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Microneedles (MNs) are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation. This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses (PeptiCRAd), whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens. The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure, induction of immune response, and tumor eradication. The findings indicated that MN-delivered PeptiCRAd was effective in peptide presentation in vivo, leading to complete tumor rejection when mice were pre-vaccinated. A rise in the cDC1 population in the lymph nodes of the MN treated mice led to an increase in the effector memory T cells in the body. Thus, the results of this study demonstrate that the combination of MN technology with PeptiCRAd may provide a safer, more tolerable, and efficient approach to cancer immunotherapy, potentially translatable to other therapeutic applications.

Immunotherapy has emerged as a promising approach for cancer treatment, with oncolytic adenoviruses showing power as immunotherapeutic agents. In this study, we investigated the immunotherapeutic potential of an adenovirus construct expressing CXCL9, CXCL10, or IL-15 in clear cell renal cell carcinoma (ccRCC) tumor models. Our results demonstrated robust cytokine secretion upon viral treatment, suggesting effective transgene expression. Subsequent analysis using resistance-based transwell migration and microfluidic chip assays demonstrated increased T-cell migration in response to chemokine secretion by infected cells in both 2D and 3D cell models. Flow cytometry analysis revealed CXCR3 receptor expression across T-cell subsets, with the highest percentage found on CD8+ T-cells, underscoring their key role in immune cell migration. Alongside T-cells, we also detected NK-cells in the tumors of immunocompromised mice treated with cytokine-encoding adenoviruses. Furthermore, we identified potential immunogenic antigens that may enhance the efficacy and specificity of our armed oncolytic adenoviruses in ccRCC. Overall, our findings using ccRCC cell line, in vivo humanized mice, physiologically relevant PDCs in 2D and patient-derived organoids (PDOs) in 3D suggest that chemokine-armed adenoviruses hold promise for enhancing T-cell migration and improving immunotherapy outcomes in ccRCC. Our study contributes to the development of more effective ccRCC treatment strategies by elucidating immune cell infiltration and activation mechanisms within the tumor microenvironment (TME) and highlights the usefulness of PDOs for predicting clinical relevance and validating novel immunotherapeutic approaches. Overall, our research offers insights into the rational design and optimization of viral-based immunotherapies for ccRCC.

The COVID-19 pandemic strongly transformed the healthcare system in the Lombardy region (Italy), forcing a rapid reorganization of hospital structures. The emergency medical service (EMS) system and emergency departments (EDs) were among the most affected departments. Several studies have shown a change in the epidemiology of time-dependent pathologies, such as stroke, during the pandemic’s peak. However, there is little scientific evidence regarding the interpandemic phase. The regional register for ED accesses (EUOL) was analyzed, taking into consideration all accesses for stroke and stroke-like syndromes during the years 2019, 2020, and 2021. The analysis shows a significant difference in the average number of diagnoses per month [2092 vs. 1815 vs. 2015, respectively (p < 0.05)] and an increase in the percentage of transports carried out by EMS vehicles to EDs [17% vs. 25% vs. 22%, respectively (p < 0.05)]. The length of stay (LOS) increased for both discharged patients (9.0 vs. 10.1 vs. 11.2 h, respectively; p < 0.005) and hospitalized patients (7.5 vs. 9.7 vs. 10.6 h, respectively; p < 0.005). During the COVID-19 pandemic, the overall number of stroke diagnoses decreased, while the percentage of patients transported to EDs by EMS vehicles increased. Furthermore, an increased processing time in EDs was highlighted.

