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Simple Summary: For the first time, we hypothesized an inverse correlation and almost mutual exclusivity between RKIP and EGFR expression in different solid tumors. In silico, cervical cancer was the third tumor type in which this inverse correlation was strong, a result that we validated in a series of 202 patient samples. Importantly, we highlight the importance of this axis by demonstrating its strong association with patient prognosis. Using in vitro functional assays, we showed that RKIP can control EGFR mRNA expression as well as its phosphorylation status, while EGFR activation can also interfere with RKIP protein expression levels. Therefore, the discovery of this novel putative RKIP/EGFR loop opens the door for several interesting future studies in many other tumor types, mainly those in which EGFR has a crucial oncogenic role. Raf Kinase Inhibitor Protein (RKIP) is recognized as a bona fide tumor suppressor gene, and its diminished expression or loss is associated with the progression and poor prognosis of various solid tumors. It exerts multifaceted roles in carcinogenesis by modulating diverse intracellular signaling pathways, including those governed by HER receptors such as MAPK. Given the significance of HER receptor overexpression in numerous tumor types, we investigated the potential oncogenic relationship between RKIP and HER receptors in solid tumors. Through a comprehensive in silico analysis of 30 TCGA PanCancer Atlas studies encompassing solid tumors (10,719 samples), we uncovered compelling evidence of an inverse correlation between RKIP and EGFR expression in solid tumors observed in 25 out of 30 studies. Conversely, a predominantly positive association was noted for the other HER receptors (ERBB2, ERBB3, and ERBB4). In particular, cervical cancer (CC) emerged as a tumor type exhibiting a robust inverse association between RKIP and EGFR expression, a finding that was further validated in a cohort of 202 patient samples. Subsequent in vitro experiments involving pharmacological and genetic modulation of EGFR and RKIP showed that RKIP depletion led to significant upregulation of EGFR mRNA levels and induction of EGFR phosphorylation. Conversely, EGFR overactivation decreased RKIP expression in CC cell lines. Additionally, we identified a common molecular signature among patients depicting low RKIP and high EGFR expression and demonstrated the prognostic value of this inverse correlation in CC patients. In conclusion, our findings reveal an inverse association between RKIP and EGFR expression across various solid tumors, shedding new light on the underlying molecular mechanisms contributing to the aggressive phenotype associated with RKIP and EGFR in cervical cancer. [ABSTRACT FROM AUTHOR]

