Search Results (2,790)

Redox flow batteries (RFBs) are a promising technology for large-scale energy storage due to their safety, scalability, and design flexibility. This study investigated a tiron-A (4,5-dihydroxybenzene-1,3-disulfonic acid)/tungstosilicic acid (TSA) RFB system, focusing on optimizing the supporting electrolyte and the volumetric ratio of the catholyte (tiron-A) to anolyte (TSA). Electrochemical characteristics, confirmed by CV and EIS, showed that sulfuric acid was the most suitable supporting electrolyte due to its excellent cell potential and lower ohmic resistance compared to sodium chloride and sodium hydroxide electrolytes. To address the inherent electron capacity imbalance between tiron-A (two electrons) and TSA (four electrons), various volumetric ratios were evaluated. The cell with the 3:1 tiron-A:TSA ratio exhibited optimal performance, achieving the highest discharge capacity, excellent cycle stability, and consistent energy efficiency. The electrochemical impedance spectroscopy results revealed that the ohmic resistance was minimized at the 3:1 ratio. This stable, low-ohmic resistance, coupled with a significant reduction in charge transfer resistance after cycling, was confirmed as the dominant factor for the improved long-term performance. These findings demonstrate an effective strategy for developing a high-performance performance tiron-A/TSA RFB system. Full article

Ternary hybrid nanofluid have been revealed to possess a wide range of application disciplines reaching from biomedical engineering, detection of cancer, over or photovoltaic panels and cells, nuclear power plant engineering, to the automobile industry, smart cells and and eventually to heat exchange systems. Inspired by the recent developments in nanotechnology and in particular the high potential ability of use of such nanofluids in practical problems, this paper deals with the flow of a three phase nanofluid of MWCNT-Au/Ag nanoparticles dispersed in blood in the presence of a bidirectional stretching sheet. The model derived in this study yields a set of linked nonlinear PDEs, which are first transformed into dimensionless ODEs. From these ODEs we get a dataset with the help of MATHEMATICA environment, then solved using AI-based technique utilizing Levenberg Marquardt Feedforward Algorithm. In this work, flow characteristics under varying physical parameters have been studied and analyzed and the boundary layer phenomena has been investigated. In detail horizontal, vertical velocity profiles as well as temperature distribution are analyzed. The findings reveal that as the stretching ratio of the surface coincide with an increase the vertical velocity as the surface has thinned in this direction minimizing resistance to the fluid flow. Full article

Introduction: Primary glomerulopathies are immune-driven kidney diseases. IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN) are prevalent entities with a risk of chronic progression. Immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, regulate activation and tolerance in T, B, and NK cells, and also exist in soluble forms, reflecting systemic immune balance. Objective: To compare immune checkpoint profiles in IgAN and MPGN versus healthy volunteers (HV) through surface expression, soluble serum levels, and PBMC transcripts, with attention to sex-related differences and diagnostic value assessed by ROC curves. Materials and Methods: Ninety age-matched subjects were studied: IgAN (n = 30), MPGN (n = 30), HV (n = 30). Flow cytometry evaluated checkpoint expression on CD4+/CD8+ T cells, CD19+ B cells, and NK cells. ELISA quantified sPD-1, sPD-L1, sCTLA-4, sCD86, sCD200, sCD200R; PBMC transcript levels were assessed. Group comparisons, sex stratification, and ROC analyses were performed. Results: Lymphocyte distributions were preserved, but IgAN patients showed anemia and impaired renal function, while MPGN patients had greater proteinuria and dyslipidemia. GN patients displayed increased PD-1/PD-L1 and CD200R/CD200, with reduced CTLA-4/CD86, compared to HV. Serum analysis revealed elevated sPD-1, sPD-L1, sCD200, sCD200R and decreased sCTLA-4, sCD86. PBMC transcripts paralleled these trends, with PD-1/PD-L1 mainly increased in MPGN. Sex had minimal impact. ROC analyses showed strong GN vs. HV discrimination by CD19⁺CTLA-4⁺, PD-1/PD-L1, and CD200/CD200R, but limited ability to separate IgAN from MPGN. Conclusions: IgAN and MPGN share a sex-independent checkpoint signature: PD-1/PD-L1 and CD200R/CD200 upregulation with CTLA-4/CD86 downregulation. CD19⁺, CTLA-4⁺, and soluble PD-1/PD-L1/CD200(R) emerge as promising biomarkers requiring further validation. Full article

