Search Results (844)

Anion exchange membrane (AEM) water electrolysis is a potentially inexpensive and efficient source of hydrogen production as it uses effective low-cost catalysts. The catalytic activity and performance of nickel iron oxide (NiFeO_x) catalysts for hydrogen production in AEM water electrolyzers were investigated. The NiFeO_x catalysts were synthesized with various iron content weight percentages, and at the stoichiometric ratio for nickel ferrite (NiFe₂O₄). The catalytic activity of NiFeO_x catalyst was evaluated by linear sweep voltammetry (LSV) and chronoamperometry for the oxygen evolution reaction (OER). NiFe₂O₄ showed the highest activity for the OER in a three-electrode system, with 320 mA cm⁻² at 2 V in 1 M KOH solution. NiFe₂O₄ displayed strong stability over a 600 h period at 50 mA cm⁻² in a three-electrode setup, with a degradation rate of 15 μV/h. In single-cell electrolysis using a X-37 T membrane, at 2.2 V in 1 M KOH, the NiFe₂O₄ catalyst had the highest activity of 1100 mA cm⁻² at 45 °C, which increased with the temperature to 1503 mA cm⁻² at 55 °C. The performance of various membranes was examined, and the highest performance of the tested membranes was determined to be that of the Fumatech FAA-3-50 and FAS-50 membranes, implying that membrane performance is strongly correlated with membrane conductivity. The obtained Nyquist plots and equivalent circuit analysis were used to determine cell resistances. It was found that ohmic resistance decreases with an increase in temperature from 45 °C to 55 °C, implying the positive effect of temperature on AEM electrolysis. The FAA-3-50 and FAS-50 membranes were determined to have lower activation and ohmic resistances, indicative of higher conductivity and faster membrane charge transfer. NiFe₂O₄ in an AEM water electrolyzer displayed strong stability, with a voltage degradation rate of 0.833 mV/h over the 12 h durability test. Full article

T cells play a vital role in resisting pathogen invasion and maintaining immune homeostasis. However, T cells gradually become exhausted under chronic antigenic stimulation, and this exhaustion is closely related to mitochondrial dysfunction in T cells. Mitochondria play a crucial role in the metabolic reprogramming of T cells to achieve the desired immune response. Here, we compiled the latest research on how mitochondrial metabolism determines T cell function and differentiation, with the mechanisms mainly including mitochondrial biogenesis, fission, fusion, mitophagy, and mitochondrial transfer. In addition, the alterations in mitochondrial metabolism in T-cell exhaustion were also reviewed. Furthermore, we discussed intervention strategies targeting mitochondrial metabolism to reverse T cell exhaustion in detail, including inducing PGC-1α expression, alleviating reactive oxygen species (ROS) production or hypoxia, enhancing ATP production, and utilizing mitochondrial transfer. Targeting mitochondrial metabolism in exhausted T cells may achieve the goal of reversing and preventing T cell exhaustion. Full article

The generation of memory CD8⁺ T cells is essential for establishing protective T cell immunity against pathogens and cancers. However, the cellular and molecular mechanisms underlying memory CD8⁺ T cell formation remain incompletely understood. Reliance on specific pathogen-free (SPF) models, characterized by restricted microbial exposure, may limit our understanding of physiologically relevant immune memory development. This study reveals that CD1d-restricted NKT cells regulate central memory T cell (TCM) generation exclusively in a microbe-rich (“dirty”) environment. Under non-SPF housing, CD1d⁺/⁻ and Ja18⁺/⁻ mice exhibited enhanced TCM formation compared to NKT-deficient controls (CD1d⁻/⁻/Ja18⁻/⁻), demonstrating that microbial experience is required for NKT-mediated TCM regulation. Mechanistically, CD1d-restricted NKT cells increased IL-15Rα expression on CD4⁺ T cells in CD1d⁺/⁻ mice, potentiating IL-15 trans-presentation and thereby activating the IL-15/pSTAT5/Eomes axis critical for TCM maintenance. Functional validation through adoptive transfer of CFSE-labeled OT-1 memory cells revealed an NKT cell-dependent survival advantage in CD1d⁺/⁻ hosts. This provides direct evidence that microbiota-experienced niches shape immune memory. Collectively, these findings establish CD1d-restricted NKT cells as physiological regulators of TCM generation and suggest their potential utility as vaccine adjuvants to enhance protective immunity. Full article

