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Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline–trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline–trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs. Full article

African swine fever (ASF) is a deadly disease of swine currently causing a worldwide pandemic, leading to severe economic consequences for the porcine industry. The control of disease spread is hampered by the limitation of available effective vaccines. Live attenuated vaccines (LAVs) are currently the most advanced vaccine prototypes, providing strong protection against ASF. However, the significant advances achieved using LAVs must be complemented with further studies to analyze vaccine-induced immunity. Here, we characterized the onset of cross-protective immunity triggered by the LAV candidate BA71ΔCD2. Intranasally vaccinated pigs were challenged with the virulent Georgia 2007/1 strain at days 3, 7 and 12 postvaccination. Only the animals vaccinated 12 days before the challenge had effectively controlled infection progression, showing low virus loads, minor clinical signs and a lack of the unbalanced inflammatory response characteristic of severe disease. Contrarily, the animals vaccinated 3 or 7 days before the challenge just showed a minor delay in disease progression. An analysis of the humoral response and whole blood transcriptome signatures demonstrated that the control of infection was associated with the presence of virus-specific IgG and a cytotoxic response before the challenge. These results contribute to our understanding of protective immunity induced by LAV-based vaccines, encouraging their use in emergency responses in ASF-affected areas. Full article

Hardness is one of the most crucial mechanical properties, serving as a key indicator of a material’s suitability for specific applications and its resistance to fracturing or deformation under operational conditions. Machine learning techniques have emerged as valuable tools for swiftly and accurately predicting material behavior. In this study, regression methods including decision trees, adaptive boosting, extreme gradient boosting, and random forest were employed to forecast Vickers hardness values based solely on scanned monochromatic images of indentation imprints, eliminating the need for diagonal measurements. The dataset comprised 54 images of D2 steel in various states, including commercial, quenched, tempered, and coated with Titanium Niobium Nitride (TiNbN). Due to the limited number of images, non-deep machine learning techniques were utilized. The Random Forest technique exhibited superior performance, achieving a Root Mean Square Error (RMSE) of 0.95, Mean Absolute Error (MAE) of 0.12, and Coefficient of Determination ($R^2$) ≈ 1, surpassing the other methods considered in this study. These results suggest that employing machine learning algorithms for predicting Vickers hardness from scanned images offers a promising avenue for rapid and accurate material assessment, potentially streamlining quality control processes in industrial settings. Full article

This work studied the influence of the voltage parameters on the friction and superlubricity performances of LiPF₆-based ionic liquids (ILs). The results show that the voltage direction and magnitude greatly affected the friction performances of ILs and that macroscale superlubricity can be achieved with a stimulation of −0.1 V. The surface analysis and experiment results indicate that the voltage magnitude influences the coefficient of friction (COF) by determining the types of substances in the tribochemical film formed on the ball, while the voltage direction influences the COF by affecting the adsorption behavior of Li(PEG)⁺ ions on the ball. At −0.1 V, the cation group Li(PEG)⁺ adsorption film and FeOOH-containing tribochemical film contribute to friction reduction. The formation of Fe_xO_y within the tribochemical film results in an increase in friction at −0.8 V. The limited adsorption of Li(PEG)⁺ ions and the formation of Fe_xO_y contribute to the elevated COF at +0.1 V. This work proves that the friction performances of LiPF₆-based ILs could be affected by voltage parameters. A lubrication model was proposed hoping to provide a basic understanding of the lubrication mechanisms of ILs in the electric environment. Full article

Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines and 3D tumor models. To address this goal, a well-characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G > T (p.(Gly12Val)) was used. Fluorescently labeled tumor cells were injected into the perivitelline space of 2 days’ post-fertilization zebrafish embryos. At 1 day post-injection, xenografts were assessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib and trametinib + luminespib. Subsequently, xenografts were euthanized and analyzed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n = 84) in vivo, with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC. Full article