In the production of recombinant antibody/Fc-fusion proteins using mammalian cells, many aggregates often form alongside the target proteins, particularly with bispecific antibodies. To ensure the safety of biological products, it is essential to control the amount of aggregates within a specific range. A traditional downstream process typically involves using Protein A (ProA) resin to capture the target antibody, followed by two polishing steps to ensure purity; for instance, using an anion exchange chromatography (AEX) in flow-through mode and a cation exchange chromatography (CEX) in binding–elution mode. In this study, we choose a Dual Action Fab (DAF), which can bind two antigens and is prone to aggregation when expression in CHO (Chinese Hamster Ovary) cells. We introduce hydrophobic interaction membrane chromatography (HIMC) operating in flow-through mode, which enhances production efficiency while reducing costs and the risks associated with column packing. We evaluated the impact of the operating buffer system, as well as the pH and conductivity of the loading samples, on aggregate removal using HIMC. Additionally, we investigated the mechanism of aggregate binding and found that loading conditions had a limited impact on this process. Overall, our findings indicate that employing HIMC can achieve a 20% reduction in aggregate levels. These results demonstrate that HIMC in flow-through mode is an effective and robust approach for reducing aggregates during antibody purification. Full article

The development of FGFR1-driven stem cell leukemia and lymphoma syndrome (SCLL) in mouse models is accompanied by an increase in highly heterogenous myeloid derived suppressor cells (MDSCs), which promote immune evasion. To dissect this heterogeneity, we used a combination of CyTOF and scRNA-Seq to define the phenotypes and genotypes of these MDSCs. CyTOF demonstrated increased levels of circulating macrophages in the peripheral blood of leukemic mice, and flow cytometry demonstrated that these macrophages were derived from Ly6C^Hi M-MDSC as well as the Ly6C^Int and Ly6C^Low monocytic populations. Consistently, scRNA-Seq analysis demonstrated the accumulation of non-classical monocytes (ncMono) during leukemia progression, which also express macrophage markers. These leukemia-induced macrophages show continuous transcriptional reprogramming during leukemia progression, with the upregulation of cellular stress response genes Hspa1a and Hspa1b and inflammation-related gene Nfkbia. Trajectory analysis revealed a transition from classical monocytes (cMono) to ncMono, and potential genes orchestrating this transition process have been identified. Furthermore, T-cell suppression assays demonstrated the immune suppressive abilities of leukemia-induced circulatory macrophages. Targeting these macrophages with the GW2580 CSF1R inhibitor leads to restored immune surveillance and improved survival. Overall, we demonstrate that circulating macrophages are responsible, at least in part, for the immune suppression in SCLL leukemia models, and targeting macrophages in this system improves the survival of leukemic mice. Full article

Allogeneic chondrocyte therapies present an attractive alternative to existing autologous therapies for the repair of cartilage defects, enabling the selection of optimal donor cells and streamlined manufacturing processes. This study investigates the potential of juvenile chondrocytes derived from human infantile (aged 0–4 y) polydactyly digits and the iliac apophysis for cartilage repair using Good Manufacturing Practice bioreactor expansion. Iliac apophysis (n = 4) and polydactyly tissues (n = 4) were assessed histologically. Chondrocytes were isolated enzymatically and cultured using standard tissue culture plastic (TCP) methodology. Upon sufficient cell expansion, chondrocytes were seeded into the Quantum^® bioreactor system or onto TCP (±vitronectin coating). The manufactured chondrocytes growth rates, total cell yields, chondrogenic pellet forming capacity (GAG/DNA, histology), immunoprofiles (flow cytometry) and gene expression (RT-qPCR) were assessed. Equivalent chondrocyte numbers were isolated from polydactyly and iliac apophysis donors per wet weight of tissue. Quantum^®-expanded chondrocytes from both sources yielded comparable cell numbers; however, growth was slowed in the Quantum^® compared to TCP. Polydactyly and iliac apophysis-derived chondrocytes expressed chondrocyte cell surface markers (CD166, CD44, CD151, SOX9) and formed chondrogenic pellets. Quantum^® bioreactor expansion did not alter, gene expression or capacity to form glycosaminoglycans (GAGs (normalised to DNA content)) compared to matched TCP expansion. Juvenile cartilage donors are a promising chondrocyte source for the development of an allogeneic therapy. This novel study expanding juvenile chondrocytes in the Quantum^® GMP-compliant bioreactor suggests that culture conditions may need modification to improve growth, whilst retaining cartilage forming capacity. Full article