The COVID-19 pandemic drastically reshaped healthcare in Lombardy, Italy, notably impacting EMS and emergency departments and altering the epidemiology of time-dependent pathologies such as STEMI and OHCA. While previous studies focused on modifications during the pandemic peak, with an increase in the number of OHCA diagnoses and a reduction in the number of STEMI, little evidence exists regarding the inter-pandemic phases. We analyzed OHCA and STEMI accesses to the ED in the regional emergency department access register (EUOL) for 2019–2021. The analysis revealed a significant difference in monthly diagnosis averages. For STEMI, the change was statistically significant (F(2, 33) = 4.45, p = 0.02), while it was not for OHCA (F(2, 33) = 0.18, p = 0.83). Despite the monthly decreases, the likelihood of receiving a STEMI diagnosis increased with total accesses, OR 1.40 [95% CI 1.25–1.58, p < 0.0001]. Additionally, there was a significant increase in March 2020 discharge diagnoses for OHCA compared to March 2019, OR 3.35 [95% CI 2.88–3.90, p < 0.0001], corresponding to the first pandemic wave. Therefore, our analysis indicates that the epidemiology of STEMI and OHCA was altered during the COVID-19 pandemic.

OBJETIVO: O objetivo do estudo foi apresentar a motivação e o estado de flow em atletas brasileiras de basquetebol sub 23 em função das características sociodemográficas. MÉTODOS: O estudo foi conduzido por meio de questionários realizados com as atletas de basquetebol durante o Campeonato Brasileiro Interclubes Sub 23 no ano de 2022 em São José dos Pinhais - PR. Foram utilizadas fichas de identificação das atletas, questionários SMS-II (Sport Motivation Scale) e o FSS-2 (Escala de Estado de Flow). Para verificar a normalidade dos dados utilizou-se o teste de Shapiro-Wilk. A amostra foi composta por 75 atletas do sexo feminino, com 20,8±2,20 anos, que treinavam em média 13,4±5,47 horas semanais, e tinham em média 9,82±3,05 anos de experiência na modalidade. RESULTADOS: Os resultados demonstraram que as atletas se percebem motivadas intrinsecamente, identificando-se positivamente dentre as regulações da motivação, Regulação Intrínseca (Md=6,00), Regulação Integrada (Md=6,00) e Regulação Identificada (Md=5,67). Em relação ao estado de flow foi identificado que as atletas apresentam maiores medianas nas metas claras (Md=4,00), concentração intensa (Md=4,00) e experiência autotélica (Md=4,33). CONCLUSÃO: Conclui-se, que no contexto brasileiro de basquetebol sub-23 as atletas se encontram motivadas intrinsecamente e apresentam percepeção do estado de flow na prática da modalidade.

This study explored the impact of reduced graphene oxide (rGO) addition on the thermal properties of recycled polyamide (PARec) obtained from repurposed textile industry microfibers initially earmarked for landfill disposal. Characterization of PARec involved techniques like differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). RGO was characterized through Raman spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). Mixtures with varying rGO concentrations, such as PARec-1 (0.1% rGO), PARec-5 (0.5% rGO), and PARec-10 (1% rGO), were prepared and processed in a twin-screw extruder. SEM images at PARec show good dispersion of rGO in the polymer matrix. Thermal properties were determined via DSC and TG, revealing the presence of polyamide 6 in PARec-0 and indicating rGO's quality. Notably, PARec-10 exhibited a slight 3.8% increase in melting temperature and a 7.5% rise in crystallization temperature. These results suggest the potential for improved thermal properties with rGO incorporation. The study contributes to understanding polymer blend thermal properties and introduces an innovative, efficient polymer waste recycling method aligned with sustainability principles.

Precision agriculture techniques contribute to optimizing the use of agricultural inputs, as they consider the spatial and temporal variability in the production factors. Prescription maps of limestone and fertilizers at variable rates (VRA) can be generated using various soil sampling techniques, such as point grid sampling, cell sampling, and management zone sampling. However, low-density grid sampling often fails to capture the spatial variability in soil properties, leading to inaccurate fertilizer recommendations. Sampling techniques by cells or management zones can generate maps of better quality and at lower costs than the sampling system by degree of points with low sampling density. Thus, this study aimed to compare the accuracy of different sampling techniques for mapping soil attributes in precision agriculture. For this purpose, the following sampling techniques were used: high-density point grid sampling method, low-density point grid sampling method, cell sampling method, management zone sampling method, and conventional method (considering the mean). Six areas located in the Brazilian states of Bahia, Minas Gerais, Mato Grosso, Goias, Mato Grosso do Sul, and Sao Paulo were used. The Root-Mean-Square-Error (RMSE) method was determined for each method using cross-validation. It was concluded that the cell method generated the lowest error, followed by the high-density point grid sampling method. Management zone sampling showed a lower error compared to the low-density point grid sampling method. By comparing different sampling techniques, we demonstrate that management zone and cell grid sampling can reduce soil sampling while maintaining comparable or superior accuracy in soil attribute mapping.

Mutations in the genes ANKRD26, RUNX1, and ETV6 cause three clinically overlapping thrombocytopenias characterized by a predisposition to hematological neoplasms. The ANKRD26 gene, which encodes a protein involved in protein-protein interactions, is downregulated by RUNX1 during megakaryopoiesis. Mutations in 5′UTR of ANKRD26, leading to ANKRD26-RT, disrupt this regulation, resulting in the persistent expression of ANKRD26, which leads to impaired platelet biogenesis and an increased risk of leukemia. Although ANKRD26 and ETV6 exhibit inverse expression during megakaryopoiesis, ETV6 does not regulate the ANKRD26 expression. Hypothesizing an interplay between ETV6 and ANKRD26 through in vitro studies, we explored the interactions between the two proteins. In this study, we found that ANKRD26 interacts with ETV6 and retains it in the cytoplasm, phenocopying ETV6-RT-related mutants. We found that GPS2, a component of the NCoR complex, binds both ANKRD26 and ETV6, mediating this interaction. Furthermore, ANKRD26 overexpression deregulates ETV6 transcriptional repression, supporting a common pathogenic mechanism underlying ANKRD26-RT, FPD/AML, and ETV6-RT. Our results unveil a novel ANKRD26-ETV6-GPS2 axis, providing new insights to investigate the molecular mechanism underlying thrombocytopenias with a predisposition to myeloid neoplasms that need to be further characterized.

An experimental study on the distribution of residual stresses induced by shot peening on samples of SAE 1020 steel with pre-existing compressive stresses is presented. Two samples with similar geometries were subjected to a heat treatment to relieve stress. Then, one of the samples was subjected to a cementation process to introduce compressive residual stresses. Both samples, with and without cementation, were subjected to the same shot peening treatment. Using X-ray diffraction and electrolytic polishing to remove superficial layers, the depth-resolved residual stress distribution was obtained. It was concluded that the effect of pre-existing compressive stresses should be considered as a factor that influences the final distribution of the residual stresses induced by shot peening, namely the maximum of shot peening induced residual stresses moves closer to the surface in a sample with large initial compressive stresses and its value is greater than the maximum value for a specimen with lower initial compressive stresses.

This study aimed to analyze yield components and maize yield cultivated at different population densities in management zones (MZs) delimited based on mapping the spatial variability of the soil’s apparent electrical conductivity (ECa). The soil ECa was measured, and two MZs were subsequently delimited, one with low ECa and the other with high ECa. In each MZ, four maize sowing densities were tested: 60,000 (D1); 80,000 (D2); 100,000 (D3); and 140,000 (D4) seeds ha−1. Ear length, number of grains per ear, number of grains per row, number of rows per ear, thousand-grain weight, and yield were evaluated. The increase in sowing density in the high ECa MZ linearly reduced the values of ear diameter, number of rows per ear, number of grains per ear, and thousand-grain weight. Sowing density D3, when implemented in the low ECa MZ, showed higher values for the ear length, ear diameter, number of grains per row, number of grains per ear, and thousand-grain weight. Sowing density D2 was the one with the highest yield, regardless of the MZ where it was implemented (5628.48 kg ha−1 in the high ECa management zone and 4463.63 kg ha−1 in the low ECa).

Given the consistent release of zinc oxide (ZnO) nanoparticles into the environment, it is urgent to study their impact on plants in depth. In this study, grains of rice were treated with two different concentrations of ZnO nanoparticles (NP-ZnO, 10 and 100 mg/L), and their bulk counterpart (B-ZnO) were used to evaluate whether ZnO action could depend on particle size. To test this hypothesis, root growth and development assessment, oxidative stress parameters, indole-3-acetic acid (IAA) content and molecules/enzymes involved in IAA metabolism were analyzed. In situ localization of Zn in control and treated roots was also performed. Though Zn was visible inside root cells only following nanoparticle treatment, both materials (NP-ZnO and B-ZnO) were able to affect seedling growth and root morphology, with alteration in the concentration/pattern of localization of oxidative stress markers and with a different action depending on particle size. In addition, only ZnO supplied as bulk material induced a significant increase in both IAA concentration and lateral root density, supporting our hypothesis that bulk particles might enhance lateral root development through the rise of IAA concentration. Apparently, IAA concentration was influenced more by the activity of the catabolic peroxidases than by the protective action of phenols.

Polystyrene nanoplastics and titanium dioxide nanoparticles are widely spread in all environments, often coexisting within identical frameworks. Both these contaminants can induce negative effects on cell and plant physiology, giving concerns on their possible interaction which could increase each other’s harmful effects on plants. Despite the urgency of this issue, there is very little literature addressing it. To evaluate the potential risk of this co-contamination, lentil seeds were treated for five days with polystyrene nanoplastics and titanium dioxide nanoparticles (anatase crystalline form), alone and in co-presence. Cytological analyses, and histochemical and biochemical evaluation of oxidative stress were carried out on isolated shoots and roots. TEM analysis seemed to indicate the absence of physical/chemical interactions between the two nanomaterials. Seedlings under cotreatment showed the greatest cytotoxic and genotoxic effects and high levels of oxidative stress markers associated with growth inhibition. Even if biochemical data did not evidence significant differences between materials treated with polystyrene nanoplastics alone or in co-presence with titanium dioxide nanoparticles, histochemical analysis highlighted a different pattern of oxidative markers, suggesting a synergistic effect by the two nanomaterials. In accordance, the fluorescence signal linked to nanoplastics in root and shoot was higher under cotreatment, perhaps due to the well-known ability of titanium dioxide nanoparticles to induce root tissue damage, in this way facilitating the uptake and translocation of polystyrene nanoplastics into the plant body. In the antioxidant machinery, peroxidase activity showed a significant increase in treated roots, in particular under cotreatment, probably more associated with stress-induced lignin synthesis than with hydrogen peroxide detoxification. Present results clearly indicate the worsening by metal nanoparticles of the negative effects of nanoplastics on plants, underlining the importance of research considering the impact of cotreatments with different nanomaterials, which may better reflect the complex environmental conditions.

O objetivo deste estudo foi revisar sistematicamente a contribuição da família e da escola no desenvolvimento de habilidades para a vida (HV) no contexto de formação esportiva. As buscas foram conduzidas em sete bases de dados e por meio da pesquisa de referências. Foram seguidas as descrições do Prisma, identificando 51 estudos. Os resultados demonstraram uma predominância de investigações no Canadá e nos Estados Unidos. Os autores dos estudos têm utilizado diferentes instrumentos, variáveis e modelos teóricos para verificar a contribuição da escola e/ou da família no desenvolvimento de habilidades para a vida. Conclui-se que o envolvimento escolar e o familiar no esporte podem contribuir com a aquisição, refinamento e transferência de características que podem ser aplicadas na vida dos indivíduos. Por fim, existe a necessidade de construir instrumentos quantitativos específicos que avaliem em conjunto a contribuição da escola e da família neste processo.

