Search Results (1,876)

Background: This study aimed to investigate the impact of the diabetic environment on the development of experimental autoimmune uveoretinitis (EAU) and the activation status of microglia in the eye. Methods: EAU was induced in wild-type (WT) and streptozotocin (STZ)-induced diabetic mice (STZ-EAU mice). Disease severity was assessed using funduscopy, optical coherence tomography (OCT), and histopathological analysis. The proportions of Th1, Th17, and regulatory T cells in the spleen were analyzed by flow cytometry. Retinal microglia were quantified using immunohistochemistry. To further characterize retinal cell populations and gene expression profiles, single-cell RNA sequencing (scRNA-seq) was performed. Results: STZ-EAU mice exhibited significant reductions in both the incidence and severity of EAU compared with WT-EAU mice. These were accompanied by a decreased proportion of Th1 cells, which are crucial for EAU pathogenesis, in the spleens of STZ-EAU mice. Retinal microglial accumulation was markedly reduced in STZ-EAU mice compared with WT-EAU mice. scRNA-seq analysis revealed a significant change in the microglial phenotype in STZ-EAU mice, characterized by decreased expression of MHC class I/II and the suppression of antigen presentation signaling pathways. Activated microglia in STZ-EAU mice showed reduced gene expression of M1 markers (CD68, CD74, and IL1B) and increased gene expression of M2 markers (MSR1, CD163, and MRC1), suggesting a shift toward an anti-inflammatory M2 phenotype. Conclusions: EAU is suppressed in STZ-induced diabetic mice, likely due to alterations in microglial polarization toward an M2 phenotype. These results suggest a decrease in T cell responses to pathogens in a diabetic environment, which could be one of the underlying factors for the increased susceptibility to infection in diabetic patients. Inhibiting the M2 polarization of microglia may reduce the susceptibility to infection in patients with diabetes. Full article

The giant squid (Dosidicus gigas) is an abundant marine species with high protein content, making it a promising resource for the food and biomaterial industries. This study aimed to investigate the effect of temperature (25–100 °C) on the structural changes in sarcoplasmic, myofibrillar, and stromal proteins isolated from squid mantle. Fourier-transform infrared spectroscopy (FT-IR) and circular dichroism (CD) were employed to monitor modifications in secondary structure, while field emission scanning electron microscopy (FE-SEM) was used to examine morphological characteristics. The FT-IR analysis revealed temperature-induced transitions in amide I, II, and A bands, indicating unfolding and aggregation processes, particularly in myofibrillar and stromal proteins. CD results confirmed a loss of α-helix content and an increase in β-sheet structures with rising temperature, especially above 60 °C, suggesting progressive denaturation. FE-SEM micrographs illustrated clear morphological differences: sarcoplasmic proteins displayed smooth, amorphous structures; myofibrillar proteins exhibited fibrous, porous networks; and stromal proteins presented dense and layered morphologies. These findings highlight the different thermal sensitivities and structural behaviors of squid muscle proteins and provide insight into their potential functional applications in thermally processed foods and bio-based materials. Full article

Background/Objectives: This study aimed to translate the Child Coeliac Disease Food Attitudes and Behaviours Scale (Child CD-FAB) into Brazilian Portuguese and to evaluate its reproducibility and internal consistency. Methods: Three steps were carried out: (i) translation and cultural adaptation of the Child CD-FAB into Brazilian Portuguese; (ii) pre-test; and (iii) psychometric evaluation of the Child CD-FAB-BR. The Child CD-FAB was translated and back-translated, and then discussed with and approved by the author of the original instrument. The translated version was tested on five children and adolescents (aged 8 to 16 years) with coeliac disease to assess comprehension. Subsequently, psychometric evaluation used responses from 20 participants with the same characteristics, assessing reproducibility (test–retest reliability) via intraclass correlation coefficient (ICC) and internal consistency via Cronbach’s alpha. Results: The Child CD-FAB was successfully translated to Brazilian Portuguese (Child CD-FAB-BR), and it presented good internal consistency (α = 0.892) and an excellent intraclass correlation coefficient (ICC = 0.923). Conclusions: The Child CD-FAB-BR is the first instrument to evaluate food attitudes and behaviours in Brazilian children and adolescents with CD, showing good psychometric properties. This instrument will support future research and clinical practice by guiding behaviour-based strategies to enhance nutritional education and public policies for this group. Full article

