Search Results (56)

Mercury pollution from artisanal and small-scale gold mining remains one of the most persistent environmental threats due to the high toxicity, mobility, and bioaccumulation of Hg(II). In this work, Colombian banana pseudostem waste is valorized into a lignocellulosic carbocatalyst through pyrolysis at 500 °C followed by MnCO₃-derived MnOx functionalization, producing a sustainable material for Hg(II) remediation. The transformation of the biomass leads from a fibrous structure (~25 µm) to a pyrolyzed carbon matrix (9.56 µm), and finally to a heterogeneous Mn-modified system with bimodal particle distribution (~25 µm and ~0.85 µm), the latter being associated with highly dispersed MnOx redox-active domains. Structural and textural analyses reveal that Mn incorporation significantly enhances surface properties, increasing the BET surface area from 140.8 to 213 m² g⁻¹ while reducing pore size to the meso–microporous range (~1.9 nm). Importantly, the material retains intrinsic minerals such as Ca, Mg, K, and Si, which contribute to surface basicity and ion-exchange capacity, supporting additional Hg(II) interaction pathways. Optical and electronic characterization shows a wide band gap semiconductor behavior (≈3.4 eV) and a conduction band position at −0.892 V vs. NHE, sufficiently negative to thermodynamically drive Hg²⁺ reduction to Hg⁰ under UV-A irradiation. Hg(II) quantification was validated using a UV–Vis method based on the Hg²⁺–dipicolinic acid (DPA) complex, confirming stable complex formation with 1:2 stoichiometry (Hg²⁺:DPA) and high analytical reliability (R² = 0.948, LOD = 1.85 mg L⁻¹). Photocatalytic experiments demonstrated negligible Hg(II) reduction under UV-A light in the absence of catalyst, whereas the carbon-based materials enabled significant Hg transformation through adsorption-assisted photoinduced electron transfer. Electrochemical analyses (Rct ≈ 11 Ω) confirmed efficient charge transport, while cyclic voltammetry evidenced reversible Mn(IV)/Mn(III)/Mn(II) redox cycling, which sustains electron mediation during photocatalysis. Overall, pristine biochar acts primarily through adsorption driven by oxygenated functional groups and porous structure, whereas Mn-functionalized biochar operates via a synergistic adsorption–photocatalytic mechanism. In this system, MnOx species function as redox-active centers that facilitate electron transfer from the carbon matrix to Hg(II), while the conductive lignocellulosic-derived framework enhances charge mobility. The combination of structural carbon stability, dispersed Mn active sites, and inherent mineral functionality establishes a highly efficient and sustainable carbocatalyst, demonstrating a green and scalable approach for mercury remediation in mining-impacted regions. Full article

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which persistence of immunological memory underlies disease recurrence and progression toward atopic comorbidities. Evidence indicates that pathogenic tissue-resident memory T cells (TRM), including Th2- and Th22-skewed subsets, among others, persist in both lesional and clinically resolved skin and rapidly re-initiate inflammation through production of IL-4, IL-13, IL-22 and IL-31, promoting barrier dysfunction and pruritus. In parallel, circulating CLA⁺ memory T cells retain skin-homing capacity and contribute to flare reactivation, while IgG1⁺CD23 IL-4Rα⁺ type-2 memory B cells (MBC2) constitute a reservoir for high-affinity IgE production, linking cutaneous inflammation with allergic comorbidities. These adaptive memory compartments are sustained by epithelial alarmins, dendritic cell–derived chemokines such as CCL17, CCL22 and CCL18, and the OX40/OX40L costimulatory pathway, which promotes differentiation, survival and tissue retention of memory T cells. Clinical and transcriptomic studies show how, although IL-4/IL-13 blockade reduces circulating type-2 responses, Th2A cells, Tc2 cells and activated dendritic cells can persist in clinically resolved skin, providing a mechanistic basis for relapse after treatment withdrawal. Together, these findings support the relevance of targeting memory-imprinting pathways as a promising mechanism to achieve durable disease modification in AD. Full article

