Search Results (2,884)

Despite targeting mainly the respiratory tract, SARS-CoV-2 disrupts T cell homeostasis in ways that may explain both acute lethality and long-term immunological consequences. In this study, we aimed to evaluate the T-cell-mediated chain of immunity and formation of TCR via TREC assessment in COVID-19 and long COVID (LC). For this study, we collected 231 blood samples taken from patients with acute COVID-19 (n = 71), convalescents (n = 51), people diagnosed with LC (n = 63), and healthy volunteers (n = 46). With flow cytometry, we assessed levels of CD4+ and CD8+ minor T cell subpopulations (i.e., naïve, central and effector memory cells (CM and EM), Th1, Th2, Th17, Tfh, Tc1, Tc2, Tc17, Tc17.1, and subpopulations of effector cells (pE1, pE2, effector cells)). Additionally, we measured TREC levels. We found distinct changes in immune cell distribution—whilst distribution of major subpopulations of T cells was similar between cohorts, we noted that COVID-19 was associated with a decrease in naïve Th and CTLs, an increase in Th2/Tc2 lymphocyte polarization, an increase in CM cells, and a decrease in effector memory cells 1,3, and TEMRA cells. LC was associated with naïve CTL increase, polarization towards Th2 population, and a decrease in Tc1, Tc2, Em2, 3, 4 cells. We also noted TREC correlating with naïve cells subpopulations. Our findings suggest ongoing immune dysregulation, possibly driven by persistent antigen exposure or tissue migration of effector cells. The positive correlation between TREC levels and naïve T cells in LC patients points to residual thymic activity. The observed Th2/Th17 bias supports the hypothesis that LC involves autoimmune mechanisms, potentially driven by molecular mimicry or loss of immune tolerance. Full article

A novel strategy has been developed for extracting value-added resources from iron-lean, high-alumina- and -silica-containing red muds (RMs). With little or no recycling, such RMs are generally destined for waste dumps. Detailed results are presented on the carbothermic reduction of 100% RM (29.3 wt.% Fe₂O₃, 22.2 wt.% Al₂O₃, 20.0 wt.% SiO₂, 1.2 wt.% CaO, 12.2 wt.% Na₂O) and its 2:1 blends with Fe₂O₃ and red mill scale (MS). Synthetic graphite was used as the reductant. Carbothermic reduction of RM and blends was carried out in a Tamman resistance furnace at 1650 °C for 20 min in an Ar atmosphere. Reduction residues were characterized using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), elemental mapping and X-ray diffraction (XRD). Small amounts of Fe₃Si alloys, alumina, SiC and other oxide-based residuals were detected in the carbothermic residue of 100% RM. A number of large metallic droplets of Fe–Si alloys were observed for RM/Fe₂O₃ blends; no aluminium was detected in these metallic droplets. A clear segregation of alumina was observed as a separate phase. For the RM/red MS blends, a number of metallic Fe–Si droplets were seen embedded in an alumina matrix in the form of a cermet. This study has shown the regeneration of alumina and the formation of alumina-based cermets, Fe–Si alloys and SiC during carbothermic reduction of RM and its blends. This innovative recycling strategy could be used for extracting value-added resources from iron-lean RMs, thereby enhancing process productivity, cost-effectiveness of alumina regeneration, waste utilization and sustainable developments in the field. Full article

Phase separation processes facilitate the formation of membrane-less organelles and involve interactions within structured domains and intrinsically disordered regions (IDRs) in protein sequences. The literature suggests that the involvement of proteins in phase separation can be predicted from their sequences, leading to the development of over 30 computational predictors. We focused on intrinsic disorder due to its fundamental role in related diseases, and because recent analysis has shown that phase separation can be accurately predicted for structured proteins. We evaluated eight representative amino acid-level predictors of phase separation, capable of identifying phase-separating IDRs, using a well-annotated, low-similarity test dataset under two complementary evaluation scenarios. Several methods generate accurate predictions in the easier scenario that includes both structured and disordered sequences. However, we demonstrate that modern disorder predictors perform equally well in this scenario by effectively differentiating phase-separating IDRs from structured regions. In the second, more challenging scenario—considering only predictions in disordered regions—disorder predictors underperform, and most phase separation predictors produce only modestly accurate results. Moreover, some predictors are broadly biased to classify disordered residues as phase-separating, which results in low predictive performance in this scenario. Finally, we recommend PSPHunter as the most accurate tool for identifying phase-separating IDRs in both scenarios. Full article

