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The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records. Among 115 individuals (45.2% girls, 83.5% IP users, 96.5% CGM users), old scars were the most common skin problem (IP users 53.1%; CGM users 66.4%), while ≥2 types of skin problems co-occurred (IP users 40.6%; CGM users 27.3%). Longer IP use was associated with a higher prevalence of skin problems (50% for IP < 1 year, 98.1%-IP 1–3 years, 100% for IP > 3 years; p < 0.001), pointing out extra attention with IP use > 1 year. No significant associations were found between skin problems and gender, age, BMI centile and glycemic parameters. Dermatological complications were common among children using IP and CGM in our center, highlighting the need for vigilant monitoring and early intervention to manage these skin-related issues effectively. [ABSTRACT FROM AUTHOR]

Malaria remains an important and challenging infectious disease, and novel antimalarials are required. Benzyl isothiocyanate (BITC), the main breakdown product of benzyl glucosinolate, is present in all parts of Tropaeolum majus L. (T. majus) and has antibacterial and antiparasitic activities. To our knowledge, there is no information on the effects of BITC against malaria. The present study evaluates the antimalarial activity of aqueous extracts of BITC and T. majus seeds, leaves, and stems. We used flow cytometry to calculate the growth inhibition (GI) percentage of the extracts and BITC against unsynchronized cultures of the chloroquine-susceptible Plasmodium falciparum 3D7 − GFP strain. Extracts and/or compounds with at least 70% GI were validated by IC50 estimation against P. falciparum 3D7 − GFP and Dd2 (chloroquine-resistant strain) unsynchronized cultures by flow cytometry, and the resistance index (RI) was determined. T. majus aqueous extracts showed some antimalarial activity that was higher in seeds than in leaves or stems. BITC's GI was comparable to chloroquine's. BITC's IC50 was similar in both strains; thus, a cross-resistance absence with aminoquinolines was found (RI < 1). BITC presented features that could open new avenues for malaria drug discovery. [ABSTRACT FROM AUTHOR]

Additive Manufacturing is a manufacturing process that consists of obtaining a three-dimensional object from the deposition of material layer by layer, unlike conventional subtractive manufacturing methods. Wire Arc Additive Manufacturing stands out for its high productivity among the Additive Manufacturing technologies for manufacturing metal parts. On the other hand, the excessive heat input promotes increased residual stress levels and the occurrence of defects, such as pores, voids, a lack of fusion, and delamination. These defects result in abnormalities during the process, such as disturbances in electrical responses. Therefore, process monitoring and the detection of defects and failures in manufactured items are of fundamental importance to ensure product quality and certify the high productivity characteristic of this process. Thus, this work aimed to characterize the effects of different contaminations on the electric arc behavior of the Wire Arc Additive Manufacturing process and the occurrence of microscopic defects in thin walls manufactured by this process. To investigate the presence of defects in the metal preforms, experimental conditions were used to promote the appearance of defects, such as the insertion of contaminants. To accomplish the electric arc behavior analysis, voltage and current temporal data were represented through histograms and cyclograms, and the arc stability was assessed based on the Vilarinho index for a short circuit. Effectively, the introduction of contaminants caused electric arc disturbances that led to the appearance of manufacturing defects, such as inclusions and porosities, observed through metallographic characterization. The results confirm that the introduction of contaminations could be identified early in the Wire Arc Additive Manufacturing process through electric arc data analysis. [ABSTRACT FROM AUTHOR]

This paper develops a methodology to estimate ship emissions using Automatic Identification System data (AIS). The methodology includes methods for AIS message decoding and ship emission estimation based on the ship's technical and operational characteristics. A novel approach for ship type identification based on the visited port terminal is described. The methodology is implemented in a computational tool, SEA (Ship Emission Assessment). First, the accuracy of the method for ship type identification is assessed and then the methodology is validated by comparing its predictions with those of two other methodologies. The tool is applied to three case studies using AIS data of maritime traffic along the Portuguese coast and in the port of Lisbon for one month. The first case study compares the estimated emissions of a ferry and a cruise ship, with the ferry emitting much less than the cruise ship. The second case study estimates the geographical distribution of emissions in the port of Lisbon, with terminals corresponding to areas with a heavier concentration of exhaust emissions. The third case study focuses on the emissions from a container ship sailing along the continental coast of Portugal, differing considerably from port traffic since it operates exclusively in cruising mode. [ABSTRACT FROM AUTHOR]

This paper presents the comprehensive state-of-the-art on the challenges that short sea shipping currently faces across the world. The concept and its relationship with coastal shipping are introduced, followed by a review of the EU policies for short sea shipping and its practical impacts in modal split. A survey of the literature on the strong and weak points of this form of transportation is carried out, aimed at explaining the difficulties in achieving relevant modal shifts from road to sea. The experience with short sea shipping across the world is described and discussed, providing a global perspective. The paper then discusses the main challenges and opportunities in this field, namely decarbonisation, autonomous navigation, and digitalization. Conclusions are drawn on the possible impact of these game changing developments in this segment of the shipping industry. [ABSTRACT FROM AUTHOR]

In fused deposition modeling (FDM), the cooling history impacts the bonding between filaments and layers. The existence of thermal gradients can cause non-homogeneous properties and localized stress points that may affect the individual filaments, resulting in distortion and detachment. Thermal analysis can aid in understanding the manufacturing flaw, providing necessary tools for the optimization of the printing trajectory. The present work is intended to deepen understanding of the thermal phenomena occurring during the extrusion of polymeric materials, aiming at more efficient three-dimensional (3D) printing methods. A one-dimensional (1D) finite differential method was implemented using MATLAB to simulate the temperature evolution of an extruded filament, and the results were compared with two-dimensional (2D) COMSOL Multiphysics simulations, and experimentally validated using infrared thermography. Acrylonitrile–butadiene–styrene (ABS) was used as a test material. The energy dissipation includes forced convection and radiation heat losses to the surrounding medium. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with few effective treatment strategies. The research on the development of new treatments is often constrained by the limitations of preclinical models, which fail to accurately replicate the disease's essential characteristics. Herein, we describe the obtention, molecular, and functional characterization of the GBM33 cell line. This cell line belongs to the GBM class according to the World Health Organization 2021 Classification of Central Nervous System Tumors, identified by methylation profiling. GBM33 expresses the astrocytic marker GFAP, as well as markers of neuronal origin commonly expressed in GBM cells, such as βIII-tubulin and neurofilament. Functional assays demonstrated an increased growth rate when compared to the U87 commercial cell line and a similar sensitivity to temozolamide. GBM33 cells retained response to serum starvation, with reduced growth and diminished activation of the Akt signaling pathway. Unlike LN-18 and LN-229 commercial cell lines, GBM33 is able to produce primary cilia upon serum starvation. In summary, the successful establishment and comprehensive characterization of this GBM cell line provide researchers with invaluable tools for studying GBM biology, identifying novel therapeutic targets, and evaluating the efficacy of potential treatments. [ABSTRACT FROM AUTHOR]