Bismuth oxychloride (BiOCl)– copper oxide (CuO) heterostructures were synthesized via a solvothermal route and assessed as visible-light-driven photocatalysts for methyl orange (MO) degradation. Different CuO loadings deposited on BiOCl microspheres were investigated to identify the optimal composition. Structural and physicochemical characterization revealed that low CuO content (0.6 wt. %) promoted uniform dispersion and enhanced surface area, whereas higher loadings led to nonuniform coverage and reduced photocatalytic efficiency. Operating conditions were optimized using response surface methodology based on a central composite design, considering catalyst dosage (0.1–0.8 g L⁻¹) and pH (4–9). The highest degradation efficiency (~50% after 60 min irradiation) was achieved at pH = 4 and a catalyst dosage of 0.8 g L⁻¹ using the BiOCl surface modified with 0.6% CuO. Kinetic analysis followed a pseudo-first-order model. Mass spectrometry identified transient intermediates associated with demethylation and desulfonation pathways, while radical scavenger experiments confirmed hydroxyl radicals (^•OH) as the dominant oxidizing species, with a secondary contribution from superoxide radicals (^•O₂⁻). These results highlight the critical role of CuO dispersion and interfacial quality in enhancing charge separation and photocatalytic performance, providing practical guidelines for the rational design of BiOX-CuO heterostructures for water remediation applications. Full article

In type 1 diabetes (T1D) in non-obese diabetic (NOD) mice, dendritic cells (DCs) exhibit a Stat5b mutation that impairs regulatory T cell (Tregs) numbers and suppressive function. To correct this defect, we generated transgenic NOD mice expressing constitutively active Stat5b (NOD.Stat5b-CA) in DCs, which conferred protection from diabetes that was associated with an expanded Treg population and a marked reduction in CD8⁺ T cell frequencies in secondary lymphoid organs. However, the phenotypic characteristics and underlying mechanisms to eliminate CD8⁺ T cells in NOD.Stat5b-CA mice are unknown. In this study, we found that the frequency of Tregs was significantly higher in the thymus and peripheral lymphoid organs of NOD.Stat5b-CA mice compared with NOD mice. Tregs in the peripheral lymphoid organs exhibited increased expression of activation markers CD69 and OX40, alongside reduced CD62L. We also found that CD8⁺ T cell frequencies were reduced in the peripheral organs but not in the thymus of NOD.Stat5b-CA mice, while CD4⁺ T cell frequencies remained unchanged across all organs. Furthermore, NOD.Stat5b-CA mice exhibited a reduced frequency of central Tregs (CD62L^high CD44^low) and increased frequency of effector Tregs (CD62L^low CD44^high) under steady-state conditions compared to NOD mice. Notably, Tregs from NOD.Stat5b-CA mice displayed enhanced cytotoxic activity, evidenced by increased expression of perforin, granzyme B, and Fas ligand, potentially mediating CD8⁺ T cell frequency reduction. Collectively, these findings highlight a novel role for Stat5b-CA.DC-educated Tregs in modulating immune responses by eliminating peripheral pathogenic CD8⁺ T cells via cytotoxic pathways, thereby contributing to immune regulation in NOD.Stat5b-CA mice. Full article

Black nightshade (Solanum nigrum L.) is a highly invasive weed in agricultural systems, primarily dispersed by seeds. Its germination is regulated by temperature, which varies among populations. We investigated the germination responses to temperature in two S. nigrum populations (XJ1600 and XJ1633) and identified eight putative candidate genes: GA20ox1, GA3ox1, GA2ox1, NCED9, CYP707A2, SPT, PIF1, and ABI5. These genes are involved in the phytohormone signaling pathway. Under low-temperature conditions, SPT likely perceives cold signals, promoting germination by up-regulating GA20ox1 and CYP707A2 while suppressing GA2ox1, thus potentially increasing bioactive GAs and reducing ABA levels. Under high-temperature conditions, PIFs likely perceive the heat signal. Through regulation mediated by the known negative regulator SOMNUS (SOM), NCED9 and GA2ox1 were up-regulated, while GA3ox1 was down-regulated, which could collectively modulate seed germination by altering ABA and GA levels. This study clarifies how temperature regulates S. nigrum seed germination through integrated hormonal and genetic mechanisms. This understanding directly supports the development of predictive models for weed emergence and informs the design of sustainable control strategies. Full article