The development of low-resistance blood flow within the developing placenta in the early weeks of pregnancy requires trophoblast invasion of the uterine spiral arteries. Therefore, understanding the migration and differentiation of trophoblasts is necessary. Recently, researchers have focused increasingly on the regulation of the response of endovascular extravillous trophoblasts (enEVTs) to mechanical stimuli associated with shear stress. The starting point for these studies is that enEVTs, which adopt a pseudoendothelial phenotype, functionally resemble endothelial cells in terms of ability to promote angiogenesis, vascular remodeling and cell–cell communication. The complex process of mechanotransduction requires the coordinated participation of many types of mechanoreceptors, whose activated signaling pathways are translated into whole-cell mechanosensing involving components of the cytoskeleton and extracellular matrix. The aim of this review is to comprehensively present the current knowledge on the importance of mechanical stimuli associated with shear stress in the development of local changes in the vascular system at the site of blastocyst implantation. The characteristics of individual mechanoreceptors are determined, and the most important factors influencing mechanotransduction are discussed. Understanding the importance of mechanosensing disorders in trophoblasts in the pathogenesis of unexplained recurrent abortions or preeclampsia may be helpful in the development of new therapeutic strategies based on the regulation of mechanotransduction in response to shear stress. Full article

Cells of the innate immune system, particularly natural killer (NK) cells, serve as the first line of defense against tumor development and play a critical role in antitumor immunity. Characterizing the immune cell pool and its functional state is essential for understanding immunotherapy mechanisms and identifying key cellular players. However, defining NK cell populations in mice, the primary model for cancer immunotherapy, is challenging due to strain-specific marker variability and the absence of a universal NK cell marker, such as human CD56. This study evaluates surface markers of NK and other peripheral blood immune cells in both humans and mice, associating these markers with specific functional profiles. Bioinformatic approaches are employed to visualize these markers, enabling rapid immunoprofiling. We explore the translational relevance of these markers in assessing immunotherapy efficacy, including their gene associations, ligand interactions, and interspecies variations. Markers compatible with rapid flow-cytometry-based detection are prioritized to streamline experimental workflows. We propose a standardized immunoprofiling strategy for monitoring systemic immune status and evaluating the effectiveness of immunotherapy in preclinical and clinical settings. This approach facilitates the design of preclinical studies that aim to identify predictive biomarkers for immunotherapy outcomes by monitoring immune status. Full article

As the demand for biodiesel continues to rise, there is a pressing need for efficient and continuous monitoring of the transesterification reaction at the industrial level. However, there is a lack of straightforward online monitoring methods capable of accurately following the course of ethanolysis under various reaction conditions. In this work, simple linear regression (SLR) and multiple linear regression (MLR) models were developed to assess Fourier transform infrared spectroscopy (FTIR) data from a continuous flow cell, enabling real-time ethanolysis monitoring without sample pretreatment. Gas chromatography (GC) was utilised as the reference method to accurately characterise the reaction mixture’s composition during ethanolysis. Extensive correlation analysis was performed to identify spectra regions where the reaction system’s state changes are observable. The gained regions were subsequently applied in the linear regression model’s development. This novel approach resulted in the performance of simple linear regression comparable to complex partial least squares (PLS) regression model (RMSEP = 2.11). The developed online monitoring system was validated in a wide range of reaction conditions (40–60 °C; 0.25–1.0% w/w NaOH); it effectively identifies dynamic changes in the ethanolysis process and confirms achieving the threshold value of ester content set by EU regulation directly in the production process. Full article

