Search Results (31)

Fungal infection caused by invasive Aspergillus is a life-threatening complication in immunocompromised pediatric cancer patients. However, the early diagnosis of invasive infection remains a clinical challenge due to the lack of specific, non-invasive biomarkers. The current study investigates plasma metabolomic profiling integrated with an AI-derived fungal secondary metabolite database to identify potential biomarkers for rapid, non-invasive detection of Aspergillus infection. Plasma samples from thirteen pediatric oncology patients were analyzed using untargeted metabolomics based on UHPLC-MS/MS. Based on galactomannan assay results, three patients were classified as Aspergillus-Infected (AIC) and ten as non-infected controls (NPCs). An in-house custom database for secondary metabolites of fungi was incorporated to enhance metabolite annotation. Eight metabolites were found to be candidate biomarkers based on statistical significance, fold change, and biological relevance. In the AIC cohort, aflatoxin B1, aspergillimide, fumifungin, and uridine were found to be significantly elevated while citric acid presented a decrease. Multivariate analysis utilizing PCA and PLSDA showed distinct group separation. Moreover, sample size estimation indicates that a minimum of 25 participants would be needed in future studies for appropriate statistical power. Full article

Microgrid systems face challenges in preserving frequency stability due to the fluctuating nature of renewable energy sources (RESs), underscoring the importance of advanced frequency stabilization strategies. To ensure power system stability in situations where renewable energy significantly contributes to the energy mix, it is essential to implement load frequency controllers (LFCs). Moreover, with the widespread use of electric vehicles (EVs), leveraging battery storage from EVs for microgrid frequency control is becoming increasingly crucial. This integration enhances grid stability and offers a sustainable solution by utilizing renewable energy more efficiently and reducing dependency on traditional power sources. Therefore, this paper proposes an innovative approach to LFCs, using fractional-order control techniques to boost the resilience of the interconnected microgrid systems. The approach centers on a centralized control scheme with a tilt fractional-order integral-derivative featuring an accelerated derivative (TFOID-Accelerated) controller. The accelerated derivative component of this controller is tailored to mitigate high-frequency disturbances, while its tilt feature and fractional integration effectively handle disturbances at lower frequencies. As a result, the proposed controller is expected to efficiently counteract disturbances caused by variability in RESs and/or load changes, achieving a high level of disturbance rejection. Additionally, this paper employs the recent growth optimizer (GO) method for the optimal design of the controller’s parameter set, avoiding the need for complex control theories, elaborate disturbance observers, filters, and precise power system modeling. The GO algorithm enhances fractional-order capabilities, offering a robust solution to the challenges of renewable energy variability and demand fluctuations. This is accomplished by optimizing parameters and simplifying the control system design across different microgrid scenarios. The proposed TFOID-Accelerated LFC demonstrates superior performance in enhancing frequency stability and minimizing oscillations compared to existing controllers, including traditional proportional-integral-derivative (PID), PID-Accelerated (PIDA), and tilt-integral-derivative (TID) controllers. Full article

This study provides a comprehensive computational exploration of the inhibitory activity and metabolic pathways of 8-methoxypsoralen (8-MP), a furocoumarin derivative used for treating various skin disorders, on cytochrome P450 (P450). Employing quantum chemical DFT calculations, molecular docking, and molecular dynamics (MD) simulations analyses, the biotransformation mechanisms and the active site binding profile of 8-MP in CYP1B1 were investigated. Three plausible inactivation mechanisms were minutely scrutinized. Further analysis explored the formation of reactive metabolites in subsequent P450 metabolic processes, including covalent adduct formation through nucleophilic addition to the epoxide, 8-MP epoxide hydrolysis, and non-CYP-catalyzed epoxide ring opening. Special attention was paid to the catalytic effect of residue Phe268 on the mechanism-based inactivation (MBI) of P450 by 8-MP. Energetic profiles and facilitating conditions revealed a slight preference for the C4′=C5′ epoxidation pathway, while recognizing a potential kinetic competition with the 8-OMe demethylation pathway due to comparable energy demands. The formation of covalent adducts via nucleophilic addition, particularly by phenylalanine, and the generation of potentially harmful reactive metabolites through autocatalyzed ring cleavage are likely to contribute significantly to P450 metabolism of 8-MP. Our findings highlight the key role of Phe268 in retaining 8-MP within the active site of CYP1B1, thereby facilitating initial oxygen addition transition states. This research offers crucial molecular-level insights that may guide the early stages of drug discovery and risk assessment related to the use of 8-MP. Full article