The search for selective anticholinergic agents stems from varying cholinesterase levels as Alzheimer’s Disease progresses from the mid-to-late stage and from butyrylcholinesterase’s (BChE) role in β-amyloid plaque formation. While structure-based and pharmacophore-based virtual screening could search from large libraries in a short time, these methods do not consider dynamic features that result from a ligand’s inhibition of the enzyme and consequently may under- or overexaggerate enzyme selectivity of a given ligand. In this computational study, we probed the selectivity of representative secondary metabolite compounds against acetylcholinesterase and BChE through molecular dynamics simulations. The results were evaluated by analysis of the root mean squared deviation of ligand heavy atoms, the radius of gyration of each inhibited and uninhibited enzyme, root mean squared fluctuation of residues, intermolecular interaction energy, and linear interaction energy approximation of the Gibbs free energy of binding. These considerations further reveal the induced-fit characteristics contributing to ChE selectivity that are predominantly due to the greater flexibility of BChE’s active site gorge. Full article

A 12-membered pyridinophane scaffold containing two pyridine and two tertiary amine residues is examined as a prototype ligand (^tBuN4) for supporting nitrene transfer to olefins. The known [(^tBuN4)M^II(MeCN)₂]²⁺ (M = Mn, Fe, Co, and Ni) and [(^tBuN4)Cu^I(MeCN)]⁺ cations are synthesized with the hexafluorophosphate counteranion. The aziridination of para-substituted styrenes with PhI=NTs (Ts = tosyl) in various solvents proved to be high yielding for the Cu(I) and Cu(II) reagents, in contrast to the modest efficacy of all other metals. For α-substituted styrenes, aziridination is accompanied by products of aziridine ring opening, especially in chlorinated solvents. Bulkier β-substituted styrenes reduce product yields, largely for the Cu(II) reagent. Aromatic olefins are more reactive than aliphatic congeners by a significant margin. Mechanistic studies (Hammett plots, KIE, and stereochemical scrambling) suggest that both copper reagents operate via sequential formation of two N–C bonds during the aziridination of styrene, but with differential mechanistic parameters, pointing towards two distinct catalytic manifolds. Computational studies indicate that the putative copper nitrenes derived from Cu(I) and Cu(II) are each associated with closely spaced dual spin states, featuring high spin densities on the nitrene N atom. The computed electrophilicity of the Cu(I)-derived nitrene reflects the faster operation of the Cu(I) manifold. Full article

Aftershocks are inevitable phenomena following a mainshock, especially after a major earthquake. However, the cumulative damage caused by aftershocks and its impact on structural performance evaluation has only recently received significant attention. This study explores the effects of mainshock–aftershock (MS–AS) sequences, including multiple consecutive aftershocks, acting on 3D steel moment-resisting frame structures. Following nonlinear time history analysis, several fundamental variables such as residual interstory drift, maximum displacement, plastic hinge formation, and base shear are evaluated to examine cumulative damage. In this context, the findings depicted in terms of aftershocks play a significant role in exacerbating plastic deformations and damage accumulation in steel moment frames. Subsequently, to mitigate cumulative damage on steel moment frames, retrofitting strategies were implemented. Retrofitting strategies effectively reduce cumulative damage and improve seismic resilience under multiple earthquake events. This research highlights the limitations of single-event seismic assessments and the need to incorporate sequential earthquake effects in design and retrofit practices. Furthermore, it provides new insights into mitigating further damage by retrofitting existing structures under multiple earthquakes. Full article

To address the poor thermal shock resistance and high brittleness of traditional ceramic tools, a novel Si₃N₄/Sc₂W₃O₁₂ (SNS) composite ceramic material was developed via in situ synthesis using WO₃ and Sc₂O₃ as precursors and consolidated by spark plasma sintering. Sc₂W₃O₁₂ with negative thermal expansion was introduced to compensate for matrix shrinkage and modulate interfacial stress. The effects of varying Sc₂W₃O₁₂ content on thermal expansion, residual stress, microstructure, and mechanical properties were systematically investigated. Among the compositions, SNS3 (12 wt.% Sc₂W₃O₁₂) exhibited the best overall performance: relative density of 98.8 ± 0.2%, flexural strength of 712.4 ± 30 MPa, fracture toughness of 7.5 ± 0.3 MPa·m^1/2, Vickers hardness of 16.3 ± 0.3 GPa, and an average thermal expansion coefficient of 2.81 × 10⁻⁶·K⁻¹. The formation of a spherical chain-like Sc-W-O phase at the grain boundaries created a “hard core–soft shell” interface that enhanced crack resistance and stress buffering. Cutting tests showed that the SNS3 tool reduced workpiece surface roughness by 32.91% and achieved a cutting distance of 9500 m. These results validate the potential of this novel multiphase ceramic system as a promising candidate for high-performance and thermally stable ceramic cutting tools. Full article