The effect of current density and bath temperature in the electroplating process on resistance to corrosion of Zn-Ni alloys was evaluated in this work. The electrolytic bath consisted of nickel sulfate, zinc sulfate, sodium sulfate, boric acid, and sodium citrate at pH 7.0. The current density was varied in the range 20–80 mA/cm2 and the bath temperature in the range 30–60 °C. Increasing, independently, the current density or the bath temperature increased the nickel content in the obtained alloy, which affected the alloy microstructure, with a predominant γ phase and cauliflower-like morphology. The nickel content in the alloys was in the range 20–42%wt. A synergistic effect between the current density and bath temperature was observed from a design of experiments and response surface models. The maximum resistance to corrosion occurred for the alloy containing 42%wt. nickel. This alloy was obtained at upper levels of current density and bath temperature, presenting a corrosion potential of −0.789 V and polarization resistance of 4136 Ω.cm2. [ABSTRACT FROM AUTHOR]

Secondary metabolites (SMs) from environmental bacteria offer viable solutions for various health and environmental challenges. Researchers are employing advanced bioinformatic tools to investigate less-explored microorganisms and unearth novel bioactive compounds. In this research area, our understanding of SMs from environmental Gram-negative bacteria lags behind that of its Gram-positive counterparts. In this regard, Pedobacter spp. have recently gained attention, not only for their role as plant growth promoters but also for their potential in producing antimicrobials. This study focuses on the genomic analysis of Pedobacter spp. to unveil the diversity of the SMs encoded in their genomes. Among the 41 genomes analyzed, a total of 233 biosynthetic gene clusters (BGCs) were identified, revealing the potential for the production of diverse SMs, including RiPPs (27%), terpenes (22%), hybrid SMs (17%), PKs (12%), NRPs (9%) and siderophores (6%). Overall, BGC distribution did not correlate with phylogenetic lineage and most of the BGCs showed no significant hits in the MIBiG database, emphasizing the uniqueness of the compounds that Pedobacter spp. can produce. Of all the species examined, P. cryoconitis and P. lusitanus stood out for having the highest number and diversity of BGCs. Focusing on their applicability and ecological functions, we investigated in greater detail the BGCs responsible for siderophore and terpenoid production in these species and their relatives. Our findings suggest that P. cryoconitis and P. lusitanus have the potential to produce novel mixtures of siderophores, involving bifunctional IucAC/AcD NIS synthetases, as well as carotenoids and squalene. This study highlights the biotechnological potential of Pedobacter spp. in medicine, agriculture and other industries, emphasizing the need for a continued exploration of its SMs and their applications. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM), also known as three-dimensional (3D) printing, allows the fabrication of complex parts, which are impossible or very expensive to produce using traditional processes. That is the case for dinnerware and artworks (stoneware, porcelain and clay-based products). After the piece is formed, the greenware is fired at high temperatures so that these pieces gain its mechanical strength and aesthetics. The conventional (gas or resistive heating elements) firing usually requires long heating cycles, presently requiring around 10 h to reach temperatures as high as 1200 °C. Searching for faster processes, 3D-printed stoneware were fired using microwave (MW) radiation. The pieces were fired within 10% of the conventional processing time. The temperature were controlled using a pyrometer and monitored using Process Temperature Control Rings (PTCRs). An error of 1.25% was calculated between the PTCR (1207 ± 15 °C) and the pyrometer (1200 °C). Microwave-fast-fired pieces show similar mechanical strength to the references and to the electrically fast-fired pieces (41, 46 and 34 (N/mm2), respectively), presenting aesthetic features closer to the reference. Total porosities of ~4%, ~5% and ~9% were determined for microwave, electrically fast-fired and reference samples. Numerical studies have shown to be essential to better understand and improve the firing process using microwave radiation. In summary, microwave heating can be employed as an alternative to stoneware conventional firing methods, not compromising the quality and features of the processed pieces, and with gains in the heating time. [ABSTRACT FROM AUTHOR]