Although primary open-angle glaucoma (POAG) is a major cause of blindness worldwide, patients’ immune response and its relation to the disease course have not been fully unraveled in terms of analyses of circulating B-cell subsets, as well as the association of these subsets with the severity of POAG clinical features. Subjects and Methods: Flow cytometry was used to determine B-cell subset frequencies from 30 POAG patients grouped by hierarchical cluster analysis or the mean deviation (MD) of the visual field (VF) and correlated with the patients’ clinical and pathological data, as well as with BSF-2(IL-6) and CSIF:TGIF(IL-10), which were quantified in peripheral blood samples of patients and controls by ELISA. Results: The total B-cell frequency was increased in the POAG group in comparison to the control group (n = 30). Frequencies of specific B-cell subsets, such as double-negative (DN) and naïve B-cell subsets, were increased in relation to the severity of the POAG disease. However, the unswitched memory B compartment subset decreased in the POAG group. Other non-typical B-cell subsets such as DN B cells also showed significant changes according to the POAG disease severity course. These differences allow us to identify POAG severity-associated inflammatory clusters in patients with specifically altered B-cell subsets. Finally, ocular parameters, biomarkers of inflammation, and other glaucoma-related or non-clinical scores exhibited correlations with some of these B-cell subpopulations. Conclusion: The severity of the POAG disease course is accompanied by changes in the B-cell subpopulation, namely, DN B cells. Furthermore, the existing relationship of the B-cell subset frequencies with the clinical and the inflammatory parameters BSF-2(IL-6), CSIF:TGIF(IL-10), and the BSF-2(IL-6) to CSIF:TGIF(IL-10) ratio suggests that these B lymphocyte cells could serve as potential molecular bio-markers for assessing POAG disease severity and/or progression. Full article

Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients. Full article

This study comprehensively investigates the impact of various parameters on aluminum matrix composites (AMCs) fabricated using the powder metallurgy (PM) technique. An Al-Cu matrix composite (2xxx series) was employed in the current study, and Al₂O₃ was used as a reinforcement. The performance evaluation of the Al-4Cu/Al₂O₃ composite involved analyzing the influence of the Al₂O₃ weight percent (wt. %), the height-to-diameter ratio (H/D) of the compacted samples, and the compaction pressure. Different concentrations of the Al₂O₃ reinforcement, namely 0%, 2.5%, 5.0%, 7.5%, and 10% by weight, were utilized, while the compaction process was conducted for one hour under varying pressures of 500, 600, 700, 800, and 900 MPa. The compacted Al-4Cu/Al₂O₃ composites were in the form of cylindrical discs with a fixed diameter of 20 mm and varying H/D ratios of 0.75, 1.0, 1.25, 1.5, and 2.0. Moreover, the machine learning (ML), design of experiment (DOE), response surface methodology (RSM), genetic algorithm (GA), and hybrid DOE-GA methodologies were utilized to thoroughly investigate the physical properties, such as the relative density (RD), as well as the mechanical properties, including the hardness distribution, fracture strain, yield strength, and compression strength. Subsequently, different statistical analysis approaches, including analysis of variance (ANOVA), 3D response surface plots, and ML approaches, were employed to predict the output responses and optimize the input variables. The optimal combination of variables that demonstrated significant improvements in the RD, fracture strain, hardness distribution, yield strength, and compression strength of the Al-4Cu/Al₂O₃ composite was determined using the RSM, GA, and hybrid DOE-GA approaches. Furthermore, the ML and RSM models were validated, and their accuracy was evaluated and compared, revealing close agreement with the experimental results. Full article