Heart failure (HF) has become an epidemic, with a prevalence of ~7 million cases in the USA. Despite accounting for nearly 50% of all HF cases, heart failure with a preserved ejection fraction (HFpEF) remains challenging to treat. Common pathophysiological mechanisms in HFpEF include oxidative stress, microvascular dysfunction, and chronic unresolved inflammation. Our lab focuses on oxidative stress-mediated cellular dysfunction, particularly the toxic effects of lipid peroxidation products like 4-hydroxy-2-nonenal (4HNE). Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, plays a vital role in detoxifying 4HNE and thereby protecting the heart against pathological stress. ALDH2 activity is reduced in various metabolic stress-mediated cardiac pathologies. The dysfunction of coronary vascular endothelial cells (CVECs) is critical in initiating HFpEF development. Thus, we hypothesized that ectopic overexpression of ALDH2 in CVECs could mitigate metabolic stress-induced HFpEF pathogenesis. In this study, we tested the efficacy of intracardiac injections of the ALDH2 gene into CVECs in db/db mice—a model of obesity-induced type 2 diabetes mellitus (T2DM)—and their controls, db/m mice, by injection with ALDH2 constructs (AAV9-VE-cadherin-hALDH2-HA tag-P2A) or control constructs (AAV9-VE-cadherin-HA tag-P2A-eGFP). We found that intracardiac ALDH2 gene transfer increased ALDH2 levels specifically in CVECs compared to other myocardial cells. Additionally, we observed increased ALDH2 levels and activity, along with decreased 4HNE adducts, in the hearts of mice receiving ALDH2 gene transfer compared to control GFP transfer. Furthermore, ALDH2 gene transfer to CVECs improved diastolic function compared to GFP control alone. In conclusion, ectopic ALDH2 expression in CVECs can contribute, at least partially, to the amelioration of HFpEF. Full article

Background/Objectives: 5-Aminolevulinic acid (5-ALA) is a biosynthetic precursor of heme that induces heme oxygenase-1 (HO-1). Therapeutic induction of HO-1 has shown effectiveness in various autoimmune disease models, including type 1 diabetes (T1D). However, the efficacy of 5-ALA as an HO-1 inducer in T1D models remains unexplored. This study aimed to investigate the therapeutic efficacy of oral 5-ALA administration in preventing autoimmune diabetes development in nonobese diabetic (NOD) mice. Methods: We evaluated diabetes incidence, levels of insulin autoantibody, and severity of insulitis in 5-ALA-treated and control NOD mice. HO-1 expression of dendritic cells in the pancreatic islets and spleen of 5-ALA-treated NOD mice was measured. The IFN-γ/IL-17 of islet-infiltrating T cells and IL-10/IL-12 productions of dendritic cells in the spleen of 5-ALA-treated NOD mice were assessed. We stimulated islet antigen-specific CD4⁺ T cells with islet antigen-pulsed dendritic cells in the presence of 5-ALA and examined the proliferation of the T cells. Finally, we adoptively transferred islet antigen-specific CD4⁺ T cells into 5-ALA-treated, immunodeficient NOD-Rag1 knockout mice, and diabetes incidence in recipients was determined. Results: Oral 5-ALA treatment did not significantly impact diabetes incidence, levels of insulin autoantibody, and insulitis. No significant difference was observed in HO-1 expression in dendritic cells and cytokine production of T cells and dendritic cells. Similarly, there was no significant difference in the proliferation of islet antigen-specific CD4⁺ T cells in vitro and diabetes induction in transfer experiments. Conclusions: Oral administration of 5-ALA has a limited effect on suppressing the development of autoimmune diabetes in NOD mice. Full article