The retinal pigment epithelium (RPE) is strongly involved in the pathogenesis of several retinal diseases, such as age-related macular degeneration (AMD). RPE models addressing specific pathological pathways are of high importance for understanding cellular pathomechanisms and pre-clinical screening of potential new therapeutics. The goal of this study is to establish standard operation protocols for single-eye porcine RPE preparation for AMD-relevant models of oxidative stress (RPE-Ox) and inflammation (RPE-Inf). Porcine primary RPE were prepared from one eye and seeded into one well of 12-well plates or, for polar differentiation, in transwell inserts. Different coatings (Poly-ᴅ-Lysine and laminin) and serum content of media (10%, 5%, and 1%) were tested to determine optimal culture parameters. For RPE-Ox, cells were treated with NaIO₃, CoCl₂, or erastin; cell viability (thiazolyl blue tetrazolium bromide, MTT), and gene expression (RT-qPCR) were determined. For RPE-Inf, cells were treated with lipopolysaccharide (LPS), polyinosinic/polycytidylic acid (Poly I:C), or tumor necrosis factor alpha (TNF-α); cell viability (MTT), cytokine secretion (ELISA), and gene expression (RT-qPCR) were determined. For transwell plates in RPE-Inf, cell viability (MTT), polar cytokine secretion (ELISA), gene expression (RT-qPCR), and transepithelial electrical resistance (TEER) for barrier assessment were conducted. For RPE-Ox, effective LD₅₀ could be achieved by using 24 h stimulation with 25 µm erastin, seven days after preparation in 5% serum cultures, without coating. For gene expression assessment, the use of Poly-ᴅ-Lysine is recommended. For RPE-Inf, three days of LPS stimulation (1 µg/mL) showed effective cytokine activation with 5% serum on uncoated 12-well plates. Transwell plates are not recommended for cytokine secretion assessment. It can be used for cell barrier assays in which LPS also showed effective cell barrier decrease and gene expression assays. Two specific best practice protocols for the use of porcine single-eye cultures in AMD research concerning oxidative stress and inflammation with optimized parameters were established and are provided. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder marked by intricate interplay among skin barrier dysfunction, immune dysregulation, and microbial dysbiosis. While therapeutic advancements targeting T helper 2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway have yielded promising outcomes, a significant proportion of patients still experience inadequate relief, particularly from persistent pruritus. Achieving minimal disease activity remains an unmet clinical priority and a cornerstone of effective AD management. This review provides an in-depth analysis of current therapeutic approaches and integrates findings from recent biologic studies, with a particular focus on innovative strategies under active investigation. These approaches include targeting components of the innate immune system, such as thymic stromal lymphopoietin (TSLP) and IL-1 family cytokines; the adaptive immune system, including OX40-OX40L interactions and Th17- and Th22-related cytokines; and mechanisms associated with pruritus, such as IL-31, histamine receptors, and neurokinin 1 receptor. Emerging insights underscore the transformative potential of personalized therapeutic regimens tailored to the distinct endotypes and severity of AD. Advances in deciphering the pathogenesis of AD are unlocking unprecedented opportunities for precision medicine, offering renewed hope for improved outcomes in this multifaceted and heterogeneous condition. Full article

