clinical data have been collected during the acute phase and follow-ups at 6 and 12 months post-discharge. A total of 49 clinical features were evaluated, and machine learning classifiers including logistic regression, random forest, support vector machine (SVM), k-nearest neighbours (KNN), and neural network were applied to predict PCC. Results: Model performance was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. KNN demonstrated the highest predictive performance, with an AUC of 0.80, sensitivity of 0.73, and specificity of 0.69. Severe COVID-19 and pre-existing comorbidities were significant predictors of PCC. Conclusions: Machine learning models, particularly KNN, showed some promise in predicting PCC in cancer patients, offering the potential for early intervention and personalised care. These findings emphasise the importance of long-term monitoring for cancer patients recovering from COVID-19 to mitigate PCC impact. Full article

Solid-state lithium batteries are considered ideal due to the safety of solid-state electrolytes. The Na superionic conductor-type Li_1.3Al_0.3Ti_1.7(PO₄)₃ (LATP) is a solid electrolyte with high ionic conductivity, low cost, and stability. However, LATP is reduced upon contact with metallic lithium, leading to lithium dendrite growth on the anode during charging. In this study, LATP was synthesized, and the relationship between crystallinity and ionic conductivity was investigated at different heat treatment temperatures. Optimal sintering conditions and ionic conductivity were analyzed for sintering temperatures from 800 to 1000 °C. To suppress reactions with Li metal, 50 nm thick Ag and 10 nm thick Al₂O₃ layers were deposited on LATP via DC sputtering and plasma-enhanced atomic layer deposition. The electrochemical stability was tested under three conditions: uncoated LATP, Al₂O₃-coated LATP, and Ag+Al₂O₃-coated LATP. The stability improved in the following order: uncoated < Al₂O₃-coated < Ag+Al₂O₃-coated. The Al₂O₃ coating suppressed secondary phase formation by preventing direct contact between LATP and Li, while Ag coating mitigated charge concentration, inhibiting dendrite growth. These findings demonstrate that Ag and Al₂O₃ nano-layers enhance electrolyte stability, advancing solid-state battery reliability and commercialization. Full article

Plasmonic applications have traditionally relied on noble metals such as gold (Au) and silver (Ag) for their excellent plasmonic performance in the visible and near-infrared spectrum. However, these metals are costly, scarce, and have limitations such as low stability (Ag) and interband transition losses, which restrict their spectral range. To address these issues, alternative plasmonic materials have been explored. One such material is aluminum (Al), which is inexpensive, abundant, and exhibits remarkable plasmonic properties in the UV region as well as wide tunability. Al is also compatible with complementary metal–oxide semiconductor (CMOS) fabrication processes and is very stable due to its ultrathin native oxide layer. Alloying different metals can combine their advantageous properties, resulting in enhanced tunable optical characteristics. This study investigates the LSPR properties of AgAl alloy nanoparticles grown after the annealing of precursor AgAl bilayer films. Interestingly, LSPRs were also observed in some cases for the as-deposited bilayers. The experimental results were complemented with simulations conducted via the rigorous coupled-wave analysis (RCWA) method. The investigated materials could be potentially useful for applications in energy harvesting or color printing. Full article

Background: Fabry disease is a progressive, X chromosome-linked lysosomal storage disorder with multiple organ dysfunction. Due to the absence or reduced activity of alpha-galactosidase A (AGAL), glycosphingolipids, primarily globotriaosyl-ceramide (Gb3), concentrate in cells. In heterozygous women, symptomatology is heterogenous and currently routinely used fluorometry-based assays measuring mean activity mostly fail to uncover AGAL dysfunction. The aim was the development of a flow cytometry assay to measure AGAL activity in individual cells. Methods: Conventional and multispectral imaging flow cytometry was used to detect AGAL activity. Specificity was validated using the GLA knockout (KO) Jurkat cell line and AGAL inhibitor 1-deoxygalactonojirimycin. The GLA KO cell line was generated via CRISPR-Cas9-based transfection, validated with exome sequencing, gene expression and substrate accumulation. Results: Flow cytometric detection of specific AGAL activity is feasible with fluorescently labelled Gb3. In the case of Jurkat cells, a substrate concentration of 2.83 nmol/mL and 6 h of incubation are required. Quenching of the aspecific exofacial binding of Gb3 with 20% trypan blue solution is necessary for the specific detection of lysosomal substrate accumulation. Conclusion: A flow cytometry-based assay was developed for the quantitative detection of AGAL activity at the single-cell level, which may contribute to the diagnosis of Fabry patients. Full article

Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs such as the kidneys, heart, and nervous system. While FD was initially considered predominantly affecting males, recent studies have uncovered that heterozygous Fabry women, carrying a single mutated GLA gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers. The mechanisms underlying the diverse clinical manifestations in females remain not fully understood due to X-chromosome inactivation (XCI). XCI also known as “lyonization”, involves the random inactivation of one of the two X chromosomes. This process is considered a potential factor influencing phenotypic variation. This review delves into the complex landscape of FD in women, discussing its genetic basis, the available biomarkers, clinical manifestations, and the potential impact of XCI on disease severity. Additionally, it highlights the challenges faced by heterozygous Fabry women, both in terms of their disease burden and interactions with healthcare professionals. Current treatment options, including enzyme replacement therapy, are discussed, along with the need for healthcare providers to be well-informed about FD in women, ultimately contributing to improved patient care and quality of life. Full article

Globularia alypum L. (GA) belonging to the Globulariaceae family is a Mediterranean plant which is widely used in traditional Tunisian medicine. The aim of this study was to investigate the phytochemical composition, antioxidant, anti-arthritic, antiproliferative, antibacterial and antibiofilm potential of aqueous GA leaf extracts (AGAL). Quantitative analyses of the different constituents of extracts were evaluated by high-performance liquid chromatography with photodiode-array detection (HPLC-DAD). Spectrophotometric methods and chemical tests were used for antioxidant and anti-arthritic activities. The antiproliferative study was evaluated using colorectal cancer SW620 cells, while the antibacterial assessment and analysis of the antibiofilm effects were determined by the microdilution method and the crystal violet assay, respectively. AGAL extracts presented several components, mainly Nepetin-7-Glucoside and trans-ferrulic acid. The results showed that they had an important antioxidant (IC₅₀ = 0.34; 0.38 and 1.20 mg/mL) and anti-arthritic (IC₅₀ = 2.94 mg/mL) properties, and these effects are displayed in a dose-dependent manner. In addition, this extract demonstrated significant antiproliferative (IC₅₀ = 50 µg/mL), antibacterial (MIC = 6.25 mg/mL and MBC = 6.25 mg/mL), and antibiofilm (59.70% at 25 mg/mL) properties especially against S. aureus. The results achieved confirm the important role of this plant as a source of therapeutic activities. Full article

The phase equilibria of the Ag-Al-Au ternary system and the solid-state reaction couple for the Au-xAg/Al system were investigated isothermally at 450 °C. By investigating the Ag-Al-Au ternary system and its isothermal section, this study aims to provide a clearer understanding of the phase stability and interfacial reactions between different phases. This information is crucial for designing materials and processes in electronic packaging, with the potential to reduce costs and improve reliability. There were seven single-phase regions, thirteen two-phase regions, and six three-phase regions, with no ternary intermetallic compound (IMC) formed in the isothermal section of the Ag-Al-Au ternary system. When the Au-25 wt.% Ag/Al couple was aged at 450 °C for 240–1500 h, the AuAl₂, Au₂Al, and Au₄Al phases formed at the interface. When the Ag contents increased to 50 and 75 wt.%, the Ag₂Al, AuAl₂, and Au₄Al phases formed at the interface. When the aging time increased from 240 h to 1500 h, the total IMC thickness in all Au-xAg/Al couples became thicker, but the types of IMCs formed at the interface did not change. The total IMC thickness also increased with the increase in the Ag content. When the Ag content was greater than 25 wt.%, the Au₂Al phase was converted into the Ag₂Al phase. The IMC growth mechanism in all of the couples followed a reaction-controlled process. Full article

The aim of this study is to comprehensively examine the structural composition and properties of the AgAlS₂ crystal during its high-pressure phase. This analysis delves into the second coordination environment of the crystal structure and elucidates the distinct transformations it undergoes during the phase transition. The band energy structure was calculated, and the origin of electronic levels was clarified. It is shown that the crystal becomes non-stratified during the phase transition. This study also determined the values of the crystal’s carrier effective masses, underscoring its spatial anisotropy. It was found that the calculated optical functions are similar to the crystal in the chalcopyrite structure, and their differences are shown. Further, this study involved the calculation of the crystal’s phonon spectrum, revealing the spectrum’s transformation during the phase transition. The vibrational frequencies were also obtained, with a symmetrical classification of vibrational modes. Finally, this study derived the infrared and Raman spectra of the AgAlS₂ crystal, thereby providing a comprehensive picture of the crystal during its high-pressure phase. Full article