Background/Objectives: Recombinant Fc proteins have been produced that have a protective effect in mouse models of arthritis, such as the K/BxN rheumatoid arthritis model. We have previously shown that a recombinant human IgG1 Fc with a point mutation at position 309, replacing a leucine with a cysteine, fused to the human IgM tailpiece to form a human IgG1 Fc hexamer, rFc-µTP-L309C, effectively prevents neutrophil infiltration into the joints and ameliorates arthritis in the K/BxN serum transfer model and in the endogenous chronic arthritis K/BxN model. We have now investigated the effect of rFc-µTP-L309C on T-cells in the K/BxN chronic arthritis mouse model. Methods: PBMCs were isolated from the spleen, lymph nodes and joint synovial fluid from K/BxN mice having severe chronic arthritis that had been treated with 200 mg/kg rFc-µTP-L309C or human serum albumin (HSA). Flow cytometry was used to isolate the activated CD4⁺CD44⁺ T-cells and T-regulatory cells (Tregs). Intracellular staining was used to identify Th1 and Th17 T-cell subsets, and CD4⁺CD25⁺FoxP3⁺ Tregs. ELISA was used to measure levels of IL-10 and TGF-β in synovial fluid. Results: We find that amelioration of the arthritis occurs after treatment with rFc-µTP-L309C and results in a decrease in Th1 cells’ production of IFNγ and Th17 cells’ production of IL-17. Amelioration also results in decreased production of GM-CSF. Moreover, amelioration results in increased Tregs and IL-10 production in the synovial fluid. Conclusions: rFc-µTP-L309C reduces the inflammatory T-cells and increases the regulatory anti-inflammatory T-cells in the chronic arthritis K/BxN mouse model. This effect explains, in part, the ability of rFc-µTP-L309C to ameliorate the arthritis and reduce damage on the articular cartilage of K/BxN mice. Full article

The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice’s body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome. Full article

This paper investigates and assesses the potential applicability of global mass transfer coefficients derived from large-scale experiments to the bubble growth of a single bubble in a super-saturated flow $(\sigma =9)$. Therefore, it presents, for a specific flow velocity $(u=1{\displaystyle \frac{\mathrm{m}}{\mathrm{s}}}, Re=\mathrm{10,678})$, a comparison between correlation-based modelling and 3D Large Eddy Simulation–Volume of Fluid (LES-VOF) Computational Fluid Dynamics (CFD) simulations (minimum cell size of 10 µm, Δt = 10 µs). After the verification of the CFD with pool nucleation bubbles, two cases are regarded: (1) the bubble flowing in the bulk and (2) a bubble on a wall with a crossflow. The correlation-based modelling results in a nearly linear relationship between bubble radius and time; meanwhile, theoretically, the self-similarity rule offers $r~{Bt}^{0.5}$. The Avdeev correlation gives the best agreement with the CFD simulation for a bubble in the flow bulk (case 1), while the laminar approach for calculation of the exposure time of the penetration theory shows good agreement with the CFD simulation for the bubble growth at the wall (case 2). This preliminary study provides the first quantitative validation of global mass transfer coefficient correlations at the single-bubble scale, suggesting that computationally intensive CFD simulations may be omitted for rapid estimations. Future work will extend the analysis to a wider range of flow velocities and bubble diameters to further validate these findings. Full article

This review summarizes the current knowledge on the probiotic characteristics of dairy propionibacteria, represented by Propionibacterium freudenreichii and some Acidipropionibacterium species commonly consumed through raw milk cheese. For example, in Swiss-type cheeses, P. freudenreichii is added as a starter culture. Some strains of P. freudenreichii have been included in mixed probiotic commercial preparations or used to produce tablets from fermented culture media containing bioactive substances such as short-chain fatty acids (SCFAs), bifidogenic molecules, and vitamins. Acidipropionibacterium acidipropionici and A. jensenii strains have mainly been evaluated as health and productivity promoters in farm animals. For P. freudenreichii, the molecular mechanisms behind its probiotic action have been well elucidated, and recently, novel potential applications have been demonstrated in animal models. P. freudenreichii strains have been shown to mitigate inflammatory bowel diseases (IBDs) and mucositis and prevent necrotizing enterocolitis (NEC) in newborns. Their immunomodulation capacity has alleviated symptoms of food allergies, obesity, diabetes, colorectal cancer (CRC), and infections. Moreover, P. freudenreichii inhibited osteoclastogenesis in a rheumatoid arthritis model. Most observed effects are mediated by proteins on the cell surface or contained in extracellular vesicles (EVs) such as the surface layer (S-layer) protein SlpB, DlaT, and GroEL. No safety issues have been reported for these bacteria. However, investigations into transferable antibiotic resistance traits are still needed, and clinical trials are required to evaluate their effectiveness as probiotics for humans. Full article