The widespread adoption of digital technologies in educational systems has been globally reflecting a shift in pedagogic content delivery that seems to fit modern generations of students while tackling relevant challenges faced by the current scholar context, e.g., progress traceability, pedagogic content fair access and intuitive visual representativeness, mobility issue mitigation, and sustainability in crisis situations. Among these technologies, augmented reality (AR) emerges as a particularly promising approach, allowing the visualization of computer-generated interactive data on top of real-world elements, thus enhancing comprehension and intuition regarding educational content, often in mobile settings. While the application of AR to education has been widely addressed, issues related to performance interaction and cognitive performance are commonly addressed, with lesser attention paid to the limitations associated with setup complexity, mostly related to experiences configurating tools, or contextual range, i.e., technical/scientific domain targeting versatility. Therefore, this paper introduces ARPocketLab, a digital, mobile, flexible, and scalable solution designed for the dynamic needs of modern tutorship. With a dual-interface system, it allows both educators and students to interactively design and engage with AR content directly tied to educational outcomes. Moreover, ARPocketLab's design, aimed at handheld operationalization using a minimal set of physical resources, is particularly relevant in environments where educational materials are scarce or in situations where remote learning becomes necessary. Its versatility stems from the fact that it only requires a marker or a surface (e.g., a table) to function at full capacity. To evaluate the solution, tests were conducted with 8th-grade Portuguese students within the context of Physics and Chemistry subject. Results demonstrate the application's effectiveness in providing didactic assistance, with positive feedback not only in terms of usability but also regarding learning performance. The participants also reported openness for the adoption of AR in pedagogic contexts. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efficacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy. Its combination with chemotherapy has significantly improved therapeutic outcomes. In line with this, our team has developed temozolomide–transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes that were revealed to be biocompatible with non-cancerous cells and in a zebrafish model and were able to efficiently target and internalize into SNB19 and U373 glioma cell lines. The transfection of these cells, mediated by the formulated peptide-drug/gene complexes, resulted in p53 expression. The combined action of the anticancer drug with p53 supplementation in cancer cells enhances cytotoxicity, which was correlated to apoptosis activation through quantification of caspase-3 activity. In addition, increased caspase-9 levels revealed that the intrinsic or mitochondrial pathway of apoptosis was implicated. This assumption was further evidenced by the presence, in glioma cells, of Bax protein overexpression—a core regulator of this apoptotic pathway. Our findings demonstrated the great potential of peptide TMZ/p53 co-delivery complexes for cellular transfection, p53 expression, and apoptosis induction, holding promising therapeutic value toward glioblastoma. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that preen oil acts to reduce or eliminate feather‐associated bacteria. The mechanisms underlying this antibacterial activity, however, are incompletely understood. In addition to the activity of alcohols (i.e. 3,7‐dimethyloctan‐1‐ol), recent research has suggested that antimicrobial peptides may underlie the antibacterial activity of preen oil. Here, we document the presence of innate and adaptive immune proteins, lysozyme and immunoglobulin Y (IgY), in the preen oil of house sparrows Passer domesticus. We suggest lysozyme functions as an antimicrobial agent, with potentially important impacts against Gram‐positive feather degrading bacteria. Furthermore, both lysozyme and IgY likely act in local immune defence of the preen gland, and may also play a role in regulating the local microbiome, with potentially important consequences for chemical communication and signalling. Our findings suggest that the preen gland and its secretions should be considered an integral part of the body's first line of defence against invading infections. [ABSTRACT FROM AUTHOR]

We assessed whether ecophysiological requirements are consistent with the environmental traits within the current ranges in a relictual lizard group, Algyroides, composed of four species with restricted and disjunctive distributions. We considered temperature, precipitation and their seasonal profiles, and focused on the preferred body temperature (Tp) and the evaporative water loss (EWL). The ranges of all four species differed in environmental traits. The two geographically more restricted species followed divergent patterns: A. moreoticus inhabits hot and climatically buffered areas, and A. marchi occupies cold seasonal environments. Tp and EWL also differed among species following a geographical grouping: A. nigropunctatus (Slovenia) and A. fitzingeri (Sardinia) selected for lower Tp and lost less water than the southern species A. moreoticus (Peloponnese) and A. marchi (Southern Spain). Tp and EWL were correlated at species level but not at individual level within species. Results suggest that the current distribution of Algyroides species partly reflects their ecophysiology, with water ecology taking precedence over thermal ecology as constraining factor. By unravelling the environmental factors limiting the distribution of species, ecophysiology may provide directions for conservation, predicting the degree of vulnerability to climate change. [ABSTRACT FROM AUTHOR]

Raf kinase inhibitor protein (RKIP), an important modulator of intracellular signalling pathways, is commonly downregulated in multiple cancers. This reduction, or loss of expression, is correlated not only with the presence of metastasis, contributing to RKIP's classification as a metastasis suppressor, but also with tumour aggressiveness and poor prognosis. Recent findings suggest a strong involvement of RKIP in the modulation of tumour microenvironment components, particularly by controlling the infiltration of specific immune cells and secretion of pro-metastatic factors. Additionally, RKIP interaction with multiple signalling molecules seems to potentiate its function as a regulator of inflammatory processes, mainly through stimulation of anti- or pro-inflammatory cytokines. Furthermore, RKIP is involved in the modulation of immunotherapeutic drugs response, through diverse mechanisms that sensitize cells to apoptosis. In the present review, we will provide updated information about the role of RKIP as an inflammatory and immune modulator and its potential implications in cancer will be addressed. [ABSTRACT FROM AUTHOR]