Viruses can trigger glomerulonephritis (GN) development. Hepatitis viruses, especially Hepatitis C virus and Hepatitis B viruses, are examples of the viruses that trigger GN initiation or progression. However, the proof of a correlation between GN and Hepatitis E virus infection is not clear. Some studies confirmed the development of GN during acute or chronic HEV infections, mainly caused by genotype 3. While others reported that there is no relation between HEV exposure and GN development. A recent study showed that a reduced glomerular filtration rate was developed in 16% of acute HEV genotype 1 (HEV-1) infections that returned to normal during recovery. HEV-1 is endemic in Egypt with a high seroprevalence among villagers and pregnant women. There is no available data about a link between HEV and GN in Egypt. Methods: GN patients (n = 43) and matched healthy subjects (n = 36) enrolled in Assiut University hospitals were included in this study. Blood samples were screened for hepatotropic pathogens. Tests for HEV markers such as HEV RNA and anti-HEV antibodies (IgM and IgG) were performed. Laboratory parameters were compared in HEV-seropositive and HEV-seronegative GN patients. Results: Anti-HEV IgG was detected in 26 (60.5%) out of 43 GN patients. HEV seroprevalence was significantly higher in GN than in healthy controls, suggesting that HEV exposure is a risk factor for GN development. None of the GN patients nor the healthy subjects were positive for anti-HEV IgM or HEV RNA. There was no significant difference between seropositive and seronegative GN patients in terms of age, gender, albumin, kidney function profiles, or liver transaminases. However, anti-HEV IgG positive GN patients had higher bilirubin levels than anti-HEV IgG negative GN patients. HEV-seropositive GN patients had a significantly elevated AST level compared to HEV-seropositive healthy subjects. Conclusion: exposure to HEV infection could be complicated by the development of GN. Full article

Commercial pure Mg specimens were processed through equal channel angular pressing (ECAP) using two dies with die angles of 90° and 120°. Mg billets were processed up to four passes via different route types. Machine learning (ML) techniques were adopted to estimate the ECAP parameters and verify the experimental findings. Several ML techniques were employed to estimate the effect ECAP parameters of pure Mg on microstructural evolution, Vicker’s microhardness (HV), and tensile properties for ECAP billets and their as-annealed (AA) counterparts. Electron back-scatter diffraction (EBSD) was applied to determine the structural evolution and crystallographic texture both prior to and following the ECAP process for the Mg billets. EBSD analysis showed that route Bc is the most effective route in grain refinement, and four passes of route Bc experienced a significant refinement of 86% compared to the AA condition. Furthermore, the crystallographic texture showed that four passes of route Bc produced the most robust texture that was greater than 26.21 times random. ML findings revealed that the grain size demonstrated a strong correlation of −0.67 with rising number of passes, while ϕ affected the grain size strongly with 0.83. When adopting a 90°-die to accumulate the plastic strain up to 4Bc, the subsequent HV was indeed 111% higher than that of the AA equivalent. From ML findings it was clear that the number of passes was the most significant parameter on the Mg HV values, while ECAP channel angle (ϕ) revealed high correlation factor with HV values as well. Furthermore, four passes of route Bc with ϕ = 90° and 120° led to a significant increase of the tensile strength by 44.7%% and 35.7%, respectively, compared to the AA counterpart. ML findings revealed that the tensile strength was affected by the increasing number of passes with a strong correlation of 0.81, while affecting ductility moderately with 0.47. Full article

Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m². AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients’ age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections. Full article

Understanding the functioning of shrub species during dry periods is necessary to forecast ecosystem responses to future climates, particularly in Mediterranean environments. We evaluated the seasonal changes in leaf gas exchange, hydraulic traits, carbon and nitrogen isotopes, and non-structural carbohydrates of seeders and resprouting shrub species typical of Aleppo pine forests across an aridity gradient in Tunisia: Djebel Zaghouan (subhumid climate), Djebel Mansour (semiarid transitional climate), and Djebel El Sarj (semi-arid climate). We monitored seven woody species: Pistacia lentiscus, Erica multiflora, Phillyrea latifolia (resprouters), Cistus monspeliensis, Rosmarinus officinalis (seeders), Globularia alypum, and Calicotome villosa (resprouters-seeders). The seasonal variation in leaf water content was usually higher in seeders than in resprouters and was associated with higher resistance to embolism. In contrast, the seasonal variation in non-structural carbohydrates was higher in resprouters, especially at the driest site. Both δ¹³C and δ¹⁵N displayed seasonal enrichment-depletion patterns, with seeders showing an overall higher δ¹³C in summer than in spring, consistent with a water-saving strategy of increasing water use efficiency. Discriminant analysis suggested that resprouters can sustain a positive carbon balance during drought periods. The differential impact of summer droughts on water status and the ecophysiology of these plant strategies may lead to different ecosystem dynamics depending on whether climate change tips the balance towards a preponderance of stressors (drought) or disturbances (fire) in dry Mediterranean areas. Full article