The state of the art in the thermodynamics of calix[4]resorcinarene derivatives and its metal ion complexes is briefly discussed in the introduction. This is followed by the synthesis and characterization of a recyclable calix[4]resorcinarene amide derivative (L). The 1H NMR analyses in CD3CN and CD3OD showed solvent-dependent conformational changes with a notable downfield chemical shift in the aromatic proton (H-2) in moving from deuterated methanol to acetonitrile, indicating an interaction of the solvent within the ligand cavity as suggested by molecular dynamic simulations. 1H NMR complexation in acetonitrile revealed that L forms relatively strong 1:1 complexes with cations, with selectivity for Ca(II) and, to lesser extent, with Pb(II) over other metal cations. The composition of the complexes is corroborated by conductance measurements. The thermodynamics of these systems indicate that the complexation process is predominantly enthalpy controlled in acetonitrile, while it is entropy controlled in methanol. A remarkable outcome of fundamental studies is found in its application as new material for the removal of Ca(II) from water. The capacity of L to remove Ca(II) from water is 24 mmol/g which exceeds by far the capacity of cation exchange resins. Full article

Oncolytic herpes simplex virus (oHSV) is a promising cancer immunotherapy that induces tumor cell lysis and stimulates anti-tumor immunity. Our previous single-cell RNA sequencing analysis of oHSV-treated medulloblastoma tumors revealed expansion and activation of tumor-infiltrating dendritic cells (DCs), and direct oHSV infection of DCs within the brain. While the therapeutic effects of oHSVs have been primarily attributed to tumor cell infection, we hypothesize that direct infection of DCs also contributes to therapeutic efficacy by promoting DC maturation and immune activation. Although the oHSV infection in DCs was abortive, it led to increased expression of major histocompatibility complex (MHC) class I/II and co-stimulatory molecules. oHSV-infected DCs activated naïve CD4⁺ and CD8⁺ T cells, inducing expression of CD69 and CD25. These primed T cells exhibited enhanced cytotoxicity against CT-2A glioma cells. Adoptive transfer of oHSV-infected DCs via subcutaneous injection near inguinal lymph nodes delayed tumor growth in a syngeneic CT-2A glioma model, independent of tumor viral replication and lysis. Mechanistically, our in vitro studies demonstrate that oHSV can directly infect and functionally activate DCs, enabling them to prime effective anti-tumor T cell responses. This study highlights the anti-tumor potential of leveraging oHSV-infected DCs to augment viroimmunotherapy as a cancer therapeutic. Full article

Goethite, a ubiquitous Fe(III) oxyhydroxide mineral, typically occurs in very small particle sizes whose interfacial properties critically influence the fate and transport of ionic species in natural systems. The surface site density of synthetic goethite increases with particle size, resulting in enhanced adsorption capacity per unit area. In the first two parts of this study, we modeled the adsorption of protons, nitrate, As(V), Pb(II), Zn(II), and phosphate on goethite as a function of particle size, adsorbate concentration, pH, and ionic strength, using unified parameters within the CD-MUSIC framework. Here, we extend this work to characterize the interfacial behavior of carbonate in goethite suspensions, using a comprehensive dataset generated previously under both closed and open CO₂ system conditions. Carbonate oxyanions, prevalent in geochemical environments, exhibit competitive and complexation interactions with other ions and mineral surfaces. Although a bidentate bridging surface carbonate complex has been successful in previous modeling efforts on goethite, we found that the size of the carbonate moiety is too small and would require extreme octahedron bending of the goethite’s singly coordinated sites to accommodate this type of binding. Here, we propose a novel complex configuration that considers structural, physicochemical, and spectroscopic evidence. Optimal unified affinity constants and charge distribution parameters for this complex simulated all experimental data successfully, providing further validation of the CD-MUSIC model for describing relevant goethite/aqueous interfacial reactions. Full article