Manganese-based oxides, particularly β-MnO₂, have emerged as promising cathode materials for aqueous zinc-ion batteries (ZIBs) due to their high theoretical capacity, low cost, and intrinsic safety. However, their sluggish reaction kinetics, limited active sites, and poor conductivity often lead to suboptimal electrochemical performance. To address these limitations, we propose a facile ethanol-mediated hydrothermal strategy to engineer rod-like β-MnO₂ nanostructures with tailored oxygen vacancies. By precisely adjusting ethanol addition (3–5 mL) during synthesis, oxygen vacancy concentrations were optimized to enhance electronic conductivity and active site exposure. The experimental results demonstrate that β-MnOx-2-5 synthesized with 5 mL of ethanol delivers an exceptional areal capacity of 4.87 mAh cm⁻² (348 mAh g⁻¹, 469.8 Wh kg⁻¹) at 200 mA cm⁻² under a high mass loading of 14 mg cm⁻². Further, a hybrid electrode combining oxygen-deficient β-MnO₂-x-3 (air-calcined) and structurally stable β-Mn₅O₈-y-3 (Ar-calcined) achieves a retained capacity of 3.9 mAh cm⁻² with stable cycling performance, achieving an optimal equilibrium between high capacity and long-term operational durability. Systematic characterizations (XPS, ESR, XANES, FT-EXAFS) confirm vacancy-induced electronic structure modulation, accelerating ion diffusion and redox kinetics. This scalable vacancy engineering approach, requiring only ethanol dosage control, presents a viable pathway toward industrial-scale ZIB applications. Full article

Carbohydrate metabolism disorders (CMDs), including prediabetes and type 2 diabetes mellitus (T2DM), are increasingly prevalent in the aging population. Oxidative stress (OxS) plays a pivotal role in CMD pathogenesis, with extracellular superoxide dismutase (SOD3) and catalase (CAT) serving as critical antioxidant defenses. Additionally, microRNAs (miR-21 and miR-30b) regulate the oxidative and inflammatory pathways, yet their roles in elderly CMD patients remain unclear. This study evaluated miR-21 and miR-30b expression alongside SOD3 and CAT plasma levels in individuals aged ≥ 65 years (n = 126) categorized into control (n = 38), prediabetes (n = 37), and T2DM (n = 51) groups. Quantitative PCR assessed miRNA expression, while ELISA measured the enzyme levels. SOD3 levels were significantly reduced in CMDs, particularly in T2DM, whereas miR-21 was upregulated. A negative correlation between SOD3 and miR-21 was strongest in T2DM, suggesting a regulatory interplay. Neither CAT levels nor miR-30b expression differed among groups. Logistic regression indicated SOD3 as a protective biomarker, with each 1 ng/mL increase reducing the CMD risk by ~5–6%. The ROC analysis supported SOD3’s diagnostic potential, while miR-21 showed a modest association. These findings highlight SOD3 downregulation and miR-21 upregulation as potential contributors to CMD progression in elderly patients, warranting further research into their mechanistic roles and therapeutic potential. Full article