Coastal areas are fundamental enclaves for economic and recreational development, attracting a large population worldwide. However, these factors have generated significant pressure on the coastal landscape, requiring territorial management strategies to protect and control its degradation. The coastal landscape, composed of abiotic and biotic elements, plays a crucial role in human wellbeing and the conservation of the natural environment. This study focuses on the southeast area of the Ría de Arosa, on the western coast of Galicia, known for its unique geomorphological features such as estuaries. The main objective is to generate high-resolution thematic maps for territorial planning and conservation of the natural and cultural landscape. Using methodologies based on geographic information systems, various factors of the natural environment will be analyzed to obtain objective results, presenting cartography of landscape units, along with quality and fragility landscape maps. In addition, active strategies are proposed such as multiple land uses or the development of geotourism to preserve, exploit, and manage the landscape better. This work contributes to better understanding the vulnerability of the coastal landscape and provides practical tools for its sustainable management in a context of accelerated global change. Full article

This article analyzes local-level normative regulations aimed at directly or indirectly conserving the urban landscape in rural areas. Using a discursive analysis methodology on regulatory documents being enforced in a series of localities assigned to a tourism promotion program, the evidence suggests that promotional activity retroactively influences the phraseology of these municipal regulations. The results obtained point to the existence of perpetuating historicist approaches within the current regulations, which appear to largely derive from the search for success in the tourism market and the resulting benefits to the local economy. Full article

The ability of a diagnosis tool to observe an abnormal state of a system remains a major issue for health monitoring. For that purpose, several diagnosis tools have been proposed in the literature. Most of them are developed for specific system characterization, and the genericity of the approaches is not considered. Indeed, most approaches proposed in the literature are based on an expert offline consideration that makes it hard to apply the strategy to other systems. It is therefore important to develop a diagnostic tool that takes as little as possible expert knowledge to reduce the dependency between the tool and the system. This paper, therefore, focuses on the application of a generic diagnosis tool on an open cathode fuel cell. The goal is to feed the diagnosis algorithm with a voltage measurement and let it proceed to a self-clustering of the signal components. Each cluster’s interpretation remains to be established by the expert point of view that is then involved downstream of the diagnosis tool. Full article

Resveratrol, a polyphenolic compound found primarily in red grapes and pomegranates is known as an antioxidant but can act as a pro-oxidant when copper ions are present. Here, resveratrol is demonstrated to reduce cell growth (as evaluated by MTT assay) and promote apoptosis-like cell death (as measured by Histone/DNA ELISA) in prostate cancer cell lines PC3 and C42B. This effect is effectively inhibited by a copper chelator (neocuproine) and reactive oxygen species (ROS) scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide). These inhibitory effects provide evidence that intracellular copper reacts with resveratrol within cancer cells, resulting in DNA damage via the generation of reactive oxygen species. Additionally, it has been demonstrated that non-tumorigenic epithelial cell lines (MCF-10A) grown in media supplemented with copper are more susceptible to growth inhibition by resveratrol, as confirmed by the observed reduction in cell proliferation. Copper supplementation induces enhanced expression of the copper transporter CTR1 in MCF-10A cells, which is reduced by the addition of resveratrol to the media. The selective cell death of cancer cells generated by copper-mediated and ROS mechanisms may help to explain the anticancer properties of resveratrol. Full article

In recent decades, fuzzy logic and fuzzy multi-criteria decision-making systems have been applied in several fields. This paper aims to determine the optimal wind farm siting solution in a fuzzy environment. Therefore, the main research question of the present paper is whether and to what extent the uncertainty in the researcher’s judgments affects the ranking of wind farm siting solutions. The fuzzy analytical hierarchy method is applied to an existing case study of wind farm siting on the island of Andros, examining the stability of the final priorities of the alternatives under a regime of gradual increases in ambiguity, as well as whether the introduced ambiguity in the model corresponds to any uncertainty the researcher has during the process of scoring the criteria and alternatives. Five assessment criteria (wind potential, ground slope, distance from road network, distance from high-voltage network, and social acceptance of local population) and eight eligible suitable alternatives (A1–A8) for wind farm siting are considered in the computations. The methodology includes the fuzzification of initial decision-maker judgments, the calculation of fuzzy intermediate priorities (weights), the defuzzification of fuzzy intermediate priorities (weights), and the synthesis of intermediate priorities into final priorities of alternatives, according to the procedures of the crisp AHP (CAHP). Under the assumptions of the initial case study, the results show that the final priorities are quite robust when faced with increased ambiguity. In almost all the examined cases, the alternative initially chosen as the best, A1, is dominant, followed by A3. In addition, in all cases, social acceptance favors alternative A1, and wind velocity favors alternative A8. Therefore, fuzzy multi-criteria methods can be applied to determine an optimal wind farm siting solution when criteria with qualitative characteristics are used and the manifestation of preferences involves strong elements of subjectivity. Full article