Interference competition, wherein bacteria actively antagonize and damage their microbial neighbors, is a key ecological strategy governing microbial community structure and composition. To gain a competitive edge, bacteria can deploy a diverse array of antimicrobial weapons—ranging from diffusible toxins to contact-mediated systems in order to eliminate their bacterial rivals. Among Gram-negative bacteria, the type VI secretion system (T6SS) has emerged as a potent and sophisticated contact-dependent mechanism that enables the delivery of toxic cargo into neighboring cells, thereby promoting the colonization and dominance of a bacterial taxon within an ecological niche. In this review, we examine the ecological significance of T6SS-mediated interference competition by members of the Vibrionaceae family across a range of marine habitats that include free-living microbial communities and host-associated niches such as coral and squid symbioses. Additionally, we explore the ecological impact of T6SS-mediated competition in modulating biofilm community structure and promoting horizontal gene transfer within those complex microbial populations. Together, these insights underscore the ecological versatility of the T6SS and emphasize its role in driving antagonistic bacterial interactions and shaping microbial community dynamics within marine ecosystems. Full article

Cancer/testis antigen (CTA) gene products are expressed in most malignant tumours, while under normal conditions their expression is primarily restricted to testicular cells. In this study, we investigated the prophylactic application of a xenogeneic (ram-derived) testicular cell (TC) vaccine for cancer prevention in an experimental animal model. C57BL/6 mice were immunised three times with either xenogeneic (ram) or syngeneic (mouse) formaldehyde-fixed spermatogenic tissue-derived cells. Following vaccination, mice were implanted with live B16 melanoma or LLC carcinoma cells. Tumour-bearing mice were subsequently assessed for survival and immunological parameters indicative of anti-cancer immunity. Xenogeneic vaccination with TCs induced cross-reactive immune responses to both B16 melanoma and LLC carcinoma antigens (Ags), as determined by an MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Prophylactic vaccination with xenogeneic TCs (xTCs), but not syngeneic TCs (sTCs), significantly improved survival rates, with 30% of vaccinated mice surviving after LLC carcinoma implantation. The induced immunity was long-lasting as mice implanted with LLC carcinoma cells 3–6 months post-vaccination exhibited prolonged survival. Furthermore, lymphoid cells from surviving vaccinated mice were capable of adoptively transferring anti-cancer immunity to naïve animals, significantly increasing their survival rates upon subsequent LLC carcinoma cell implantation. Vaccinated mice bearing LLC tumours exhibited a reduction in regulatory CD4⁺CD25⁺Foxp3⁺ T cells in the spleen, with no effect observed in the central memory CD4⁺CD44⁺CD62L⁺ T-cell compartment. Moreover, vaccinated mice displayed increased interferon gamma (IFN-γ) levels in the blood, with no significant changes in interleukin-10 (IL-10) levels. Prophylactic vaccination with xenogeneic CTAs effectively induces long-term, stable anti-cancer immunity, demonstrating potential for future immunopreventive strategies. Full article

The xeno-fungusphere, a novel microbial ecosystem formed by integrating exogenous fungi, indigenous soil microbiota, and electroactive microorganisms within microbial fuel cells (MFCs), offers a transformative approach for agricultural remediation and medicinal plant conservation. By leveraging fungal enzymatic versatility (e.g., laccases, cytochrome P450s) and conductive hyphae, this system achieves dual benefits. First, it enables efficient degradation of recalcitrant agrochemicals, such as haloxyfop-P, with a removal efficiency of 97.9% (vs. 72.4% by fungi alone) and a 27.6% reduction in activation energy. This is driven by a bioelectric field (0.2–0.5 V/cm), which enhances enzymatic activity and accelerates electron transfer. Second, it generates bioelectricity, up to 9.3 μW/cm², demonstrating real-world applicability. In medicinal plant soils, xeno-fungusphere MFCs restore soil health by stabilizing the pH, enriching dehydrogenase activity, and promoting nutrient cycling, thereby mitigating agrochemical-induced inhibition of secondary metabolite synthesis (e.g., ginsenosides, taxol). Field trials show 97.9% herbicide removal in 60 days, outperforming conventional methods. Innovations, such as adaptive electrodes, engineered strains, and phytoremediation-integrated systems, have been used to address soil and fungal limitations. This technology bridges sustainable agriculture and bioenergy recovery, offering the dual benefits of soil detoxification and enhanced crop quality. Future IoT-enabled monitoring and circular economy integration promise scalable, precision-based applications for global agroecological resilience. Full article