Successful SARS-CoV-2 inactivation allows its safe use in Biosafety Level 2 facilities, and the use of the whole viral particle helps in the development of analytical methods and a more reliable immune response, contributing to the development and improvement of in vitro and in vivo assays. In order to obtain a functional product, we evaluated several inactivation protocols and observed that 0.03% beta-propiolactone for 24 h was the best condition tested, as it promoted SARS-CoV-2 inactivation above 99.99% and no cytopathic effect was visualized after five serial passages. Moreover, RT-qPCR and transmission electron microscopy revealed that RNA quantification and viral structure integrity were preserved. The antigenicity of inactivated SARS-CoV-2 was confirmed by ELISA using different Spike-neutralizing monoclonal antibodies. K18-hACE2 mice immunized with inactivated SARS-CoV-2, formulated in AddaS03TM, presented high neutralizing antibody titers, no significant weight loss, and longer survival than controls from a lethal challenge, despite RNA detection in the oropharyngeal swab, lung, and brain. This work emphasizes the importance of using different techniques to confirm viral inactivation and avoid potentially disastrous contamination. We believe that an efficiently inactivated product can be used in several applications, including the development and improvement of molecular diagnostic kits, as an antigen for antibody production as well as a control for non-clinical trials. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the relationships between coping strategies, symptoms of depression, anxiety, and stress, and satisfaction with life among Portuguese workers. A sample of 402 participants (207 male, 195 female), ranging in age from 18 to 70 years (M = 32.90, SD = 11.75), was included in the study. Participants reported varying levels of work experience, ranging from 1 to 45 years (M = 10.62, SD = 4.07). The sample encompassed diverse occupations, including arts and design (n = 28), engineering (n = 23), marketing (n = 27), administration (n = 50), transportation and logistics (n = 57), clerks (n = 63), lawyers (n = 21), factory workers (n = 20), accountant and finance (n = 41), journalism (n = 27), health care (n = 29), and others (n = 16). To examine the associations between each determinant and satisfaction with life, hierarchical multiple regression analyses were conducted. Two models were tested, with predictors entered in blocks based on theoretical and empirical considerations. The second model accounted for 52.4% of the variance in satisfaction with life (F (14, 384) = 3.884, p < 0.001, R2 = 0.27, adjusted R2 = 0.24). Depressive symptoms and stress consistently exhibited a significant association (p < 0.05) with satisfaction with life across all tested models. In terms of coping mechanisms, instrumental support reinterpretation, disengagement, and humor demonstrated a significant association with satisfaction with life (p < 0.05). The findings suggest that employing adaptive coping strategies may help mitigate symptoms of mental distress and enhance satisfaction with life. By understanding the relationships between coping strategies, mental health symptoms, and satisfaction with life, interventions can be developed to promote well-being and improve overall quality of life among Portuguese workers. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition caused by a dysregulated host response to an invading pathogen such as multidrug-resistant bacteria. Despite recent advancements, sepsis is a leading cause of morbidity and mortality, resulting in a significant global impact and burden. This condition affects all age groups, with clinical outcomes mainly depending on a timely diagnosis and appropriate early therapeutic intervention. Because of the unique features of nanosized systems, there is a growing interest in developing and designing novel solutions. Nanoscale-engineered materials allow a targeted and controlled release of bioactive agents, resulting in improved efficacy with minimal side effects. Additionally, nanoparticle-based sensors provide a quicker and more reliable alternative to conventional diagnostic methods for identifying infection and organ dysfunction. Despite recent advancements, fundamental nanotechnology principles are often presented in technical formats that presuppose advanced chemistry, physics, and engineering knowledge. Consequently, clinicians may not grasp the underlying science, hindering interdisciplinary collaborations and successful translation from bench to bedside. In this review, we abridge some of the most recent and most promising nanotechnology-based solutions for sepsis diagnosis and management using an intelligible format to stimulate a seamless collaboration between engineers, scientists, and clinicians. [ABSTRACT FROM AUTHOR]

Simple Summary: Appropriate broiler nutrition is essential to guarantee good body development and a uniform growth rate. However, broiler breeder nutrition is also key for progeny success because the development of embryos and chicks depends directly on the nutrients in the yolk. The physiological status of embryos is influenced by the nutritional status of the breeder hens, which is reported to have a significant impact on progeny quality, development, and hatchability. Although phytase levels in broiler production are already consensual, there are no studies reporting the effects of phytase supplementation for broiler breeders on their progeny. The aim of this study was to evaluate how different levels of phytase supplementation, including superdosing, influence the performance and growth of progeny. In addition, the extra phosphoric effects of using high phytase supplementation to overcome the anti-nutritional effects of phytate were studied. The aim of this study was to determine the influence of dietary phytase in breeder hens on yolk nutrients, hatchability, chick quality, and growth rate of their progeny, and their subsequent performance to 42 d post-hatch when fed diets with the same phytase concentrations. Breeder hens (n = 216) were divided into 3 groups receiving nutrient-adequate diets with reduced calcium (Ca) and phosphorus (P) (by 0.16% and 0.15%, respectively), supplemented with either 500, 1500, or 4500 FTU/kg phytase from 27 to 50 weeks of age. Eggs were collected at 38 weeks of age and incubated. On the day of hatch, the chick quality and hatchability were determined, and 18 chicks/group were euthanized for yolk sac collection and the determination of inositol and glycerol concentrations. The remaining chicks were divided into three groups, receiving different diets with reduced Ca and P (by 0.16% and 0.15%, respectively), supplemented with 0, 500, or 1500 FTU/kg phytase to 42 d post-hatch. Increasing the phytase concentration in the breeder hen diet linearly (p < 0.05) increased the number of early embryo deaths and decreased the number of late deaths and pips. The inositol concentration in the yolk sac at day of hatch increased (quadratic; p < 0.05) as the phytase dose increased in the breeder hen diet. The breeder hen diet (p < 0.05) influenced the body weight (BW), feed intake (FI), and feed conversion ratio (FCR) up to 21 days of age. The supplementation of breeder hen diets with 1500 FTU/kg phytase increased the concentration of sodium (Na), magnesium (Mg), potassium (K), manganese (Mn), and zinc (Zn) in the yolk sac. The inclusion of phytase doses up to 4500 FTU/kg appeared to influence embryo mortality, chick feed intake, and BW gain to 21 days and the FCR throughout the entire production phase. [ABSTRACT FROM AUTHOR]

With the spread of the Industry 4.0 concept, implementing Artificial Intelligence approaches on the shop floor that allow companies to increase their competitiveness in the market is starting to be prioritized. Due to the complexity of the processes used in the industry, the inclusion of a real-time Quality Prediction methodology avoids a considerable number of costs to companies. This paper exposes the whole process of introducing Artificial Intelligence in plastic injection molding processes in a company in Portugal. All the implementations and methodologies used are presented, from data collection to real-time classification, such as Data Augmentation and Human-in-the-Loop labeling, among others. This approach also allows predicting and alerting with regard to process quality loss. This leads to a reduction in the production of non-compliant parts, which increases productivity and reduces costs and environmental footprint. In order to understand the applicability of this system, it was tested in different injection molding processes (traditional and stretch and blow) and with different materials and products. The results of this document show that, with the approach developed and presented, it was possible to achieve an increase in Overall Equipment Effectiveness (OEE) of up to 12%, a reduction in the process downtime of up to 9% and a significant reduction in the number of non-conforming parts produced. This improvement in key performance indicators proves the potential of this solution. [ABSTRACT FROM AUTHOR]