Backgroung/objectives: Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of malignant lymphoma and is a heterogeneous disease with various gene and chromosomal abnormalities. The development of novel therapeutic treatments has improved DLBCL prognosis, but patients with early relapse or refractory disease have a poor outcome (with a mortality of around 40%). Metabolic reprogramming is a hallmark of cancer cells. Fatty acid (FA) metabolism is frequently altered in cancer cells and recently emerged as a critical survival path for cancer cell survival. Methods: We first performed the metabolic characterization of an extended panel of DLBCL cell lines, including lipid droplet content. Then, we investigated the effect of drugs targeting FA metabolism on DLBCL cell survival. Further, we studied how the combination of drugs targeting FA and either mitochondrial metabolism or mTOR pathway impacts on DLBCL cell death. Results: Here, we reveal, using a large panel of DLBCL cell lines characterized by their metabolic status, that targeting of FA metabolism induces massive DLBCL cell death regardless of their OxPhos or BCR/glycolytic subtype. Further, FA drives resistance of DLBCL cell death induced by mitochondrial stress upon treatment with either metformin or L-asparaginase, two FDA-approved antimetabolic drugs. Interestingly, combining inhibition of FA metabolism with that of the mTOR oncogenic pathway strongly potentiates DLBCL cell death. Conclusion: Altogether, our data highlight the central role played by FA metabolism in DLBCL cell survival, independently of their metabolic subtype, and provide the framework for the use of drugs targeting this metabolic vulnerability to overcome resistance in DLBCL patients. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, characterized by aggressive and heterogeneous tumors originating from B-cells. Especially in patients with relapsed or refractory (R/R) disease, DLBCL remains a challenging cancer to treat. Metabolic reprogramming is a hallmark of malignant cells. Our research focuses on developing strategies to enhance clinical outcomes for R/R DLBCL patients by targeting metabolic vulnerabilities. Methods: We investigated the effects of combining metformin and L-asparaginase, two FDA-approved antimetabolic drugs, on DLBCL cell metabolism and survival. Nuclear magnetic resonance (NMR) spectroscopy was employed to assess metabolic disturbances induced by the drug combination. The impact on lipid metabolism, glycolysis, glutaminolysis, the tricarboxylic acid (TCA) cycle, and antioxidant responses was examined. Induction of apoptosis was evaluated by FACS analysis. Results: The combination of metformin and L-asparaginase strongly sensitized DLBCL cells to apoptosis, independently of their oxidative phosphorylation (OxPhos) or BCR/glycolytic status. NMR spectroscopy revealed that this combination induces broader metabolic disturbances than either drug alone. It disrupts lipid metabolism by altering levels of phospholipids, cholesterol, and fatty acids. Additionally, it counteracts the pro-glycolytic effect of metformin, decreases glycolysis, and reduces glutaminolysis. It also affects the TCA cycle and antioxidant responses, critical for cellular energy production and redox balance. Furthermore, this combination interferes with two key cancer survival pathways, mTORC1 and MAPK signaling. Importantly, proof of principle for its beneficial effect was demonstrated in DLBCL patients. Conclusions: Combining metformin and L-asparaginase affects DLBCL cell survival by targeting multiple metabolic pathways and may represent a novel therapeutic approach for R/R DLBCL patients. Full article

Each cell in the human body is continually exposed to harmful external and internal factors. During evolution, cells have developed various defence systems, divided into enzymatic and non-enzymatic types, to which low-weight molecule antioxidants belong. In this article, the ionisation potential and electron affinity, as well as global reactivity descriptors of Vitamin C, Melatonin, Uric Acids, and N-acetyl-L-cysteine, were theoretically investigated at the MP-2/aug-cc-pVTZ level of theory in the condensed (aqueous) phase. The vertical ionisation potential and electron affinity are discussed in terms of non-equilibrated and equilibrated solvent–solute interactions. Additionally, at the same theoretical level, the electronic properties of canonical and oxidised derivatives of guanine were analysed. The presented results indicate that the selected antioxidants for this study (Vitamin C, Uric Acid, NAC, and Melatonin) exhibit the highest adiabatic electron affinity, while guanine derivatives (Gua, ^OXOGua, Guo, dGuo, ^OXOGuo, ^OXOdGuo) are more prone to adiabatic radical cation formation. A red-ox balance (redox homeostasis) is crucial for intracellular signalling pathways that are reactive oxygen and nitrogen species (RO/NS)-dependent. Should this gentle balance be disrupted, either by an overload or deficit of species, physiological consequences may result, which in turn lead to pathological outcomes. On the other hand, maintaining the stability of the above balance of antioxidants/radicals may result in the improved effectiveness and safety of anticancer radiotherapy/chemotherapy or combined therapies with a subsequent increase in a patient’s quality of life. Full article