An experimental setup was developed, incorporating a monitored DualSun^® photovoltaic–thermal (PV/T) panel and a weather station to continuously record real-time climatic conditions. This setup enables an hour-by-hour comparison between the actual performance observed under real-world conditions and the predictions generated by the thermal model. The generated dataset was used to evaluate a thermal model derived from the literature, comparing its predictions with measured data. The model adopts a quasi-steady-state, one-dimensional approach based on heat balance equations applied to both the photovoltaic cells and the heat transfer fluid. Conducted during the summer of 2022, the experiment provides valuable insights into the accuracy of the literature-based thermal model under summer meteorological conditions. The results show a good correlation between the experimental data and the model’s predictions. The average deviation observed for the outlet fluid temperature is 0.1 °C during the day and 1.3 °C at night. Consequently, the findings underscore the model’s effectiveness for evaluating daytime performance, while also pointing out its limitations for nighttime predictions, especially when hybrid PV/T collectors are used for applications such as nighttime free cooling. Full article

Lentiviral vectors (LVs) have become a fundamental tool in gene therapy due to their unique ability to transduce both dividing and non-dividing cells, transfer large genes of up to 10 kb, and facilitate stable, long-term expression of therapeutic genes into target cells. A key application of LVs is the ex vivo genetic modification of patient-derived cells, such as the production of CAR-T cells by transducing isolated T cells with LVs to express the CAR gene, enabling them to target and destroy cancer cells once infused back into the patient. However, these ex vivo gene therapy drugs are often dismally unaffordable due to the complex procedures involved, including cell isolation, genetic modification, and expansion, along with the significant risks associated with immune conditioning to ensure successful engraftment. To overcome these barriers, direct in vivo transgene delivery to physiologically relevant cells has been explored, bypassing the need for ex vivo manipulations and reducing costs. Yet, a major challenge in this approach is engineering LV cell tropism to ensure the precise targeting of specific cells while avoiding off-target effects. Recent advances in modifying LV surface proteins have shown promise, including the successful in vivo generation of CAR T cells and ensuing clinical trials. This review is aimed at providing an up-to-date account of the progress in engineering LV tropism, covering the utility of different heterologous viral envelopes and their engineering to achieve cell-type-specific delivery and host immune evasion, and highlighting the potential of in vivo gene therapy to improve the affordability and accessibility of life-saving treatments. Full article

Cases of new COVID-19 infection, which manifested in 2019 and caused a global socioeconomic crisis, still continue to be registered worldwide. The high mutational activity of SARS-CoV-2 leads to the emergence of new antigenic variants of the virus, which significantly reduces the effectiveness of COVID-19 vaccines, as well as the sensitivity of diagnostic test systems based on variable viral antigens. These problems may be solved by focusing on highly conserved coronavirus antigens, for example nucleocapsid (N) protein, which is actively expressed by coronavirus-infected cells and serves as a target for the production of virus-specific antibodies and T cell responses. It is known that anti-N antibodies are non-neutralizing, but their protective potential and functional activity are not sufficiently studied. Here, the protective effect of anti-N antibodies was studied in Syrian hamsters passively immunized with polyclonal sera raised to N(B.1) recombinant protein. The animals were infected with 10⁵ or 10⁴ TCID₅₀ of SARS-CoV-2 (B.1, Wuhan or BA.2.86.1.1.18, Omicron) 6 h after serum passive transfer, and protection was assessed by weight loss, clinical manifestation of disease, viral titers in the respiratory tract, as well as by the histopathological evaluation of lung tissues. The functional activity of anti-N(B.1) antibodies was evaluated by complement-dependent cytotoxicity (CDC) and antibody-dependent cytotoxicity (ADCC) assays. The protection of anti-N antibodies was evident only against a lower dose of SARS-CoV-2 (B.1) challenge, whereas almost no protection was revealed against BA.2.86.1.1.18 variant. Anti-N(B.1) monoclonal antibodies were able to stimulate both CDC and ADCC. Thus, anti-N(B.1) antibodies possess protective activity against homologous challenge infection, which is possibly mediated by innate Fc-mediated immune reactions. These data may be informative for the development of N-based broadly protective COVID-19 vaccines. Full article