Proteins contain many sites that are subject to modification by electrophiles. Detection and characterisation of these modifications can give insights into environmental agents and endogenous processes that may be contributing factors to chronic human diseases. An untargeted approach, utilising mass spectrometry to detect modified amino acids or peptides, has been applied to blood proteins haemoglobin and albumin, focusing in particular on the N-terminal valine residue of haemoglobin and the cysteine-34 residue in albumin. Technical developments to firstly detect simultaneously multiple adducts at these sites and then subsequently to identify them are reviewed here. Recent studies in which the methods have been applied to biomonitoring human exposure to environmental toxicants are described. With advances in sensitivity, high-throughput handling of samples and robust quality control, these methods have considerable potential for identifying causes of human chronic disease and of identifying individuals at risk. Full article

Flaxseed is a rich source of the omega-3 fatty acid, alpha linolenic acid, the lignan secoisolariciresinol diglucoside and fiber. These compounds provide bioactivity of value to the health of animals and humans through their anti-inflammatory action, anti-oxidative capacity and lipid modulating properties. The characteristics of ingesting flaxseed or its bioactive components are discussed in this article. The benefits of administering flaxseed or the individual bioactive components on health and disease are also discussed in this review. Specifically, the current evidence on the benefits or limitations of dietary flaxseed in a variety of cardiovascular diseases, cancer, gastro-intestinal health and brain development and function, as well as hormonal status in menopausal women, are comprehensive topics for discussion. Full article

In cognitive electronic warfare, when a typical combat vehicle, such as an unmanned combat air vehicle (UCAV), uses radar sensors to explore an unknown space, the target-searching fails due to an inefficient servoing/tracking system. Thus, to solve this problem, we developed an autonomous reasoning search method that can generate efficient decision-making actions and guide the UCAV as early as possible to the target area. For high-dimensional continuous action space, the UCAV’s maneuvering strategies are subject to certain physical constraints. We first record the path histories of the UCAV as a sample set of supervised experiments and then construct a grid cell network using long short-term memory (LSTM) to generate a new displacement prediction to replace the target location estimation. Finally, we enable a variety of continuous-control-based deep reinforcement learning algorithms to output optimal/sub-optimal decision-making actions. All these tasks are performed in a three-dimensional target-searching simulator, i.e., the Explorer game. Please note that we use the behavior angle (BHA) for the first time as the main factor of the reward-shaping of the deep reinforcement learning framework and successfully make the trained UCAV achieve a 99.96% target destruction rate, i.e., the game win rate, in a 0.1 s operating cycle. Full article

The electro-Fenton system has the ability to degrade wastewater and has received attention from many researchers. Currently, the core development objective is to effectively increase the degraded wastewater decolorization efficiency in the system. In this study, to improve the electro-Fenton system reaction rate and overall electrical properties, we used polyvinylidene difluoride to fix carbon nanotubes (CNTs) and graphene onto the system cathode (carbon felt electrode), which was then used to process Reactive Black 5 wastewater. Furthermore, we (1) used scanning electron microscopy to observe the structural changes in the electrode surface after modification; (2) used the Tafel curve to determine the electrode corrosion voltage and corrosion rate; and (3) analyzed the azo-dye decolorization level. The results showed that the maximum system decolorization rates of the CNT- and graphene-modified carbon felt electrodes were 55.3% and 70.1%, respectively. These rates were, respectively, 1.2 and 1.5 times higher than that of the unmodified carbon felt electrode, implying that we successfully improved the cathode characteristics. The modified electrode exhibited an improved conductivity and corrosion resistance, which, in turn, improved the system decolorization efficiency. This significantly increased the electro-Fenton system overall efficacy, making it valuable for future applications. Full article

Gliomas are malignant brain tumors characterized by rapid spread and growth into neighboring tissues and graded I–IV by the World Health Organization. Glioblastoma is the fastest growing and most devastating IV glioma. The aim of this paper is to evaluate the biological effects of two potent and selective Monoamine Oxidase B (MAO-B) inhibitors, Cmp3 and Cmp5, in C6 glioma cells and in CTX/TNA2 astrocytes in terms of cell proliferation, apoptosis occurrence, inflammatory events and cell migration. These compounds decrease C6 glioma cells viability sparing normal astrocytes. Cell cycle analysis, the Mitochondrial Membrane Potential (MMP) and Reactive Oxygen Species (ROS) production were detected, revealing that Cmp3 and Cmp5 induce a G1 or G2/M cell cycle arrest, as well as a MMP depolarization and an overproduction of ROS; moreover, they inhibit the expression level of inducible nitric oxide synthase 2, thus contributing to fatal drug-induced oxidative stress. Cmp5 notably reduces glioma cell migration via down-regulating Matrix Metalloproteinases 2 and 9. This study demonstrated that our novel MAO-B inhibitors increase the oxidative stress level resulting in a cell cycle arrest and markedly reduces glioma cells migration thus reinforcing the hypothesis of a critical role-played by MAO-B in mediating oncogenesis in high-grade gliomas. Full article

In the last few years, substantial progress has been made in the treatment of ovarian cancer, with increased knowledge about the biology of the disease. Ovarian cancer is a neoplasm strongly linked to defects in DNA repair mechanisms, where deficiency in the homologous recombination (HR) system results in a better response of ovarian cancers to therapy, whether platinum-based chemotherapy, anthracyclines, or poly (ADP-ribose) polymerase (PARP) inhibitors. More recently, it has been demonstrated that different ovarian cancer histotypes may have different immunogenicity. Interestingly, defects in HR systems are associated more frequently with higher tumor infiltrating lymphocytes, providing a rationale for developing combination therapy with immune-modulating agents and PARP inhibitors. Again, locoregional therapies combining heat shock and chemotherapy delivery have been shown to induce an anticancer immune response in vitro. Thus, the potential for locoregional therapeutic approaches that may impact the immune system, perhaps in combination with immune-modulating agents or PARP inhibitors, needs to be further explored. With this premise, we reviewed the main biological and clinical data demonstrating a strict interplay between the immune system, DNA repair mechanisms, and intraperitoneal therapies in ovarian cancer, with a focus on potential future therapeutic implications. Full article

In recent years, there has been an increasing interest and need for alternatives to structural fumigations, and one alternative that has been used across the industry is aerosol insecticides. Previous tests inside a pilot-scale mill demonstrated that aerosol particle size, delivery method, and the spatial configuration of the mill all influenced effectiveness. However, there is no research conducted inside large commercial facilities. The objective of this research was to evaluate a pyrethrin-plus-methoprene aerosol application inside a commercial mill on adult Tribolium confusum Jacquelin duVal, confused flour beetle, directly exposed to the aerosol and residual effects on larvae. Additionally, five aerodynamic particle sizer spectrometers were placed in the facility and recorded instantaneous spray concentration and estimated aerosol deposition. Adult T. confusum exposed nearest to the aerosol application points had the highest percentage of affected adults (>60%). The aerosol also had vertical movement when released at the top of a three-story open room; instantaneous concentrations were recorded on the ground floor. The aerosol residual was highly effective after 6-weeks post aerosol exposure, as 80% of the bioassays did not have any adult emergence from exposed larvae. This research demonstrates a practical use of aerosol insecticides and their potential to be an effective alternative to structural fumigations. Full article

Electroanalytical techniques are useful for detection and identification because the instrumentation is simple and can support a wide variety of assays. One example is cyclic square wave voltammetry (CSWV), a practical detection technique for different classes of compounds including explosives, herbicides/pesticides, industrial compounds, and heavy metals. A key barrier to the widespread application of CSWV for chemical identification is the necessity of a high performance, generalizable classification algorithm. Here, machine and deep learning models were developed for classifying samples based on voltammograms alone. The highest performing models were Long Short-Term Memory (LSTM) and Fully Convolutional Networks (FCNs), depending on the dataset against which performance was assessed. When compared to other algorithms, previously used for classification of CSWV and other similar data, our LSTM and FCN-based neural networks achieve higher sensitivity and specificity with the area under the curve values from receiver operating characteristic (ROC) analyses greater than 0.99 for several datasets. Class activation maps were paired with CSWV scans to assist in understanding the decision-making process of the networks, and their ability to utilize this information was examined. The best-performing models were then successfully applied to new or holdout experimental data. An automated method for processing CSWV data, training machine learning models, and evaluating their prediction performance is described, and the tools generated provide support for the identification of compounds using CSWV from samples in the field. Full article

Lung carcinogenesis is a multistep process involving genetic mutations and epigenetic changes, with the acquisition of a malignant phenotype characterized by apoptosis resistance, unregulated proliferation and differentiation, invasion, and metastatic abilities. However, neoplastic development and progression seem to be aided by non-neoplastic cells; the molecules they produced can either promote the immune response or, alternatively, support tumor pathogenesis. Consequently, the relative contribution of tumor-associated inflammatory pathways to cancer development has become crucial information. Interleukin-33 (IL-33) is an IL-1-like alarmin, and it is a ligand for the suppressor of tumorigenicity 2 (ST2) receptor. IL-33 functions as a dual role cytokine with the ability to induce T-helper-type 2 (Th2) immune cells and translocate into the nucleus, suppressing gene transcription. Although its function in immunity- and immune-related disorders is well known, its role in tumorigenesis is still debated. The IL-33/ST2 axis is emerging as a powerful modulator of the tumor microenvironment (TME) by recruiting immune cells, able to modify the TME, supporting malignant proliferation or improving antitumor immunity. In the present review, we discuss IL-33′s potential role in lung carcinogenesis and its possible application as a therapeutic target. Full article

Species interactions are fundamental ecological forces that can have significant impacts on the evolutionary trajectories of species. Nonetheless, the contribution of predator-prey interactions to genetic and phenotypic divergence remains largely unknown. Predatory marine snails of the family Conidae exhibit specializations for different prey items and intraspecific variation in prey utilization patterns at geographic scales. Because cone snails utilize venom to capture prey and venom peptides are direct gene products, it is feasible to examine the evolution of genes associated with changes in resource utilization. Here, we compared feeding ecologies and venom duct transcriptomes of individuals from three populations of Conus miliaris, a species that exhibits geographic variation in prey utilization and dietary breadth, in order to determine the extent to which dietary differences are correlated with differences in venom composition, and if expanded niche breadth is associated with increased variation in venom composition. While populations showed little to no overlap in resource utilization, taxonomic richness of prey was greatest at Easter Island. Changes in dietary breadth were associated with differences in expression patterns and increased genetic differentiation of toxin-related genes. The Easter Island population also exhibited greater diversity of toxin-related transcripts, but did not show increased variance in expression of these transcripts. These results imply that differences in dietary breadth contribute more to the structural and regulatory differentiation of venoms than differences in diet. Full article

Hereditary gingival fibromatosis is a disorder for which the etiology remains unknown. We aimed to evaluate the fibroblasts and histological alterations to give new clues. A father and a daughter of a family showing gingival hereditary fibromatosis were treated, and gingival biopsies were obtained. A histological study revealed dense fibrous tissue, basal lamina disruption, and epithelial cell migration into the connective tissue. Fibroblasts were cultured from the father and daughter and compared with those from a healthy control patient. The results of the biochemical analysis showed increased collagen synthesis, reduced antioxidant CoQ₁₀ content, and high levels of lipid peroxidation. Additionally, fibroblasts culture incubation with the oxidant H₂O₂ increased collagen levels that have been reduced by the addition of the antioxidant CoQ₁₀. We conclude that some fibroblasts metabolic alterations play a significant role in initiating and maintaining persistent fibrotic tissue. Oxidative stress influences the fibroblasts collagen production and could play a particular role in the pathogenesis of hereditary gingival fibromatosis. Full article