In this work we explore the structure of a G-rich DNA aptamer termed AT11-L2 (TGGTGGTGGTTGTTGTTGGTGGTGGTGGT; derivative of AT11) by evaluating the formation and stability of G-quadruplex (G4) conformation under different experimental conditions such as KCl concentration, temperature, and upon binding with a variety of G4 ligands (360A, BRACO-19, PDS, PhenDC3, TMPyP4). We also determined whether nucleolin (NCL) can be a target of AT11-L2 G4. Firstly, we assessed by circular dichroism, UV and NMR spectroscopies the formation of G4 by AT11-L2. We observed that, for KCl concentrations of 65 mM or less, AT11-L2 adopts hybrid or multiple topologies. In contrast, a parallel topology predominates for buffer containing 100 mM of KCl. The Tm of AT11-L2 in 100 mM of KCl is 38.9 °C, proving the weak stability of this sequence. We also found that upon titration with two molar equivalents of 360A, BRACO-19 and PhenDC3, the G4 is strongly stabilized and its topology is maintained, while the addition of 3.5 molar equivalents of TMPyP4 promotes the disruption of G4. The KD values between AT11-L2 G4, ligands and NCL were obtained by fluorescence titrations and are in the range of µM for ligand complexes and nM when adding NCL. In silico studies suggest that four ligands bind to the AT11-L2 G4 structure by stacking interactions, while the RBD1,2 domains of NCL interact preferentially with the thymines of AT11-L2 G4. Finally, AT11-L2 G4 co-localized with NCL in NCL-positive tongue squamous cell carcinoma cell line. [ABSTRACT FROM AUTHOR]

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to ≅108 CAR T cells/kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here, we tested CD8α/4-1BB compared to CD28-based anti-CAIX CAR peripheral blood mononuclear cells (PBMCs) releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo. Using a ≅107 CAR PBMCs cells/kg dose, anti-CAIX CD28 CAR T cells releasing anti-PD-L1 IgG highly decrease both tumor volume and weight in vivo, avoiding the occurrence of metastasis. This antitumoral superiority of CD28-based CAR PBMCs cells compared to 4-1BB occurred under ICB via PD-L1. Furthermore, the T cell exhaustion status in peripheral CD4 T cells, additionally to CD8, was critical for CAR T cells efficiency. The lack of hepatotoxicity and nephrotoxicity upon the administration of a 107 CAR PMBCs cells/kg dose is the basis for carrying out clinical trials using anti-CAIX CD28 CAR PBMCs cells releasing anti-PD-L1 antibodies or anti-CAIX 4-1BB CAR T cells, offering exciting new prospects for the treatment of refractory ccRCC and hypoxic tumors. [ABSTRACT FROM AUTHOR]

Annexin A1 (AnxA1) is a pleiotropic protein that exerts essential roles in breast cancer (BC) growth and aggressiveness. In our previous work, we described the autocrine signaling of AnxA1 through formyl peptide receptor 1 (FPR1) in the triple-negative (TN) BC cell line, MDA-MB-231. Here, we aimed to describe the interaction between the AnxA1/FPR1 and the Interleukin-6 (IL-6) signaling pathways and their role in the tumor microenvironment (TME). First, we demonstrated that AnxA1 and IL-6 expression levels are correlated in BC tissue samples. In three TNBC cell lines, overexpression of both AnxA1 and IL-6 was also identified. Next, we inhibited FPR1, the IL-6 receptor and STAT3 in both MDA-MB-231 and MDA-MB-157 cells. The FPR1 inhibition led to increased levels of IL-6 and secreted AnxA1 in both cell lines. On the other side, inhibition of the IL-6 receptor or STAT3 led to the impairment of AnxA1 secretion, suggesting the essential role of the IL-6 signaling cascade in the activation of the AnxA1/FPR1 autocrine axis. Finally, we described the interaction between IL-6 and the AnxA1/FPR1 pathways and their role on the TME by analyzing the effect of supernatants derived from MDA-MB-231 and MDA-MB-157 cells under the inhibition of FPR1 or IL-6 signaling on fibroblast cell motility. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of forced swimming on the technetium-99m (99mTc) labeling of blood constituents (BloCs). Rats (Wistar) were submitted to forced swim. In previous experiments, swimming animals would recover for different periods of time. Animals not submitted to swimming were used as control. Blood samples were obtained and the 99mTc labeling of BloCs was carried out. Blood cells (BCs), plasma (P), insoluble fractions (IF-P and IF-BCs), and soluble fractions (SF-P and SF-BC) were isolated. Radioactivity was determined, and the percentage of 99mTc incorporated (%ATI) was calculated in each fraction. Results showed that forced swimming decreased the percentage of 99mTc incorporated (%ATI) in IF-P (p < 0.05). It is suggested that the 99mTc labeling of BloCs could be used to verify the effects of the stress conditions on BloCs and that the radionuclide fixation on plasma proteins might be altered in rats submitted to acute stress induced by forced swimming, returning to control levels after recovery. [ABSTRACT FROM AUTHOR]

In addition to its nutritional value, Paullinia cupana (guarana) is commonly used in traditional medicine, known for its stimulant and medicinal properties. This investigation evaluated the effects of a guarana extract in combination with whole-body vibration (WBV) exercises on Wistar rats. Rats (male, n = 20) were divided into the following four groups: control (CON), treated with guarana (GUA), submitted to 50 Hz of WBV (WBV-E), treated with guarana and submitted to 50 Hz of WBV (GUA + WBV-E), daily for 6-weeks. Guarana altered (p < 0.05) the uptake of the radiopharmaceutical sodium pertechnetate (Na99mTcO4) in muscle. Additionally, it modified the stool consistency, and in combination with WBV decreased the food intake without modifying body mass. The levels of calcium increased in the groups submitted to WBV exercises (WBV-E and GUA + WBV-E) as compared with the GUA group. The outcomes provide additional evidence of the biological effects of guarana separately or in combination with WBV and supports the use of guarana as a functional food. [ABSTRACT FROM AUTHOR]