This three-year study evaluated the effects of various soil amendments on growth parameters and heavy metal (HM) accumulation in above- and belowground biomass of Miscanthus x giganteus (MxG), assessing its phytoremediation potential. A randomised complete block design included four treatments: I—control, II—sludge, III—mycorrhiza, and IV—MxG ash. All experimental pots were filled with soil spiked with Cd (100 mg kg⁻¹) and Hg (20 mg kg⁻¹). Aboveground biomass yield ranged from 3.44 to 5.59 t_DM ha⁻¹, with Cd and Hg concentrations in biomass varying from 5.98 to 14.62 mg Cd kg⁻¹ and 41.8 to 383.9 μg Hg kg⁻¹, respectively. Belowground biomass mass ranged from 6.90 to 8.30 t_DM ha⁻¹, with Cd and Hg concentrations between 44.3 and 57.2 mg Cd kg⁻¹ and 4.24 to 6.05 mg Hg kg⁻¹, respectively. Enrichment coefficients (EC) in aboveground biomass ranged from 0.060 to 0.146 for Cd and 0.002 to 0.019 for Hg. Belowground biomass EC values ranged from 0.44 to 0.57 for Cd and 0.21 to 0.30 for Hg. The translocation factor (TF) varied from 0.104 to 0.145 for Cd and 0.008 to 0.024 for Hg. Our findings suggest that miscanthus is more effective for heavy metal phytostabilisation and biomass production in moderately contaminated soils than for phytoextraction. Full article

T lymphocytes in human skin play essential roles in immune surveillance and tissue homeostasis, with distinct populations residing in the epidermal and dermal compartments. To characterize the molecular basis of their compartmentalized functional specialization, we performed proteomic analysis of total T cell populations isolated from healthy human skin, combining flow cytometry and liquid chromatography–tandem mass spectrometry. We quantified 5985 proteins across epidermal and dermal T cell populations, identifying 2177 significantly differentially expressed proteins (FDR < 0.05), including 1008 with >2-fold changes. Compared with dermal T cells, epidermal T cells showed elevated intensity of tissueresidency marker CD69, co-stimulatory protein CD27, complement components (C3, C4a, and Factors B and D), and proteins involved in oxidative phosphorylation and cholesterol metabolism. Epidermal T cells also exhibited higher levels of antimicrobial S100 proteins, chemokine receptor CCR6, IL-18, and MHC class I molecules, while, in contrast, dermal T cells showed increased expression of CXCR4, IL-16, and MHC class II-related proteins. While these distinct proteomic signatures suggest compartment-specific adaptations in metabolism, immune surveillance, and antigen presentation, the results should be interpreted as exploratory, given methodological limitations. Nonetheless, this study provides a valuable molecular resource for understanding the specialization of T cells within different skin layers and offers a basis for future investigations into skin immune biology and its potential implications in disease. Full article

Background/Objectives. Women living with human immunodeficiency virus (WLWH) have a six-fold higher risk of developing cervical cancer associated with high-risk human Papillomavirus (HR-HPV) than HIV-negative women. We herein assessed HR-HPV genotype distribution and plasma levels of the cancer antigen 125 (CA-125) in WLWH in a rural town in Gabon, in Central Africa. Methods. Adult WLWH attending the local HIV outpatient center were prospectively enrolled and underwent cervical visual inspection and cervicovaginal and blood sampling. HIV RNA load and CA-125 levels were measured from plasma using the Cepheid^® Xpert^® HIV-1 Viral Load kit and BioMérieux VIDAS^® CA-125 II assay, respectively. HPV detection and genotyping were performed via a nested polymerase chain reaction (MY09/11 and GP5+/6+), followed by sequencing. Results. Fifty-eight WLWH (median age: 52 years) were enrolled. Median CD4 count was 547 cells/µL (IQR: 412.5–737.5) and HIV RNA load 4.88 Log₁₀ copies/mL (IQR: 3.79–5.49). HPV prevalence was 68.96%, with HR-HPV detected in 41.37% of women. Among HR-HPV-positive samples, 87.5% (21/24) were genotypes targeted by the Gardasil vaccine, while 12.5% (3/24) were non-vaccine types. Predominant HR-HPV types included HPV-16 (13.8%), HPV-33 (10.34%), HPV-35 (5.17%), HPV-31, and HPV-58 (3.45%). Most participants had normal cervical cytology (62.07%), and a minority (14.29%) had elevated CA-125 levels, with no correlation to cytological abnormalities. Conclusions. In the hinterland of Gabon, WLWH are facing an unsuspected yet substantial burden of cervical HR-HPV infection and a neglected risk for cervical cancer. Strengthening cervical cancer prevention through targeted HPV vaccination, sexual education, and accessible screening strategies will help in mitigating associated risk. Full article