Several physics-based models have been utilized in material design for the simulation and prediction of material properties. In this study, several machine-learning (ML) approaches were used to construct a prediction model to analyze the influence of equal-channel angular pressing (ECAP) parameters on the microstructural, corrosion and mechanical behavior of the biodegradable magnesium alloy ZK30. The ML approaches employed were linear regression, the Gaussian process, and support vector regression. For the optimization of the alloy’s performance, experiments were conducted on ZK30 billets using different ECAP routes, channel angles, and number of passes. The adopted ML model is an adequate predictive model which agreed with the experimental results. ECAP die angles had an insignificant effect on grain refinement, compared to the route type. ECAP via four passes of route Bc (rotating the sample 90° on its longitudinal axis after each pass in the same direction) was the most effective condition producing homogenous ultrafine grain distribution of 1.92 µm. Processing via 4-Bc and 90° die angle produced the highest hardness (97-HV) coupled with the highest tensile strength (344 MPa). The optimum corrosion rate of 0.140 mils penetration per year (mpy) and the optimum corrosion resistance of 1101 Ω·cm² resulted from processing through 1-pass using the 120°-die. Grain refinement resulted in reducing the corrosion rates and increased corrosion resistance, which agreed with the ML findings. Full article

Clade 2.3.4.4 H5Nx influenza viruses have further diversified into several subclades. Sub-clade 2.3.4.4b H5N1 viruses have been widely circulating in wild birds and detected in Europe, Africa, Asia, and North America since October 2020. In this study, we report the first detection of highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses in wild birds and domestic ducks from live bird markets in Egypt. Phylogenetic analysis revealed that the Egyptian H5N1 virus retained the genomic composition of Eurasian strains. Mutations in the viral proteins associated with zoonotic potential and pathogenicity were detected in Egyptian isolates. Egypt is considered a hot spot for the evolution of the influenza virus, so active surveillance of avian influenza viruses in Egypt is warranted. Full article

Copper and its related alloys are frequently adopted in contemporary industry due to their outstanding properties, which include mechanical, electrical, and electronic applications. Equal channel angular pressing (ECAP) is a novel method for producing ultrafine-grained or nanomaterials. Modeling material design processes provides exceptionally efficient techniques for minimizing the efforts and time spent on experimental work to manufacture Cu or its associated alloys through the ECAP process. Although there have been various physical-based models, they are frequently coupled with several restrictions and still require significant time and effort to calibrate and enhance their accuracies. Machine learning (ML) techniques that rely primarily on data-driven models are a viable alternative modeling approach that has recently achieved breakthrough achievements. Several ML algorithms were used in the modeling training and testing phases of this work to imitate the influence of ECAP processing parameters on the mechanical and electrical characteristics of pure Cu, including the number of passes (N), ECAP die angle (φ), processing temperature, and route type. Several experiments were conducted on pure commercial Cu while altering the ECAP processing parameters settings. Linear regression, regression trees, ensembles of regression trees, the Gaussian process, support vector regression, and artificial neural networks are the ML algorithms used in this study. Model predictive performance was assessed using metrics such as root-mean-squared errors and R² scores. The methodologies presented here demonstrated that they could be effectively used to reduce experimental effort and time by reducing the number of experiments runs required to optimize the material attributes aimed at modeling the ECAP conditions for the following performance characteristics: impact toughness (I_T), electrical conductivity (E_C), hardness, and tensile characteristics of yield strength (σ_y), ultimate tensile strength (σ_u), and ductility (D_u) Full article

Lipopolysaccharide (LPS) proved to be an important tool, not only in the induction of neuroinflammatory models, but also in demonstrating the behavioral and cognitive consequences of endotoxemia. Curcumin, in its native form, has proven to be a worthy candidate for further development as it protects the dopaminergic neurons against LPS-induced neurotoxicity. However, it remains hindered by its poor bioavailability. In this study we aim to explore the possible molecular mechanism of LPS-induced neurotoxicity and the possible protective effects of orally supplemented nanocurcumin. Thirty-six adult male Wistar rats weighing 170–175 g were divided into six groups and treated with single I.P. (intra-peritoneal) dose of LPS (sigma and extracted; separately) (5 mg/kg BW) plus daily oral nanocurcumin (15 mg/kg BW). The rats were followed for 7 days after the LPS injection and nanocurcumin supplementations daily via oral gavage. After scarification, the levels of neurotransmitters, antioxidants, and amyloidogenesis markers were assessed in brain tissues. Nanocurcumin showed adequate antioxidant and neuroprotective effects, rescuing the rats which had been injected intraperitoneally with LPS endotoxin. Full article