Featured Application: The concomitant treatment proposed by this study could be an important therapeutic tool used to improve the complications arising from type 1 diabetes mellitus and could provide a clinical alternative for those individuals that currently only have the pharmacological path. The treatment of type 1 diabetes mellitus (T1DM) is a health challenge and new approaches to solve this issue have been proposed. This study evaluated the biological effects of a concomitant treatment with Coriandrum sativum (coriander) and whole-body vibration (WBV) exercise on rats with T1DM. It is hypothesized that this concomitant treatment will improve the metabolic state of rats with T1DM. T1DM was induced with alloxan. Male rats (n = 20) were divided into four groups: control (CON), treated with coriander (COR), exposed to 50 Hz of WBV (WBV), and treated with coriander and exposed to 50 Hz of WBV (COR + WBV), weekly for 28 days. No alterations were observed in the metabolic outcome variables relating to the organs, specific biomarkers, body mass, food intake, and stool consistency. Alloxan-induced T1DM resisted desirable therapeutic effects of the proposed concomitant treatment as it inhibited antidiabetic activity of the coriander. Putting together all findings, neither coriander nor WBV exercise were capable of improving the metabolic state of the Wistar rats with T1DM. This data set and the knowledge in the literature about the effects of the concomitant treatment in healthy animals can provide greater reliability concerning the effects of coriander. [ABSTRACT FROM AUTHOR]

This article discusses how computational intelligence techniques are applied to fuse spectral images into a higher level image of land cover distribution for remote sensing, specifically for satellite image classification. We compare a fuzzy-inference method with two other computational intelligence methods, decision trees and neural networks, using a case study of land cover classification from satellite images. Further, an unsupervised approach based on k-means clustering has been also taken into consideration for comparison. The fuzzy-inference method includes training the classifier with a fuzzy-fusion technique and then performing land cover classification using reinforcement aggregation operators. To assess the robustness of the four methods, a comparative study including three years of land cover maps for the district of Mandimba, Niassa province, Mozambique, was undertaken. Our results show that the fuzzy-fusion method performs similarly to decision trees, achieving reliable classifications; neural networks suffer from overfitting; while k-means clustering constitutes a promising technique to identify land cover types from unknown areas. [ABSTRACT FROM AUTHOR]

Short sea shipping is an important research topic and is of practical interest for the shipping and transport industries in many regions across the globe. However, it is important to consider that short sea shipping cannot operate in standalone mode as it requires other modes of transportation to cover the first and last mile. The benefits of this form of transportation have been significantly discussed in the literature, but there is still the need to involve the relevant stakeholders in this discussion, listening to their specific concerns when dealing with transport decisions and taking the opportunity to disseminate the advantages of short sea shipping, often combined with other transport modes, as has been carried out in paper [[2]] in this Special Issue. [Extracted from the article]

Heat shock proteins (HSPs) are abundant cellular proteins involved with protein homeostasis. They have both constitutive and inducible isoforms, whose expression levels are further increased by stress conditions, such as temperature elevation, reduced oxygen levels, infection, inflammation and exposure to toxic substances. In these situations, HSPs exert a pivotal role in offering protection, preventing cell death and promoting cell recovery. Although the majority of HSPs functions are exerted in the cytoplasm and organelles, several lines of evidence reveal that HSPs are able to induce cell responses in the extracellular milieu. HSPs do not possess secretion signal peptides, and their secretion was subject to widespread skepticism until the demonstration of the role of unconventional secretion forms such as exosomes. Secretion of HSPs may confer immune system modulation and be a cell-to-cell mediated form of increasing stress resistance. Thus, there is a wide potential for secreted HSPs in resistance of cancer therapy and in the development new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is an eye disease typically associated with the aging and can be classified into two types—namely, the exudative and the nonexudative AMD. Currently available treatments for exudative AMD use intravitreal injections, which are associated with high risk of infection that can lead to endophthalmitis, while no successful treatments yet exist for the nonexudative form of AMD. In addition to the pharmacologic therapies administered by intravitreal injection already approved by the Food and Drug Administration (FDA) in exudative AMD, there are some laser treatments approved that can be used in combination with the pharmacological therapies. In this review, we discuss the latest developments of treatment options for AMD. Relevant literature available from 1993 was used, which included original articles and reviews available in PubMed database and also information collected from Clinical Trials Gov website using "age-related macular degeneration" and "antiangiogenic therapies" as keywords. The clinical trials search was limited to ongoing trials from 2015 to date. [ABSTRACT FROM AUTHOR]

This paper studies the possibilities of closer integration of short sea shipping, with other components of the Trans-European Transport Networks, shifting a significant share of road freight onto rail corridors and inland waterways. A numerical model of transport networks is used to support the calculation of the main parameters driving transport decisions, for multiple pairs of origin/destination representing statistical regions of the European Union, and for different, alternative intermodal and unimodal transport chains. Results are presented using a geographic information system. This approach is applied in a case study dedicated to the evaluation of the competitiveness of transport chains based on short sea shipping between Portugal and The Netherlands, integrated with other components of Trans-European Transport Networks (rail freight corridors and inland waterways), compared to road haulage-based transport chains. Conclusions are drawn regarding the geographical scope of the relative competitiveness of these transport chains and policy investment insights are presented. [ABSTRACT FROM AUTHOR]