Various pretreatment methods for the valorization of sunflower husks (SHs) for H₂ gas generation through fermentation by Escherichia coli were investigated. We analyzed thermal treatment (TT), acid hydrolysis (AH), and alkaline hydrolysis (AlkH) at different substrate concentrations (50 g L⁻¹, 75 g L⁻¹, 100 g L⁻¹, and 150 g L⁻¹) and dilution levels (undiluted, 2× diluted, and 5× diluted). A concentration of 75 g L⁻¹ SH that was acid-hydrolyzed and dissolved twice in the medium yielded optimal microbial growth, reaching 0.3 ± 0.1 g cell dry weight (CDW) L⁻¹ biomass. The highest substrate level enabling effective fermentation was 100 g L⁻¹, producing 0.37 ± 0.13 (g CDW) × L⁻¹ biomass after complete fermentation, while 150 g L⁻¹ exhibited pronounced inhibitory effects. It is worth mentioning that the sole alkaline treatment was not optimal for growth and H₂ production. Co-fermentation with glycerol significantly enhanced both biomass formation (up to 0.42 ± 0.15 (g CDW) × L⁻¹)) and H₂ production. The highest H₂ yield was observed during batch growth at 50 g L⁻¹ SH hydrolysate with 5× dilution, reaching up to 5.7 mmol H₂ (g sugar)⁻¹ with glycerol supplementation. This study introduces a dual-waste valorization strategy that combines agricultural and biodiesel industry residues to enhance clean energy generation. The novelty lies in optimizing pretreatment and co-substrate fermentation conditions to maximize both biohydrogen yield and microbial biomass using E. coli, a widely studied and scalable host. Full article

The sustainable valorization of electrolytic manganese residue (EMR) and fly ash (FA) presents critical environmental challenges. This study systematically investigates the performance optimization of EMR-FA ceramic composites through the coordinated regulation of raw material ratios, sintering temperatures, and additive effects. While the composite with 85 g FA exhibits the highest mechanical strength, lowest porosity, and minimal water absorption, the formulation consisting of 45 wt% EMR, 40 wt% FA, and 15 wt% kaolin is identified as a balanced composition that achieves an effective compromise between mechanical performance and solid waste utilization efficiency. Sintering temperature studies revealed temperature-dependent property enhancement, with controlled sintering at 1150 °C preventing the over-firing phenomena observed at 1200 °C while promoting phase evolution. XRD-SEM analyses confirmed accelerated anorthite formation and the morphological transformations of FA spherical particles under thermal activation. Additive engineering demonstrated that 8 wt% CaO addition enhanced structural densification through hydrogrossular crystallization, whereas Na₂SiO₃ induced sodium-rich calcium silicate phases that suppressed anorthite development. Contrastingly, ZrO₂ facilitated zircon nucleation, while TiO₂ enabled progressive performance enhancement through amorphous phase modification. This work establishes fundamental phase–structure–property relationships and provides actionable engineering parameters for sustainable ceramic production from industrial solid wastes. Full article