Artemisinin has an endoperoxide bridge structure, which can be cleaved by ferrous ions to generate various carbonyl radicals in an oxygen-independent manner, highlighting its potential for treating hypoxic tumors. In our study, we fabricated Tween 80 micelles loaded with Fe₃O₄ nanoparticles and artemisinin for cancer therapy. The synthesized Fe₃O₄ nanoparticles and drug-loaded micelles have particle sizes of about 5 nm and 80 nm, respectively, both exhibiting excellent dispersibility and stability. After uptake by MCF-7 cells, drug-loaded micelles release Fe²⁺ and ART into the cytoplasm, effectively inducing the generation of reactive oxygen species (ROS) in hypoxic conditions, thereby enhancing toxicity against cancer cells. In vitro and in vivo studies have demonstrated that ART and Fe₃O₄ nanoparticles are encapsulated in Tween 80 to form micelles, which effectively prevent premature release during circulation in the body. Although free ART and Fe₃O₄ nanoparticles can inhibit tumor growth, TW80-Fe₃O₄-ART micelles demonstrate a more pronounced inhibitory effect, with a tumor suppression rate of up to 85%. A novel strategy based on artemisinin and ferroptosis is thus offered, holding a favorable prospect for hypoxic cancer therapy. Full article

Heparin products are frequently used in the inpatient setting to prevent and treat venous thromboembolism, but they simultaneously put patients at risk of developing heparin-induced thrombocytopenia (HIT). The 4Ts score determines the pretest probability of HIT. Diagnosis is made with a screening antiplatelet factor (PF4) immunoassay and the serotonin-release assay (SRA) as a confirmatory test. Anti-PF4 assays have high sensitivity (98%) but lower specificity (50%) and result in frequent false-positive tests. We present a rare case from our institution of a patient with anti-PF4–Polyanion ELISA-negative, SRA-positive HIT and describe the challenges in making a timely diagnosis in this case. Full article

Coating technology, as a part of surface engineering, has shown remarkable potential in future industrial applications. With the continuous development and improvement of coating technology, coatings have gradually become an indispensable part of industrial manufacturing, possessing various excellent properties and characteristics, such as superhydrophobicity and self-cleaning, enhanced biological antibacterial properties, and improved corrosion resistance. Intelligent coatings are not only rigid barriers between substrates and the environment but also coatings designed to respond to the environment and improve coating life or achieve certain special functions through this response. Biomimetics is a discipline that studies the structure, function, and behavior of living organisms and applies them to engineering design. Combining bionics with intelligent coating materials can not only improve the performance and functionality of intelligent coatings but also create more intelligent coating materials. This paper includes advanced superhydrophobic intelligent coatings, anticorrosion intelligent coatings, biological antibacterial intelligent coatings, and other intelligent coatings with specific functions. We also provide a detailed overview of the preparation methods and technologies of various representative intelligent coatings, as well as their properties and applications, which will offer some valuable references for the development direction of future intelligent coatings. Full article

The recent seismic activity highlights the crucial need to enhance seismic design and safety assessment methods, particularly for irregular structures, in both new and existing constructions. The present study focuses on structural irregularities in elevation for buildings, as the design of structural systems involves multiple variables that often result in irregularities in many buildings. This work aims to perform a comparative assessment of the criteria adopted for the evaluation of the structural irregularities in elevation present in European and international seismic codes. This paper is structured as follows: Firtsly, it discusses structural irregularities and more specifically the most common types of structural damage due to seismic events. Then, it shows the documented experiences of structural damages in seismic events associated with structural irregularities in China, Italy, Spain, Nepal and Mexico. Additionaly, it discusses the requirements of the standards on irregularities and their limitation in that matter. At the end of this section, the different approaches of each code in irregularities in elevation are compared. All assessed seismic codes addresses the structural irregularity issue, attributing the desired characteristics of a seismic-resistant structure. However, there are considerable development differences between norms, demonstrated on ambiguity of few codes on criteria of vertical irregularies. Full article