Rice (Oryza sativa L.) is a main food crop in China and is crucial for the maintenance of national food security. The growth of rice seedling roots is regulated by a variety of genes and is closely related to abscisic acid (ABA) metabolism and ABA signaling pathways. In this study, we found that OsABT could increase the length of rice root tip meristem cells and upregulate root development-related genes, thereby alleviating ABA’s inhibitory effects on rice root growth and seed germination. The overexpression of OsABT reduced the ABA content by downregulating ABA synthesis genes (OsNCED3 and OsNCED5) and upregulating the ABA catabolic gene (OsABA8ox2). In addition, OsABT interacted with OsPYL4, OsPYL10, and OsABIL2 via the ABA signal transduction pathway. By inhibiting the expression of positive regulatory genes (OsPYL9 and Rab16a) and increasing the expression of a negative regulatory gene (OsABIL1), OsABT negatively regulates the ABA signal transduction pathway. Transcriptome analysis revealed that OsABT inhibited the activity of Gene Ontology entries in response to ABA. Thus, OsABT increased the length of the rice root meristem, reduced the accumulation of ABA in the roots, and negatively regulated the ABA signal transduction pathway by interacting with key proteins in this pathway, ultimately relieving the inhibitory effect of ABA on rice root length and seed germination. Full article

Several lines of evidence have linked the intestinal bacterium Helicobacter cinaedi with the pathogenesis of atherosclerosis, identifying the Cinaedi Antigen Inflammatory Protein (CAIP) as a key virulence factor. Oxidative stress and inflammation are crucial in sustaining the atherosclerotic process and oxidized LDL (oxLDL) uptake. Primary human macrophages and endothelial cells were pre-incubated with 10 µM diphenyl iodonium salt (DPI) and stimulated with 20 µg/mL CAIP. Lectin-like oxLDL receptor (LOX-1) expression was evaluated by FACS analysis, reactive oxygen species (ROS) production was measured using the fluorescent probe H2DCF-DA, and cytokine release was quantified by ELISA assay. Foam cells formation was assessed by Oil Red-O staining, and phosphorylation of p38 and ERK1/2 MAP kinases and NF-κB pathway activation were determined by Western blot. This study demonstrated that CAIP triggered LOX-1 over-expression and increased ROS production in both macrophages and endothelial cells. Blocking ROS abrogated LOX-1 expression and reduced LDL uptake and foam cells formation. Additionally, CAIP-mediated pro-inflammatory cytokine release was significantly affected by ROS inhibition. The signaling pathway induced by CAIP-induced oxidative stress led to p38 MAP kinase phosphorylation and NF-κB activation. These findings elucidate the mechanism of action of CAIP, which heightens oxidative stress and contributes to the atherosclerotic process in H. cinaedi-infected patients. Full article

Asthma is a chronic inflammatory lung disease. Refractory asthma poses a significant challenge in management due to its resistance to standard therapies. Key molecular pathways of refractory asthma include T2 inflammation mediated by Th2 and ILC2 cells, eosinophils, and cytokines including IL-4, IL-5, and IL-13. Additionally, non-T2 mechanisms involving neutrophils, macrophages, IL-1, IL-6, and IL-17 mediate a corticosteroid resistant phenotype. Mediators including alarmins (IL-25, IL-33, TSLP) and OX40L have overlap between T2 and non-T2 inflammation and may signify unique pathways of asthma inflammation. Therapies that target these pathways and mediators have proven to be effective in reducing exacerbations and improving lung function in subsets of severe asthma patients. However, there are patients with severe asthma who do not respond to approved therapies. Small molecule inhibitors, such as JAK-inhibitors, and monoclonal antibodies targeting mast cells, IL-1, IL-6, IL-33, TNFα, and OX40L are under investigation for their potential to modulate inflammation involved in refractory asthma. Understanding refractory asthma heterogeneity and identifying mediators involved are essential in developing therapeutic interventions for patients unresponsive to currently approved biologics. Further investigation is needed to develop personalized treatments based on these molecular insights to potentially offer more effective treatments for this complex disease. Full article