Aminopeptidase A (APA) cleaves a single aspartate residue from the amino terminus of peptides within the renin angiotensin system (RAS). Since several RAS peptides contain an N-terminal aspartate, we developed an assay to evaluate the effect of recombinant APA on the cleavage of Ang I, Ang II, Ang-(1-7), Ang-(1-9), and Ang-(1-12). The latter peptide has been proposed to be a functional Ang II-forming substrate with a hypertensive action attributable to the formed Ang II acting on AT1 receptors. Here we investigated the following: (a) the hydrolytic action of APA on Ang-(1-12), Ang I (1-10), Ang-(1-9), Ang II and Ang-(1-7) and (b) whether Ang-(1-12) pressor activity is altered by recombinant APA (r-APA) or genetic APA deficiency. We found that (a) r-APA cleaves the N-terminal aspartate of not only Ang II but also [Ang-(1-12), Ang I (1-10), Ang-(1-9)] and [Ang-(1-7)]; (b) the pressor activity of Ang-(1-12) was abolished in the presence of Lisinopril or Telmisartan; (c) r-APA significantly attenuated the pressor activities of infused Ang I and Ang II but not Ang-(1-12); and (d) r-ACE2 also did not attenuate the pressor effect of infused Ang-(1-12). Thus, in addition to increasing blood pressure indirectly via the formation of Ang II, Ang-(1-12) increases blood pressure by an Ang II-independent mechanism. We conclude that APA has an antihypertensive effect attributable to rapid degradation of Ang II, and this action may have a therapeutic potential in forms of hypertension that are Ang II-dependent. In addition, APA metabolizes Ang-(1-12), a peptide that has a prohypertensive action, in part, as a source of Ang II formation but also by a yet to be determined action independent of Ang II. Full article

Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, temperature control, and integration into continuous manufacturing. This study investigates vertical HME as an innovative approach in order to optimize drug polymer interactions and generate stable amorphous dispersions with controlled release behavior. Methods: Extrusion trials were conducted using a vertical hot-melt extruder developed by Rondol Industrie (Nancy, France). Acetylsalicylic acid (ASA) supplied by Seqens (Écully, France) was used as a model API and processed with Soluplus^® and Kollidon^® 12 PF (BASF, Ludwigshafen, Germany). Various process parameters (temperature, screw speed, screw profile) were explored. The extrudates were characterized by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to evaluate crystallinity and microstructure. In vitro dissolution tests were performed under sink conditions using USP Apparatus II to assess drug release profiles. Results: Vertical HME enabled the formation of homogeneous amorphous solid dispersions. PXRD confirmed the absence of residual crystallinity, and SAXS revealed nanostructural changes in the polymer matrix influenced by drug loading and thermal input. In vitro dissolution demonstrated enhanced drug release rates compared to crystalline ASA, with good reproducibility. Conclusions: Vertical HME provides a compact, cleanable, and modular platform that supports the development of stable amorphous dispersions with controlled release. It represents a robust and versatile solution for pharmaceutical innovation, with strong potential for cost-efficient continuous manufacturing and industrial-scale adoption. Full article

The formation of acidic goaf water in abandoned coal mines poses significant environmental threats, especially in karst regions where the risk of groundwater contamination is heightened. This study investigates the geochemical processes responsible for the generation of acidic water through batch and column leaching experiments using coal mine surrounding rocks (CMSR) from Yangquan, China. The coal-bearing strata, primarily composed of sandstone, mudstone, shale, and limestone, contain high concentrations of pyrite (up to 12.26 wt%), which oxidizes to produce sulfuric acid, leading to a drastic reduction in pH (approximately 2.5) and the mobilization of toxic elements. The CMSR samples exhibit elevated levels of arsenic (11.0 mg/kg to 18.1 mg/kg), lead (69.5 mg/kg to 113.5 mg/kg), and cadmium (0.6 mg/kg to 2.6 mg/kg), all of which exceed natural crustal averages and present significant contamination risks. The fluorine content varies widely (106.1 mg/kg to 1885 mg/kg), with the highest concentrations found in sandstone. Sequential extraction analyses indicate that over 80% of fluorine is bound in residual phases, which limits its immediate release but poses long-term leaching hazards. The leaching experiments reveal a three-stage release mechanism: first, the initial oxidation of sulfides rapidly lowers the pH (to between 2.35 and 2.80), dissolving heavy metals and fluorides; second, slower weathering of aluminosilicates and adsorption by iron and aluminum hydroxides reduce the concentrations of dissolved elements; and third, concentrations stabilize as adsorption and slow silicate weathering regulate the long-term release of contaminants. The resulting acidic goaf water contains extremely high levels of metals (with aluminum at 191.4 mg/L and iron at 412.0 mg/L), which severely threaten groundwater, particularly in karst areas where rapid cross-layer contamination can occur. These findings provide crucial insights into the processes that drive the acidity of goaf water and the release of contaminants, which can aid in the development of effective mitigation strategies for abandoned mines. Targeted management is essential to safeguard water resources and ecological health in regions affected by mining activities. Full article

