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This document provides insights into lipid-based nanosystems and their potential therapeutic applications. Lipid-based nanosystems, such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), liposomes, and others, have been extensively studied for their ability to improve drug transport and efficacy through various routes of administration. The document highlights 16 research articles published in a special issue on lipid-based nanosystems, covering topics such as breast cancer treatment, anti-tumor efficacy, antidepressant activity, and ocular drug delivery. The most investigated diseases include cancer, brain diseases, ocular diseases, skin diseases, microbial infections, and metabolic diseases. The authors express their gratitude to the contributors and reviewers of the special issue for their valuable contributions. [Extracted from the article]

Schistosoma mansoni eggs retained in host tissues induce innate cytokine release, contributing to the induction of Type-2 immune responses and granuloma formation, important to restrain cytotoxic antigens, but leading to fibrosis. Interleukin(IL)-33 participates in experimental models of inflammation and chemically induced fibrosis, but its role in S. mansoni-induced fibrosis is still unknown. To explore the role of the IL-33/suppressor of the tumorigenicity 2 (ST2) pathway, serum and liver cytokine levels, liver histopathology, and collagen deposition were comparatively evaluated in S. mansoni-infected wild-type (WT) and IL-33-receptor knockout (ST2−/−) BALB/c mice. Our data show similar egg counts and hydroxyproline in the livers of infected WT and ST2−/− mice; however, the extracellular matrix in ST2−/− granulomas was loose and disorganised. Pro-fibrotic cytokines, such as IL-13 and IL-17, and the tissue-repairing IL-22 were significantly lower in ST2−/− mice, especially in chronic schistosomiasis. ST2−/− mice also showed decreased α-smooth muscle actin (α-SMA) expression in granuloma cells, in addition to reduced Col III and Col VI mRNA levels and reticular fibres. Therefore, IL-33/ST2 signalling is essential for tissue repairing and myofibroblast activation during S. mansoni infection. Its disruption results in inappropriate granuloma organisation, partly due to the reduced type III and VI collagen and reticular fibre formation. [ABSTRACT FROM AUTHOR]

The use of agroforestry residues for energy purposes has long been a reality in Brazil. About 84.8% of the produced electricity comes from renewable resources; vegetable biomass contributes 9.1% to this total. This percentage has the potential to increase if Amazon biomass residues are processed to be used as fuel. The major difficulty for this scenario is the lack of available information on energy properties, mainly the HHVs for Amazon agroforestry biomass types. Considering that there are important deviations in the equations for predicting the HHVs of Amazon biomass types in the literature, the main objective of this work was to propose equations to determine the HHVs of these biomass types using the proximate or ultimate analysis results as input. The methodology adopted to develop such equations was simple and multiple linear regression methods, using experimental results for HHVs and proximate and ultimate analyses for biomass types from the north region of Brazil. Four distinct equations were considered based on ranges from the proximate and ultimate analyses of the biomass types to deliver better results. The obtained equations were validated by application to 28 other biomass types from the same region. The proposed HHV equations presented good agreement between predicted and experimental values, with errors below 5% for equations based on proximate analysis and below 3% for equations based on ultimate analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the clinical benefit of new anticancer therapies, such as immune checkpoint inhibitors, lung cancer remains the most frequent cause of cancer-related death worldwide, thus supporting the need to develop novel anticancer treatments. Endothelial cells of the tumor-associated vasculature are easily accessible to drugs administered intravenously, besides having greater genetic stability than neoplastic cells and thus lowering the risk of developing drug resistance. In this respect, the identification of alternative targets, and therapeutic strategies, within the tumor vasculature is of high relevance. Accordingly, this work aimed at characterizing nucleolin expression in patient-derived pulmonary carcinomas and further validating nucleolin as a novel target to mediate successful therapeutic interventions against human lung cancers. The highlighted prognostic value of nucleolin points towards the applicability of nucleolin-based targeting strategies against nucleolinhigh pulmonary carcinomas, present in every disease stage, in a clinical trial setting. Notwithstanding the advances in the treatment of lung cancer with immune checkpoint inhibitors, the high percentage of non-responders supports the development of novel anticancer treatments. Herein, the expression of the onco-target nucleolin in patient-derived pulmonary carcinomas was characterized, along with the assessment of its potential as a therapeutic target. The clinical prognostic value of nucleolin for human pulmonary carcinomas was evaluated through data mining from the Cancer Genome Atlas project and immunohistochemical detection in human samples. Cell surface expression of nucleolin was evaluated by flow cytometry and subcellular fraction Western blotting in lung cancer cell lines. Nucleolin mRNA overexpression correlated with poor overall survival of lung adenocarcinoma cancer patients and further predicted the disease progression of both lung adenocarcinoma and squamous carcinoma. Furthermore, a third of the cases presented extra-nuclear expression, contrasting with the nucleolar pattern in non-malignant tissues. A two- to twelve-fold improvement in cytotoxicity, subsequent to internalization into the lung cancer cell lines of doxorubicin-loaded liposomes functionalized by the nucleolin-binding F3 peptide, was correlated with the nucleolin cell surface levels and the corresponding extent of cell binding. Overall, the results suggested nucleolin overexpression as a poor prognosis predictor and thus a target for therapeutic intervention in lung cancer. [ABSTRACT FROM AUTHOR]

Explainable Machine Learning comprises methods and techniques that enable users to better understand the machine learning functioning and results. This work proposes an ontology that represents explainable machine learning experiments, allowing data scientists and developers to have a holistic view, a better understanding of the explainable machine learning process, and to build trust. We developed the ontology by reusing an existing domain-specific ontology (ML-SCHEMA) and grounding it in the Unified Foundational Ontology (UFO), aiming at achieving interoperability. The proposed ontology is structured in three modules: (1) the general module, (2) the specific module, and (3) the explanation module. The ontology was evaluated using a case study in the scenario of the COVID-19 pandemic using healthcare data from patients, which are sensitive data. In the case study, we trained a Support Vector Machine to predict mortality of patients infected with COVID-19 and applied existing explanation methods to generate explanations from the trained model. Based on the case study, we populated the ontology and queried it to ensure that it fulfills its intended purpose and to demonstrate its suitability. [ABSTRACT FROM AUTHOR]

There is an increasing demand for robotic manipulators to perform more complex and versatile tasks. In order to fulfill this need, expeditious calibration and estimation techniques are required as a first step for the correct usage of the manipulator. This article aims at finding a subset of these algorithms that could be used in a generic manipulator and should allow for its prompt use. Two models for the representation of the pose of the manipulator are described and used in the state estimation problem. The results of the implementation are tested, and some performance metrics are obtained. [ABSTRACT FROM AUTHOR]

We present in this work a first assessment of the imaging and topographic mapping capabilities of the InSAeS4 system, which is a single-pass interferometric airborne X-Band Synthetic Aperture Radar (SAR). In particular, we first provide a brief description of the InSAeS4 sensor. Then, we discuss the results of our analysis on the SAR and interferometric SAR products relevant to the first flight-test campaign. More specifically, we have exploited as reference the GPS measurements relevant to nine Corner Reflectors (CRs) deployed over the illuminated area during the campaign and a laser scanner Digital Elevation Model (DEM). From the analysis carried out on the CRs we achieved a mean geometric resolution, for the SAR products, of about 0.14 m in azimuth and 0.49 m in range, a positioning misalignment with standard deviation of 0.07 m in range and 0.08 m in azimuth, and a height error with standard deviation of 0.51 m. From the comparison with the laser scanner DEM we estimated a height error with standard deviation of 1.57 m. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative protection, in the fate of NSC under aging and depression-like contexts. We showed that chronic treatment with tert-butyl hydroperoxide induces NSC aging, markedly reducing SIRT3 protein. SIRT3 overexpression, in turn, restored mitochondrial oxidative stress and the differentiation potential of aged NSCs. Notably, SIRT3 was also shown to physically interact with the long chain acyl-CoA dehydrogenase (LCAD) in NSCs and to require its activation to prevent age-impaired neurogenesis. Finally, the SIRT3 regulatory network was investigated in vivo using the unpredictable chronic mild stress (uCMS) paradigm to mimic depressive-like behavior in mice. Interestingly, uCMS mice presented lower levels of neurogenesis and LCAD expression in the same neurogenic niches, being significantly rescued by physical exercise, a well-known upregulator of SIRT3 and lipid metabolism. Our results suggest that targeting NSC metabolism, namely through SIRT3, might be a suitable promising strategy to delay NSC aging and confer stress resilience. [ABSTRACT FROM AUTHOR]

The nasal route has been used for many years for the local treatment of nasal diseases. More recently, this route has been gaining momentum, due to the possibility of targeting the central nervous system (CNS) from the nasal cavity, avoiding the blood−brain barrier (BBB). In this area, the use of lipid nanoparticles, such as nanostructured lipid carriers (NLC) and solid lipid nanoparticles (SLN), in nasal formulations has shown promising outcomes on a wide array of indications such as brain diseases, including epilepsy, multiple sclerosis, Alzheimer's disease, Parkinson's disease and gliomas. Herein, the state of the art of the most recent literature available on in vitro studies with nasal formulations of lipid nanoparticles is discussed. Specific in vitro cell culture models are needed to assess the cytotoxicity of nasal formulations and to explore the underlying mechanism(s) of drug transport and absorption across the nasal mucosa. In addition, different studies with 3D nasal casts are reported, showing their ability to predict the drug deposition in the nasal cavity and evaluating the factors that interfere in this process, such as nasal cavity area, type of administration device and angle of application, inspiratory flow, presence of mucoadhesive agents, among others. Notwithstanding, they do not preclude the use of confirmatory in vivo studies, a significant impact on the 3R (replacement, reduction and refinement) principle within the scope of animal experiments is expected. The use of 3D nasal casts to test nasal formulations of lipid nanoparticles is still totally unexplored, to the authors best knowledge, thus constituting a wide open field of research. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted nanomedicine-based approaches that aim at the simultaneous delivery of synergistic drug combinations to multiple cellular populations are of high relevance for tackling heterogeneity on solid tumors. Considering that cancer stem cells (CSC) may originate from non-stem cancer cells, single-drug regimens targeting only one of these cell populations could enable tumors to evade treatments. As such, the identification of a common marker, such as nucleolin, might result in a therapeutic advantage. The results herein generated suggested a transversal role of nucleolin in the internalization of F3 peptide-targeted pegylated pH-sensitive liposomes into bulk ovarian cancer cells, including putative CSC-enriched ovarian cells. The intracellular delivery of a drug combination such as the one tested herein was relevant in the context of cell lines with higher intrinsic resistances to doxorubicin. The enhanced efficacy of the F3 peptide-targeted liposomal combination of doxorubicin/C6-ceramide was supported by the downregulation of the Akt pathway, within a specific range of basal level of expression. Targeting multiple cellular populations is of high therapeutic relevance for the tackling of solid tumors heterogeneity. Herein, the ability of pegylated and pH-sensitive liposomes, functionalized with the nucleolin-binding F3 peptide and containing doxorubicin (DXR)/C6-ceramide synergistic combination, to target, in vitro, ovarian cancer, including ovarian cancer stem cells (CSC), was assessed. The underlying molecular mechanism of action of the nucleolin-mediated intracellular delivery of C6-ceramide to cancer cells was also explored. The assessment of overexpression of surface nucleolin expression by flow cytometry was critical to dissipate differences identified by Western blot in membrane/cytoplasm of SKOV-3, OVCAR-3 and TOV-112D ovarian cancer cell lines. The former was in line with the significant extent of uptake into (bulk) ovarian cancer cells, relative to non-targeted and non-specific counterparts. This pattern of uptake was recapitulated with putative CSC-enriched ovarian SKOV-3 and OVCAR-3 sub-population (EpCAMhigh/CD44high). Co-encapsulation of DXR:C6-ceramide into F3 peptide-targeted liposomes improved cytotoxic activity relative to liposomes containing DXR alone, in an extent that depended on the intrinsic resistance to DXR and on the incubation time. The enhanced cytotoxicity of the targeted combination was mechanistically supported by the downregulation of PI3K/Akt pathway by C6-ceramide, only among the nucleolin-overexpressing cancer cells presenting a basal p-Akt/total Akt ratio lower than 1. [ABSTRACT FROM AUTHOR]

Cancer, one of the most mortal diseases worldwide, is characterized by the gain of specific features and cellular heterogeneity. Clonal evolution is an established theory to explain heterogeneity, but the discovery of cancer stem cells expanded the concept to include the hierarchical growth and plasticity of cancer cells. The activation of epithelial-to-mesenchymal transition and its molecular players are widely correlated with the presence of cancer stem cells in tumors. Moreover, the acquisition of certain oncological features may be partially attributed to alterations in the levels, location or function of nucleolin, a multifunctional protein involved in several cellular processes. This review aims at integrating the established hallmarks of cancer with the plasticity of cancer cells as an emerging hallmark; responsible for tumor heterogeneity; therapy resistance and relapse. The discussion will contextualize the involvement of nucleolin in the establishment of cancer hallmarks and its application as a marker protein for targeted anticancer therapies [ABSTRACT FROM AUTHOR]

The kNN machine learning method is widely used as a classifier in Human Activity Recognition (HAR) systems. Although the kNN algorithm works similarly both online and in offline mode, the use of all training instances is much more critical online than offline due to time and memory restrictions in the online mode. Some methods propose decreasing the high computational costs of kNN by focusing, e.g., on approximate kNN solutions such as the ones relying on Locality-Sensitive Hashing (LSH). However, embedded kNN implementations also need to address the target device's memory constraints, especially as the use of online classification needs to cope with those constraints to be practical. This paper discusses online approaches to reduce the number of training instances stored in the kNN search space. To address practical implementations of HAR systems using kNN, this paper presents simple, energy/computationally efficient, and real-time feasible schemes to maintain at runtime a maximum number of training instances stored by kNN. The proposed schemes include policies for substituting the training instances, maintaining the search space to a maximum size. Experiments in the context of HAR datasets show the efficiency of our best schemes. [ABSTRACT FROM AUTHOR]

The increasingly aging society in developed countries has raised attention to the role of technology in seniors' lives, namely concerning isolation-related issues. Independent seniors that live alone frequently neglect meals, hydration and proper medication-taking behavior. This work aims at eating and drinking recognition in free-living conditions for triggering smart reminders to autonomously living seniors, keeping system design considerations, namely usability and senior-acceptance criteria, in the loop. To that end, we conceived a new dataset featuring accelerometer and gyroscope wrist data to conduct the experiments. We assessed the performance of a single multi-class classification model when compared against several binary classification models, one for each activity of interest (eating vs. non-eating; drinking vs. non-drinking). Binary classification models performed consistently better for all tested classifiers (k-NN, Naive Bayes, Decision Tree, Multilayer Perceptron, Random Forests, HMM). This evidence supported the proposal of a semi-hierarchical activity recognition algorithm that enabled the implementation of two distinct data stream segmentation techniques, the customization of the classification models of each activity of interest and the establishment of a set of restrictions to apply on top of the classification output, based on daily evidence. An F1-score of 97% was finally attained for the simultaneous recognition of eating and drinking in an all-day acquisition from one young user, and 93% in a test set with 31 h of data from 5 different unseen users, 2 of which were seniors. These results were deemed very promising towards solving the problem of food and fluids intake monitoring with practical systems which shall maximize user-acceptance. [ABSTRACT FROM AUTHOR]

With the increase of life expectancy, neurodegenerative disorders are becoming not only a health but also a social burden worldwide. However, due to the multitude of pathophysiological disease states, current treatments fail to meet the desired outcomes. Therefore, there is a need for new therapeutic strategies focusing on more integrated, personalized and effective approaches. The prospect of using neural stem cells (NSC) as regenerative therapies is very promising, however several issues still need to be addressed. In particular, the potential actions of pharmacological agents used to modulate NSC activity are highly relevant. With the ongoing discussion of cannabinoid usage for medical purposes and reports drawing attention to the effects of cannabinoids on NSC regulation, there is an enormous, and yet, uncovered potential for cannabinoids as treatment options for several neurological disorders, specifically when combined with stem cell therapy. In this manuscript, we review in detail how cannabinoids act as potent regulators of NSC biology and their potential to modulate several neurogenic features in the context of pathophysiology. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative protection, in the fate of NSC under aging and depression-like contexts. We showed that chronic treatment with tert-butyl hydroperoxide induces NSC aging, markedly reducing SIRT3 protein. SIRT3 overexpression, in turn, restored mitochondrial oxidative stress and the differentiation potential of aged NSCs. Notably, SIRT3 was also shown to physically interact with the long chain acyl-CoA dehydrogenase (LCAD) in NSCs and to require its activation to prevent age-impaired neurogenesis. Finally, the SIRT3 regulatory network was investigated in vivo using the unpredictable chronic mild stress (uCMS) paradigm to mimic depressive-like behavior in mice. Interestingly, uCMS mice presented lower levels of neurogenesis and LCAD expression in the same neurogenic niches, being significantly rescued by physical exercise, a well-known upregulator of SIRT3 and lipid metabolism. Our results suggest that targeting NSC metabolism, namely through SIRT3, might be a suitable promising strategy to delay NSC aging and confer stress resilience.