Twenty-nine sediment samples were collected from Hurghada Bay, a highly impacted coastal area along the Northern Red Sea of Egypt, to evaluate environmental quality and human-induced effects on benthic ostracods. As potential bioindicators, benthic ostracods are highly responsive to environmental disturbances, with pollution leading to reduced abundance, lower diversity, and increased opportunistic taxa. To investigate the link between ostracod assemblages and sediment contamination, we measured the concentrations of eight heavy metals (Cu, Cd, Zn, Pb, As, Cr, Ni, and Mn) using inductively coupled plasma–atomic emission spectrometry (ICP-AES). Multivariate statistical analyses identified three distinct ostracod assemblages distributed across three station groups with varying pollution levels. Group I, associated with offshore stations, exhibited low to moderate heavy metal (HM) concentrations and high ostracod abundance and was dominated by Moosella striata, Hiltermannicythere rubrimaris, Ruggieria danielopoli, Neonesidea schulzi, and Paranesidea fracticorallcola, where the water depth and sand content are the main controlling factors. In contrast, Group II, corresponding to stations with the highest HMs and total organic matter (TOM), was dominated by pollution-tolerant species Jugosocythereis borchersi, Cyprideis torosa, Alocopocythere reticulata, and, to a lesser extent, Ghardaglaia triebeli, with reduced ostracod density and diversity. Group III, characterized by stations influenced by the mud-controlling factor, had the lowest HMs and was dominated by pollution-sensitive species Xestoleberis rhomboidei, Paranesidea fortificata, and Loxocorniculum ghardaquensis. These findings highlight the ecological risks posed by HM pollution and emphasize the urgent need for pollution mitigation strategies and continued monitoring to preserve the Red Sea’s benthic biodiversity. Full article

An advanced anodic stripping voltammetry (ASV)-based Micro Electro Mechanical System (MEMS) sensor for cadmium (Cd) detection is presented in this study, which is cost-effective and efficient for in situ water monitoring, providing a crucial early warning mechanism, streamlining environmental monitoring, and facilitating timely intervention to safeguard public health and environmental safety. The rationale behind this work is to address the critical need for an in situ monitoring system for cadmium (Cd) in freshwater sources, particularly those adjacent to agricultural fields. Cd(II) is a highly toxic heavy metal that poses a significant threat to agricultural ecosystems and human health due to its rapid bioaccumulation in plants and subsequent entry into the food chain. The developed analytic device is composed of a commercial mercury salt-modified graphite screen-printed electrode (SPE) with a custom-designed innovative polydimethylsiloxane (PDMS) flow detection cell. The flow cell was prototyped using 3D printing and replica moulding, with its design and performance validated through COMSOL Multiphysics simulations to optimize inflow conditions and ensure maximum analyte dispersion on the working electrode surface. Chemical detection was performed using square wave voltammetry, demonstrating a linear response for Cd(II) concentrations of 0 to 20 µg/L. The system exhibited robust analytical performance, enabling 25–30 daily analyses with consistent sensitivity within the Limit of Detection (LoD) set by the law of 3 µg/L. Full article

Articular cartilage (AC) has a very limited capacity for self-healing once damaged. Chondrocytes maintain AC homeostasis and are key cells in AC tissue engineering (ACTE). However, chondrocytes lose their function due to oxidative stress. Umbilical cord mesenchymal stem cells (UCMSCs) are investigated as an alternative cell source for ACTE. MSCs are known to regulate tissue regeneration through host cell modulation, largely via extracellular vesicle (EV)-mediated cell-to-cell communication. The purpose of this study was to verify whether UCMSC-derived EVs (UCMSC-EVs) enhance chondrocyte function. The mean particle sizes of the UCMSC-EVs were 79.8 ± 19.05 nm. Transmission electron microscopy (TEM) revealed that UCMSC-EVs exhibited a spherical morphology. The presence of CD9, CD63, and CD81 confirmed the identity of UCMSC-EVs, with α-tubulin undetected. UCMSC-EVs maintained chondrocyte survival, and increased chondrocyte proliferation after intake by chondrocytes. UCMSC-EVs upregulated mRNA levels of SOX-9, collagen type II (Col-II), and Aggrecan, while decreasing collagen type I (Col-I) levels. UCMSC-EVs reduced the oxidative stress of chondrocytes by reducing mitochondrial superoxide production and increasing protein levels of SOD-2 and Sirt-3 in chondrocytes. The 50 most abundant known microRNAs (miRNAs) derived from UCMSC-EVs were selected for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. GO analysis revealed enrichment in pathways associated with small GTPase-mediated signal transduction, GTPase regulatory activity, and mitochondrial matrix. The KEGG analysis indicated that these miRNAs may regulate chondrocyte function through the PI3K-Akt, MAPK, and cAMP signaling pathways. In summary, this study shows that UCMSC-EVs enhance chondrocyte function and may be applied to ACTE. Full article