This paper proposes a new model for short-term forecasting of electric energy production in a photovoltaic (PV) plant. The model is called HIstorical SImilar MIning (HISIMI) model; its final structure is optimized by using a genetic algorithm, based on data mining techniques applied to historical cases composed by past forecasted values of weather variables, obtained from numerical tools for weather prediction, and by past production of electric power in a PV plant. The HISIMI model is able to supply spot values of power forecasts, and also the uncertainty, or probabilities, associated with those spot values, providing new useful information to users with respect to traditional forecasting models for PV plants. Such probabilities enable analysis and evaluation of risk associated with those spot forecasts, for example, in offers of energy sale for electricity markets. The results of spot forecasting of an illustrative example obtained with the HISIMI model for a real-life grid-connected PV plant, which shows high intra-hour variability of its actual power output, with forecasting horizons covering the following day, have improved those obtained with other two power spot forecasting models, which are a persistence model and an artificial neural network model. [ABSTRACT FROM AUTHOR]

The eye is a very complex organ comprising several physiological and physical barriers that compromise drug absorption into deeper layers. Nanoemulsions are promising delivery systems to be used in ocular drug delivery due to their innumerous advantages, such as high retention time onto the site of application and the modified release profile of loaded drugs, thereby contributing to increasing the bioavailability of drugs for the treatment of eye diseases, in particular those affecting the posterior segment. In this review, we address the main factors that govern the development of a suitable nanoemulsion formulation for eye administration to increase the patient's compliance to the treatment. Appropriate lipid composition and type of surfactants (with a special emphasis on cationic compounds) are discussed, together with manufacturing techniques and characterization methods that are instrumental for the development of appropriate ophthalmic nanoemulsions. [ABSTRACT FROM AUTHOR]

The fast spread of SARS-CoV-2 has led to a global pandemic, calling for fast and accurate assays to allow infection diagnosis and prevention of transmission. We aimed to develop a molecular beacon (MB)-based detection assay for SARS-CoV-2, designed to detect the ORF1ab and S genes, proposing a two-stage COVID-19 testing strategy. The novelty of this work lies in the design and optimization of two MBs for detection of SARS-CoV-2, namely, concentration, fluorescence plateaus of hybridization, reaction temperature and real-time results. We also identify putative G-quadruplex (G4) regions in the genome of SARS-CoV-2. A total of 458 nasopharyngeal and throat swab samples (426 positive and 32 negative) were tested with the MB assay and the fluorescence levels compared with the cycle threshold (Ct) values obtained from a commercial RT-PCR test in terms of test duration, sensitivity, and specificity. Our results show that the samples with higher fluorescence levels correspond to those with low Ct values, suggesting a correlation between viral load and increased MB fluorescence. The proposed assay represents a fast (total duration of 2 h 20 min including amplification and fluorescence reading stages) and simple way of detecting SARS-CoV-2 in clinical samples from the upper respiratory tract. [ABSTRACT FROM AUTHOR]

The non-coding RNAs (ncRNA) are RNA transcripts with different sizes, structures and biological functions that do not encode functional proteins. RNA G-quadruplexes (rG4s) have been found in small and long ncRNAs. The existence of an equilibrium between rG4 and stem−loop structures in ncRNAs and its effect on biological processes remains unexplored. For example, deviation from the stem−loop leads to deregulated mature miRNA levels, demonstrating that miRNA biogenesis can be modulated by ions or small molecules. In light of this, we report several examples of rG4s in certain types of ncRNAs, and the implications of G4 stabilization using small molecules, also known as G4 ligands, in the regulation of gene expression, miRNA biogenesis, and miRNA−mRNA interactions. Until now, different G4 ligands scaffolds were synthesized for these targets. The regulatory role of the above-mentioned rG4s in ncRNAs can be used as novel therapeutic approaches for adjusting miRNA levels. [ABSTRACT FROM AUTHOR]

Quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and of quinuclidine surfactants were used to develop oil-in-water nanoemulsions with the purpose of selecting the best long-term stable nanoemulsion for the ocular administration of triamcinolone acetonide (TA). The combination of the best physicochemical properties (i.e., mean droplet size, polydispersity index, zeta potential, osmolality, viscoelastic properties, surface tension) was considered, together with the cell viability assays in ARPE-19 and HMC3 cell lines. Surfactants with cationic properties have been used to tailor the nanoemulsions' surface for site-specific delivery of drugs to the ocular structure for the delivery of TA. They are tailored for the eye because they have cationic properties that interact with the anionic surface of the eye. [ABSTRACT FROM AUTHOR]

Oil-in-water nanoemulsions (NEs) are considered a suitable nanotechnological approach to improve the eye-related bioavailability of lipophilic drugs. The potential of cationic NEs is prominent due to the electrostatic interaction that occurs between the positively charged droplets with the negatively charged mucins present in the tear film. This interaction offers prolonged NEs residence at the ocular surface, increasing the drug absorption. Triamcinolone acetonide (TA) is one of the first pharmacologic strategies applied as an intravitreal injection in the treatment of age-related macular degeneration (AMD). Newly synthesized quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and quinuclidine surfactants have been screened with the purpose to select the best compound to formulate long-term stable NEs that combine the best physicochemical properties for the loading of TA intended for ocular administration. [ABSTRACT FROM AUTHOR]

This paper applies a methodology for computing external costs in an intermodal transport network that includes short sea shipping to explore the impact of external costs in its competitiveness. The network, which includes roads, freight railways, maritime and inland waterway connections, considers the specific characteristics of different transport alternatives and vehicle types, providing a fair comparison of the various modes. A case study focused on freight transportation between Northern Portugal and 75 destinations (NUTS2 regions) in north-western Europe is presented. The potential of different intermodal routes that include short sea shipping is assessed, including not only internal costs and times but also external costs per mode and unit of cargo. The impact of the different cost approaches in each country of transit is shown along with the progress that has been made in the integration of external costs, using the most recent EU estimates on marginal costs coverage ratios per country for freight transport modes. The results support the modal shift from road to sea in this corridor, providing means for modal comparison and for the development of short sea shipping's image as a sustainable mode of transportation. [ABSTRACT FROM AUTHOR]