Redox signaling is central to plant adaptation, influencing metabolic regulation, stress responses, and developmental processes through thiol-based oxidative post-translational modifications (oxiPTMs) of redox-sensitive proteins. These modifications, particularly those involving cysteine (Cys) residues, act as molecular switches that alter protein function, structure, and interactions. Advances in mass spectrometry-based redox proteomics have greatly enhanced the identification and quantification of oxiPTMs, enabling a more refined understanding of redox dynamics in plant cells. In parallel, the emergence of computational modeling, artificial intelligence (AI), and machine learning (ML) has revolutionized the ability to predict redox-sensitive residues and characterize redox-dependent signaling networks. This review provides a comprehensive synthesis of methodological advancements in redox proteomics, including enrichment strategies, quantification techniques, and real-time redox sensing technologies. It also explores the integration of computational tools for predicting S-nitrosation, sulfenylation, S-glutathionylation, persulfidation, and disulfide bond formation, highlighting key models such as CysQuant, BiGRUD-SA, DLF-Sul, and Plant PTM Viewer. Furthermore, the functional significance of redox modifications is examined in plant development, seed germination, fruit ripening, and pathogen responses. By bridging experimental proteomics with AI-driven prediction platforms, this review underscores the future potential of integrated redox systems biology and emphasizes the importance of validating computational predictions, through experimental proteomics, for enhancing crop resilience, metabolic efficiency, and precision agriculture under climate variability. Full article

In order to elucidate the high-temperature reaction process of solid waste-based high belite sulphoaluminate cement containing residual gypsum in clinker (NHBSAC) and obtain the formation laws of each mineral in clinker, this article studied its high-temperature reaction kinetics. Through QXRD analysis and numerical fitting methods, the formation of C₄A₃$\overline{\mathrm{S}}$, β-C₂S, and CaSO₄ in clinker under different calcination systems was quantitatively characterized, the corresponding high-temperature reaction kinetics models were established, and the reaction activation energies of each mineral were obtained. The results indicate that the content of C₄A₃$\overline{\mathrm{S}}$ and β-C₂S increases with the prolongation of holding time and the increase in calcination temperature, while CaSO₄ is continuously consumed. Under the control mechanism of solid-state reaction, the formation and consumption of minerals follow the kinetic equation. C₄A₃$\overline{\mathrm{S}}$ and β-C₂S satisfy the D₄ equation under diffusion mechanism control, and CaSO₄ satisfies the R₃ equation under interface chemical reaction mechanism control. The activation energy required for mineral formation varies with different temperature ranges. The activation energies required to form C₄A₃$\overline{\mathrm{S}}$ at 1200–1225 °C, 1225–1275 °C, and 1275–1300 °C are 166.28 kJ/mol, 83.14 kJ/mol, and 36.58 kJ/mol, respectively. The activation energies required to form β-C₂S at 1200–1225 °C and 1225–1300 °C are 374.13 kJ/mol and 66.51 kJ/mol, respectively. This study is beneficial for achieving flexible control of the mineral composition of NHBSAC clinker, providing a theoretical basis and practical experience for the preparation of low-carbon cement and the optimization design of its mineral composition. Full article

Phosphorous slag is an industrial by-product generated in the process of producing yellow phosphorus by electric furnace, which occupies a substantial number of land resources and causes serious environmental pollution. The comprehensive utilization of phosphorous slag is a major topic relevant to the sustainability of the yellow phosphorus industry. In this paper, we attempted to utilize phosphorous slag as a supplementary cementing material to prepare silica-aluminum based cementitious material (SAC-PHS). To determine how phosphorus influences the early-age hydration reaction process of silica-aluminum based cementitious material, three groups of samples, PHS₂₀, PHS₂₅, and PHS₃₀, with better mechanical properties were selected to deeply investigate their one-week hydration characteristics. Characterization results showed that the main hydration products of SAC-PHS were C-A-S-H gels and ettringite. PHS₂₅ specimen produced more C-A-S-H gels and ettringite than the other two samples after one-week hydration. Interestingly, the P/Si atomic ratio indicated that chemical bonds were formed between Si and P during the formation of C-A-S-H gels, which improved the strength of SAC-PHS. Our findings offer valuable insights for the application of phosphorous slag in construction and building materials and promote the efficient resource utilization of phosphorous residue. Full article