Background Cancer immunotherapy relies on using the immune system to recognize and eradicate cancer cells. Adaptive immunity, which consists of mainly antigen-specific cytotoxic T cells, plays a pivotal role in controlling cancer progression. However, innate immunity is a necessary component of the cancer immune response to support an immunomodulatory state, enabling T-cell immunosurveillance.Methods Here, we elucidated and exploited innate immune cells to sustain the generation of antigen-specific T cells on the use of our cancer vaccine platform. We explored a previously developed oncolytic adenovirus (AdCab) encoding for a PD-L1 (Programmed-Death Ligand 1) checkpoint inhibitor, which consists of a PD-1 (Programmed Cell Death Protein 1) ectodomain fused to an IgG/A cross-hybrid Fc. We coated AdCab with major histocompatibility complex (MHC-I)-restricted tumor peptides, generating a vaccine platform (named PeptiCab); the latter takes advantage of viral immunogenicity, peptide cancer specificity to prime T-cell responses, and antibody-mediated effector functions.Results As proof of concept, PeptiCab was used in murine models of melanoma and colon cancer, resulting in tumor growth control and generation of systemic T-cell-mediated antitumor responses. In specific, PeptiCab was able to generate antitumor T effector memory cells able to secrete various inflammatory cytokines. Moreover, PeptiCab was able to polarize neutrophils to attain an antigen-presenting phenotype by upregulating MHC-II, CD80 and CD86 resulting in an enhanced T-cell expansion.Conclusion Our data suggest that exploiting innate immunity activates T-cell antitumor responses, enhancing the efficiency of a vaccine platform based on oncolytic adenovirus coated with MHC-I-restricted tumor peptides.

Understanding the spatial variability of factors that influence crop yield is essential to apply site-specific management. The present study aimed to evaluate apparent soil electrical conductivity (ECa) in two fields (A = rainfeed; B = central-pivot irrigation), based on delimited management zones (MZs). In each MZ, the soil density (Sd) was characterized at two soil depths, and whether the delimitation of MZs, based on the spatial variability of ECa, was able to identify regions of the field with different Sd was assessed. In general, MZs with the highest mean value of ECa also presented the highest mean values of Sd. The highest Sd values were observed in the 0.1–0.2 m layer, regardless of the studied area. Regardless of soil texture, the proposed ECa was able to detect in-field differences in Sd. The delimitation of MZs, based on the spatial variability of ECa mapping, was able to differentiate the mean values of Sd between MZ 1 (1.53 g cm−3) and MZ 2 (1.67 g cm−3) in field A, in the 0.1–0.2 m layer. A statistical difference was observed for the mean values of Sd, in MZ 1, at layer 0.1–0.2 m, when comparing the two fields: A (1.53 g cm−3) and B (1.64 g cm−3). We suggest that further studies should be carried out to confirm the efficiency of ECa in detecting the soil bulk density at different soil depths.

Somatic mosaicism appears as a recurrent phenomenon among patients suffering from Fanconi anemia (FA), but its direct prognostic significance mostly remains an open question. The clinical picture of FA mosaic subjects could indeed vary from just mild features to severe hematologic failure. Here, we illustrate the case of a proband whose FA familiarity, modest signs (absence of hematological anomalies and fertility issues), and chromosome fragility test transition to negative overtime were suggestive of somatic mosaicism. In line with this hypothesis, genetic testing on patient’s peripheral blood and buccal swab reported the presence of the only FANCA paternal variant (FANCA:c.2638C>T, p. Arg880*) and of both parental alleles (the additional FANCA:c.3164G>A, p. Arg1055Gln), respectively. Moreover, the SNP analysis performed on the same biological specimens allowed us to attribute the proband’s mosaicism status to a possible gene conversion mechanism. Our case clearly depicts the positive association between somatic mosaicism and the proband's favorable clinical course due to the occurrence of the reversion event at the hematopoietic stem cell level. Since this condition concerns only a limited subgroup of FA individuals, the accurate evaluation of the origin and extent of clonality would be key to steer clinicians toward the most appropriate therapeutic decision for their FA mosaic patients.

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.