The cellular immune response plays an important role in COVID-19, caused by SARS-CoV-2. This feature makes use of in vitro models' useful tools to evaluate vaccines and biopharmaceutical effects. Here, we developed a two-step model to evaluate the cellular immune response after SARS-CoV-2 infection-induced or spike protein stimulation in peripheral blood mononuclear cells (PBMC) from both unexposed and COVID-19 (primo-infected) individuals (Step1). Moreover, the supernatants of these cultures were used to evaluate its effects on lung cell lines (A549) (Step2). When PBMC from the unexposed were infected by SARS-CoV-2, cytotoxic natural killer and nonclassical monocytes expressing inflammatory cytokines genes were raised. The supernatant of these cells can induce apoptosis of A549 cells (mock vs. Step2 [mean]: 6.4% × 17.7%). Meanwhile, PBMCs from primo-infected presented their memory CD4+ T cells activated with a high production of IFNG and antiviral genes. Supernatant from past COVID-19 subjects contributed to reduce apoptosis (mock vs. Step2 [ratio]: 7.2 × 1.4) and to elevate the antiviral activity (iNOS) of A549 cells (mock vs. Step2 [mean]: 31.5% × 55.7%). Our findings showed features of immune primary cells and lung cell lines response after SARS-CoV-2 or spike protein stimulation that can be used as an in vitro model to study the immunity effects after SARS-CoV-2 antigen exposure. [ABSTRACT FROM AUTHOR]

Progress in the design of G-quadruplex (G4) binding ligands relies on the availability of approaches that assess the binding mode and nature of the interactions between G4 forming sequences and their putative ligands. The experimental approaches used to characterize G4/ligand interactions can be categorized into structure-based methods (circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography), affinity and apparent affinity-based methods (surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and mass spectrometry (MS)), and high-throughput methods (fluorescence resonance energy transfer (FRET)-melting, G4-fluorescent intercalator displacement assay (G4-FID), affinity chromatography and microarrays. Each method has unique advantages and drawbacks, which makes it essential to select the ideal strategies for the biological question being addressed. The structural- and affinity and apparent affinity-based methods are in several cases complex and/or time-consuming and can be combined with fast and cheap high-throughput approaches to improve the design and development of new potential G4 ligands. In recent years, the joint use of these techniques permitted the discovery of a huge number of G4 ligands investigated for diagnostic and therapeutic purposes. Overall, this review article highlights in detail the most commonly used approaches to characterize the G4/ligand interactions, as well as the applications and types of information that can be obtained from the use of each technique. [ABSTRACT FROM AUTHOR]

Electromagnetic forces can lead to the structural failure of power transformers due to extreme loading conditions, vibration, and/or fatigue. Therefore, studying the nature and the magnitude of these forces is a key task in the design and failure analysis of such important equipment. Keeping this issue in mind, this work aims at conducting a numerical analysis in order to evaluate the mechanical stresses and displacements of windings in power transformers due to the action of electromagnetic forces. With this purpose, a finite element model is developed considering electromagnetic and mechanical effects assuming short-circuit conditions. The study compares the cases employing copper and aluminum windings with header tap, in different temperatures. The model developed in this work is verified against analytical solutions. The numerical calculations allow for performing a detailed analysis in terms of the distribution of both displacements and stresses along the windings, which is of great relevance for identifying critical structural points and avoiding structural failure. Overall, the obtained results demonstrate that the finite element model is a useful tool for the structural design of power transformers that allow for investigating and optimizing key aspects before manufacturing. [ABSTRACT FROM AUTHOR]

This paper discusses the most attractive emission compliance options (emission abatement technologies and cleaner fuels) in intermodal transport chains that include short sea shipping. Most studies on emissions-based transport chain comparisons have estimated high levels of nitrogen and sulfur oxide emissions in maritime transportation, decreasing its competitiveness. However, the consequences of regulatory and technological developments and the integration of maritime transport in intermodal transport chains have not yet been considered in detail. In order to address this research gap, a numerical model for computing emissions from different transport modes in an intermodal transport network, under the effect of these developments, is presented that is based on bottom–up emission factors that depend on the fuel type, engine type, and operational profile of each vehicle. Different emissions scenarios are chosen for specific unimodal and intermodal routes (short sea shipping-based) between Portugal and northwestern Europe. Conclusions are drawn on estimated values of air pollutant emissions and greenhouse emissions, in CO2-eq per unit of cargo, in each scenario. These results allow the identification of the most environmentally friendly transport chains, thus supporting the development of adequate transport policies. [ABSTRACT FROM AUTHOR]

We have designed AS1411-N6, a derivative of the nucleolin (NCL)-binding aptamer AS1411, by adding six nucleotides to the 5′-end that are complementary to nucleotides at the 3′-end forcing it into a stem-loop structure. We evaluated by several biophysical techniques if AS1411-N6 can adopt one or more conformations, one of which allows NCL binding. We found a decrease of polymorphism of G-quadruplex (G4)-forming sequences comparing to AS1411 and the G4 formation in presence of K+ promotes the duplex folding. We also studied the binding properties of ligands TMPyP4, PhenDC3, PDS, 360A, and BRACO-19 in terms of stability, binding, topology maintenance of AS1411-N6, and NCL recognition. The melting experiments revealed promising stabilizer effects of PhenDC3, 360A, and TMPyP4, and the affinity calculations showed that 360A is the most prominent affinity ligand for AS1411-N6 and AS1411. The affinity determined between AS1411-N6 and NCL denoting a strong interaction and complex formation was assessed by PAGE in which the electrophoretic profile of AS1411-N6 showed bands of the dimeric form in the presence of the ligands and NCL. [ABSTRACT FROM AUTHOR]

Simple Summary: Desmoplastic small round cell tumor is a rare neoplasm with extremely aggressive behavior. Despite the multimodal treatment for newly diagnosed patients with chemotherapy, cytoreductive surgery and radiation, the cure rate is still low. For relapsed or progressive disease, there is limited data regarding second and third-line therapies. Novel agents have shown only modest activity. Recent molecular changes have been identified in this disease and this opens opportunities to be explored in future clinical trials. Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1–WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials. [ABSTRACT FROM AUTHOR]