B-cell lymphomas, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), evade CD4+ T-cell immunity through novel HLA class II-associated immunosuppressive mechanisms. Despite expressing surface HLA-DR, these tumors fail to activate antigen-specific CD4+ T cells, independent of co-stimulation or PD-L1 checkpoint inhibition. We identified lymphoma-secreted factors that broadly disrupt HLA class II-mediated antigen presentation in both malignant B cells and dendritic cells (DCs), silencing T-cell responses. This inhibition is allele-independent (affecting DR1, DR4, DR7) but spares HLA class I-mediated CD8+ T-cell recognition, indicating a targeted immune evasion strategy. Biochemical and mass spectrometry (MALDI-MS) analyses revealed unique low-molecular-weight peptides (693–790 Da) in BL cells, absent in normal B cells, which may mediate this suppression. Functional fractionation confirmed bioactive inhibitory fractions in lymphoma lysates, further implicating tumor-intrinsic molecules in immune escape. These findings highlight a previously unrecognized axis of B-cell lymphoma immune evasion, where secreted factors disable HLA class II function across antigen-presenting cells. Therapeutically, neutralizing these immunosuppressive molecules could restore CD4+ T-cell surveillance and enhance immunotherapies in B-cell malignancies. This work underscores the importance of HLA class II dysfunction in lymphoma progression and identifies candidate targets for reversing immune suppression. Full article

In this work, a theoretical study on the combined effects of an external electric field and a nonresonant intense laser field on the electronic properties of a quantum dot with a truncated cone shape is presented. This quantum dot was made from a type-II CdTe/CdSe heterostructure (core/shell). Using the effective mass approximation with parabolic bands and the finite element method, the Schrödinger equation was solved to analyze the confined states of electron, hole, and exciton. This study demonstrates the potential of combining nonresonant intense laser and electric fields to control confinement properties in semiconductor nanodevices, with potential applications in optoelectronics and quantum mechanics-related technologies. Full article

Although PD-1/PD-L1 inhibitors have transformed cancer immunotherapy, a substantial proportion of patients derive no clinical benefit due to resistance driven by the tumour microenvironment (TME). Transforming growth factor-β (TGF-β) is a key immunosuppressive cytokine implicated in this resistance. Several bifunctional antibodies that co-target PD-1 and TGF-β signalling have entered clinical trials and shown encouraging efficacy, but the mechanistic basis of their synergy is not fully understood. Here, we engineered 015s, a bifunctional fusion antibody that simultaneously targets murine PD-1 and TGF-β and evaluated its antitumour efficacy and mechanistic impact in pre-clinical models. Antibody 015s exhibited high affinity, dual target binding, and the effective inhibition of PD-1 and TGF-β signalling. In vivo, 015s significantly suppressed tumour growth compared with anti-mPD-1 or TGF-β receptor II (TGF-βRII) monotherapy. When combined with the CD24-targeted ADC, 015s produced even greater antitumour activity and achieved complete tumour regression. Mechanistic studies demonstrated that 015s significantly reduced tumour cell migration and invasion, reversed epithelial–mesenchymal transition (EMT), decreased microvascular density, and attenuated collagen deposition within the TME. Antibody 015s also decreased bioactive TGF-β1 and increased intratumoural IFN-γ, creating a more immunostimulatory milieu. These findings support further development of PD-1/TGF-β bifunctional antibodies for cancers with high TGF-β activity or limited response to immune checkpoint blockade. Full article