The microparticle-enhanced microfiltration is a technique that combines the use of microparticulate adsorbent material dispersed in aqueous solution and microfiltration membranes for the removal of ions and emerging contaminants with low energy consumption. Thus, the objective of this work was to synthesize an organoclay, BAPTES, based on bentonite and (3-aminopropyl)triethoxysilane for use as a semi-synthetic adsorbent material in the microparticle-enhanced microfiltration process for the removal of AR27 in aqueous systems. For this purpose, the obtained organoclay was structurally characterized by FTIR-ATR-FEDS, SEM-EDS, DLS, and thermal analysis. In addition, equilibrium adsorption and kinetic studies of AR27 were performed. The results showed a significant increase in the adsorption capacity of AR27 by organoclay (86.06%) compared to natural bentonite (2.10%), due to the presence of ionizable amino groups in the organoclay structure that promote electrostatic interactions with the dye. Furthermore, kinetic studies showed that the adsorption process follows a pseudo-first-order model and that the equilibrium data better fits the Temkin model, indicating a heterogeneous adsorption surface with different binding energies. The evaluation of enhanced microfiltration with BAPTES microparticles showed that the adsorption capacity obtained in continuous flow experiments (14.25–33.63 mg g⁻¹) was lower than that determined experimentally under equilibrium conditions (~39.5 mg g⁻¹), suggesting that the residence time of the analyte and the adsorbent in the filtration cell is a determining factor in the retention values obtained. In addition, desorption studies revealed that basic pH had a greater effect than the presence of salts and the use of ethanol, favoring the weakening of the AR27-BAPTES interaction. Finally, the results highlight the potential use of BAPTES microparticle-enhanced microfiltration in applications involving the treatment of contaminated industrial effluents. Full article

The study of aquatic biodiversity in the context of ecosystem sustainability is of urgent research importance, with several existing knowledge gaps. Among the under-studied groups are silica-scaled chrysophytes. Their cells are covered with silica scales and bristles/spines, the species-specific structure of which can be distinguished only by electron microscopy. In June and August 2024, samples were collected from a broad aquatic system comprising the southern part of Lake Baikal and a cascade of four reservoirs formed after the construction of hydroelectric dams on the Angara River flowing from Lake Baikal. Using electron microscopy, we identified 45 species of silica-scaled chrysophytes in phytoplankton in 2024, and the overall checklist was expanded to 57, accounting for interannual differences. Clear differences in species composition and richness were observed both between seasons and among reservoirs. Approximately a quarter of the recorded species were heterotrophs, which do not contribute to primary production, whereas 44% were phototrophs and 31% mixotrophs, both groups contributing to the Si cycle and to primary production. Continuous monitoring of reservoirs is essential for understanding the processes shaping silica-scaled chrysophytes diversity and may serve as an additional criterion for assessing the sustainability and transformation of freshwater ecosystems. Full article

Filtration of submicron particles and nanoparticles is an important problem in nano-industry and in air conditioning and ventilation systems. The presence of submicron particles comprising fungal spores, bacteria, viruses, microplastic, and tobacco-smoke tar in ambient air is a severe problem in air conditioning systems. Many nanotechnology material processes used for catalyst, solar cells, gas sensors, energy storage devices, anti-corrosion and hydrophobic surface coating, optical glasses, ceramics, nanocomposite membranes, textiles, and cosmetics production also generate various types of nanoparticles, which can retain in a conveying gas released into the atmosphere. Particles in this size range are particularly difficult to remove from the air by conventional methods, e.g., electrostatic precipitators, conventional filters, or cyclones. For these reasons, nanofibrous filters produced by electrospinning were developed to remove fine particles from the post-processing gases. The physical basis of electrospinning used for nanofilters production is an employment of electrical forces to create a tangential stress on the surface of a viscous liquid jet, usually a polymer solution, flowing out from a capillary nozzle. The paper presents results for investigation of the filtration process of metal oxide nanoparticles: TiO₂, MgO, and Al₂O₃ by electrospun nanofibrous filter. The filter was produced from polyvinylidene fluoride (PVDF). The concentration of polymer dissolved in dimethylacetamide (DMAC) and acetone mixture was 15 wt.%. The flow rate of polymer solution was 1 mL/h. The nanoparticle aerosol was produced by the atomization of a suspension of these nanoparticles in a solvent (methanol) using an aerosol generator. The experimental results presented in this paper show that nanofilters made of PVDF with surface density of 13 g/m² have a high filtration efficiency for nano- and microparticles, larger than 90%. The gas flow rate through the channel was set to 960 and 670 l/min. The novelty of this paper was the investigation of air filtration from various types of nanoparticles produced by different nanotechnology processes by nanofibrous filters and studies of the morphology of nanoparticle deposited onto the nanofibers. Full article

A 47-year-old woman presented with a two-year history of progressive visual symptoms and headaches. Lumbar puncture revealed lymphocytic pleocytosis, elevated protein, low glucose, and a CSF CrAg titer of 1:256. She was treated empirically for cryptococcal meningitis with amphotericin B, flucytosine, and fluconazole for 15 months. Her symptoms persisted, and repeated CSF and serum CrAg, fungal cultures, and an extensive infectious workup were negative. CSF flow cytometry eventually demonstrated a monoclonal B-cell population suggestive of a lymphoproliferative process. Imaging, including MRI and PET scans, did not reveal systemic disease. A ventriculoperitoneal (VP) shunt was placed for symptom management. This case emphasizes the limitations of CrAg testing and the potential for false positives. It underscores the need for integrating clinical, laboratory, and imaging data when evaluating chronic meningitis. Full article

The expanded newborn screening (NBS) program in the Russian Federation, launched in 2023, includes the detection of severe forms of T- and B-cell immunodeficiencies via TREC/KREC quantification. We report a rare case of a male infant having multiple congenital anomalies and lymphopenia identified through this program. Genetic testing revealed a 25.8 Mb terminal deletion spanning 13q31.2–qter, consistent with 13q deletion syndrome. Initial NBS revealed reduced TREC levels, prompting further evaluation. The patient exhibited a complex phenotype, including central nervous system malformation (alobar holoprosencephaly), severe congenital heart disease, renal hypoplasia, limb and genitourinary anomalies, and facial dysmorphism. Postnatal complications included pneumonia, pleuritis, and chylothorax. Flow cytometry demonstrated mild T- and B-cell lymphopenia. The genomic defect was characterized using long-read third-generation sequencing, enabling precise breakpoint identification and accurate mapping of deleted genes. The deletion was confirmed via subtelomeric FISH analysis. The patient died at 7 months of age due to the progression of underlying congenital anomalies and associated complications. Our findings broaden the clinical characterization of distal 13q deletion syndrome and demonstrate the value of long-read sequencing in structural chromosomal analysis. They further highlight the difficulties of caring for neonates having complex malformations and immune dysfunction. Given the potential for both primary and secondary immune disturbances, comprehensive immunological evaluation should be considered in patients having 13q deletion syndrome to improve diagnostic accuracy and inform appropriate clinical management. Full article

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by sustained neuroinflammation and demyelination within the central nervous system (CNS). Vesatolimod (VES), a selective Toll-like receptor 7 (TLR7) agonist, has demonstrated both antiviral and immunomodulatory properties; however, its potential therapeutic value in neuroinflammatory contexts remains poorly understood. In this study, we evaluated the efficacy of VES in the experimental autoimmune encephalomyelitis (EAE) model of MS and elucidated its mechanisms of action. EAE was induced in mice by immunization with myelin oligodendrocyte glycoprotein (MOG_35–55). The therapeutic effects of VES were assessed through clinical scoring, body weight monitoring, histopathology, flow cytometry, quantitative proteomics, and Western blot analysis. Additionally, an in vitro model of lipopolysaccharide (LPS)-induced microglial activation was employed to investigate cell-autonomous mechanisms. Results showed that VES administration significantly ameliorated disease severity, reduced weight loss, and enhanced neurological function in EAE mice. Treatment with VES inhibited the differentiation of pro-inflammatory Th1 and Th17 cells while expanding regulatory T cell (Treg) populations. It also preserved blood–brain barrier (BBB) integrity, attenuated demyelination, and modulated microglial activation phenotypes within the CNS. At the molecular level, VES activated the Nrf2/HO-1 antioxidant pathway, thereby enhancing the expression of cytoprotective proteins. Proteomic profiling further revealed the downregulation of inflammation-related proteins, specifically those associated with TNF, IL-17, and NOD-like receptor signaling pathways. Collectively, these findings demonstrate that VES alleviates neuroinflammation in EAE through multimodal mechanisms—including peripheral and central immune regulation, BBB protection, and activation of endogenous antioxidant defenses—supporting its further development as a promising therapeutic candidate for MS. Full article