The biological activity of Rhinella icterica parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5β,12β)-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide, marinobufagin, bufogenin B, 11α,19-dihydroxy-telocinobufagin, bufotalin, monohydroxylbufotalin, 19-oxo-cinobufagin, 3α,12β,25,26-tetrahydroxy-7-oxo-5β-cholestane-26-O-sulfate, and cinobufagin-3-hemisuberate that were identified as alkaloid and steroid compounds, in addition to marinoic acid and N-methyl-5-hydroxy-tryptamine. In chick brain slices, all fractions caused a slight decrease in cell viability, as also seen with the highest concentration of RIPS tested. In chick biventer cervicis neuromuscular preparations, RIPS and all four fractions significantly inhibited junctional acetylcholinesterase (AChE) activity. In this preparation, only fraction RI23 completely mimicked the pharmacological profile of RIPS, which included a transient facilitation in the amplitude of muscle twitches followed by progressive and complete neuromuscular blockade. Mass spectrometric analysis showed that RI23 consisted predominantly of bufogenins, a class of steroidal compounds known for their cardiotonic activity mediated by a digoxin- or ouabain-like action and the blockade of voltage-dependent L-type calcium channels. These findings indicate that the pharmacological activities of RI23 (and RIPS) are probably mediated by: (1) inhibition of AChE activity that increases the junctional content of Ach; (2) inhibition of neuronal Na+/K+-ATPase, leading to facilitation followed by neuromuscular blockade; and (3) blockade of voltage-dependent Ca2+ channels, leading to stabilization of the motor endplate membrane. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship among genetic, transcriptional and functional findings. Classically, gene expression has been evaluated by steady-state mRNA, however, this does not take translational control into consideration, which contributes considerably to the composition of the proteome. In this study, we evaluated the transcriptomic and translatomic signature of a GBM obtained from a single patient focusing in tumor heterogeneity. In a sampling of eight fragments, we investigated the translation rates, mTORC1 and ERK1/2 pathways and identified both total and polysome associated mRNAs. An increased translation rate was observed in fragments with high-grade histological features. High-grade histology was also associated with the expression of genes related to extracellular matrix (ECM) and angiogenesis, in both transcriptomes and translatomes. However, genes associated with epithelial to mesenchymal transition and stress response, were observed only in translatomes from high-grade fragments. Overall, our results demonstrate that isolation of translated mRNA can be used to identify biomarkers and reveal previously unrecognized determinants of heterogeneity in GBMs. [ABSTRACT FROM AUTHOR]

The use of hydrogen as an alternative to fossil fuels for vehicle propulsion is already a reality. However, due to its physical characteristics, storage is still a challenge. There is an innovative way, presented in this study, to store hydrogen in conventional vehicles propelled by spark-ignition reciprocating engines and fuel cells, using hydrogen as fuel; the storage of hydrogen will be at high pressure within small spheres randomly packed in a tank, like the conventional tank of fuel used nowadays in current vehicles. Therefore, the main purpose of the present study is to assess the performance of this storage system and compare it to others already applied by car manufacturers in their cars. In order to evaluate the performance of this storage system, some parameters were taken into account: The energy stored by volume and stored by weight, hydrogen leakage, and compliance with current standards. This system is safer than conventional storage systems since hydrogen is stored inside small spheres containing small amounts of hydrogen. Besides, its gravimetric energy density (GED) is threefold and the volumetric energy density (VED) is about half when compared with homologous values for conventional systems, and both exceed the targets set by the U.S. Department of Energy. Regarding the leakage of hydrogen, it complies with the European Standards, provided a suitable choice of materials and dimensions is made. [ABSTRACT FROM AUTHOR]

The effective monitoring and maintenance of power lines are becoming increasingly important due to a global growing dependence on electricity. The costs and risks associated with the traditional foot patrol and helicopter-based inspections can be reduced by using UAVs with the appropriate sensors. However, this implies developing algorithms to make the power line inspection process reliable and autonomous. In order to overcome the limitations of visual methods in the presence of poor light and noisy backgrounds, we propose to address the problem of power line detection and modeling based on LiDAR. The PL 2 DM, Power Line LiDAR-based Detection and Modeling, is a novel approach to detect power lines. Its basis is a scan-by-scan adaptive neighbor minimalist comparison for all the points in a point cloud. The power line final model is obtained by matching and grouping several line segments, using their collinearity properties. Horizontally, the power lines are modeled as a straight line, and vertically as a catenary curve. Using a real dataset, the algorithm showed promising results both in terms of outputs and processing time, adding real-time object-based perception capabilities for other layers of processing. [ABSTRACT FROM AUTHOR]

Rare sarcomas present significant treatment challenges compared to more prevalent soft tissue sarcomas due to limited treatment options and a poor understanding of their biology. This study investigates a unique case of penile sarcoma, providing a comprehensive morphological and molecular analysis. Through the creation of experimental patient-derived models-including patient-derived xenograft (PDX), 3D, and monolayer primary cultures-we successfully replicated crucial molecular traits observed in the patient's tumor, such as smooth muscle actin and CD99 expression, along with specific mutations in genes like TSC2 and FGFR4 . These models are helpful in assessing the potential for an in-depth exploration of this tumor's biology. This comprehensive approach holds promise in identifying potential therapeutic avenues for managing this exceedingly rare soft tissue sarcoma.

Heat shock proteins (HSPs) are abundant cellular proteins involved with protein homeostasis. They have both constitutive and inducible isoforms, whose expression levels are further increased by stress conditions, such as temperature elevation, reduced oxygen levels, infection, inflammation and exposure to toxic substances. In these situations, HSPs exert a pivotal role in offering protection, preventing cell death and promoting cell recovery. Although the majority of HSPs functions are exerted in the cytoplasm and organelles, several lines of evidence reveal that HSPs are able to induce cell responses in the extracellular milieu. HSPs do not possess secretion signal peptides, and their secretion was subject to widespread skepticism until the demonstration of the role of unconventional secretion forms such as exosomes. Secretion of HSPs may confer immune system modulation and be a cell-to-cell mediated form of increasing stress resistance. Thus, there is a wide potential for secreted HSPs in resistance of cancer therapy and in the development new therapeutic strategies.