Lung cancer is the most deadly neoplasm with the highest incidence in both genders, with non-small cell lung cancer (NSCLC) being the most frequent subtype. Somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are key drivers of NSCLC progression, with EGFR inhibitors being particularly beneficial for patients carrying the so-called "EGFR-sensitizing mutations". However, patients eventually acquire resistance to these EGFR inhibitors, and a better knowledge of other driven and targetable proteins will allow the design of increasingly accurate drugs against patients' specific molecular aberrations. Raf kinase inhibitory protein (RKIP) is an important modulator of relevant intracellular signaling pathways, including those controlled by EGFR, such as MAPK. It has been reported that it has metastasis suppressor activity and a prognostic role in several solid tumors, including lung cancer. In the present review, the potential use of RKIP in the clinic as a prognostic biomarker and predictor of therapy response in lung cancer is addressed. [ABSTRACT FROM AUTHOR]

Layered double hydroxides (LDHs) are stimuli-responsive anionic nanoclays. The vast possibilities of using LDHs can lead to their existence in the ecosystem, raising a question of potential ecological concern. However, little is known about the effect of these nanomaterials on freshwater organisms. The present study aimed to assess the ecotoxicological effects of Zinc-Aluminium LDH-nitrate (ZnAl LDH-NO 3 ) in zebrafish (Danio rerio) early life stages. The endpoints measured were mortality, malformations and hatching rate after exposure of D. rerio embryos and larvae to ZnAl LDH-NO 3 following the OECD 236 guideline. The behavioral, biochemical (markers of oxidative stress and neurotoxicity), and molecular (at DNA level) alterations were also assessed using sub-lethal concentrations. No observable acute effects were detected up to 415.2 mg LDH/L while the 96 h-LC 50 was estimated as 559.9 mg/L. Tested LDH caused malformations in D. rerio embryos, such as pericardial edema, incomplete yolk sac absorption and tail deformities (96 h-EC 50  = 172.4 mg/L). During the dark periods, the locomotor behavior in zebrafish larvae was affected upon ZnAl LDH-NO 3 exposure. However, no significant biochemical and molecular changes were recorded. The present findings suggest that ZnAl LDH-NO 3 can be regarded as a non-toxic nanomaterial towards D. rerio (E/LC 50 > > 100 mg/L) although impairment of the locomotion behavior on zebrafish embryos can be expected at concentrations below 100 mg/L., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Anti-VEGF therapy with Bevacizumab is approved for glioblastoma treatment, however, it is known that tumors acquired resistance and eventually became even more aggressive and infiltrative after treatment. In the present study we aimed to unravel the potential cellular mechanisms of resistance to Bevacizumab in glioblastoma in vitro models. Using a panel of glioblastoma cell lines we found that Bevacizumab is able to block the secreted VEGF by the tumor cells and be internalized to the cytoplasm, inducing cytotoxicity in vitro . We further found that Bevacizumab increases the expression of hypoxic (HIF-1α and CAIX) and glycolytic markers (GLUT1 and MCT1), leading to higher glucose uptake and lactate production. Furthermore, we showed that part of the consumed glucose by the tumor cells can be stored as glycogen, hampering cell dead following Bevacizumab treatment. Importantly, we found that this change on the glycolytic metabolism occurs independently of hypoxia and before mitochondrial impairment or autophagy induction. Finally, the combination of Bevacizumab with glucose uptake inhibitors decreased in vivo tumor growth and angiogenesis and shift the expression of glycolytic proteins. In conclusion, we reported that Bevacizumab is able to increase the glucose metabolism on cancer cells by abrogating autocrine VEGF in vitro . Define the effects of anti-angiogenic drugs at the cellular level can allow us to discover ways to revert acquired resistance to this therapeutic approaches in the future., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-α-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare.