Mucus represents the first line of defense of our respiratory tract and mucociliary clearance is essential for maintaining the homeostasis of airway epithelium. The latter mechanisms are altered in asthma and mucus plugging of proximal and distal airways is the main cause of death in cases of fatal asthma. Starting from the influential review performed by Luke R. Bonser and David J. Erle in 2017, we discuss the latest evidence in terms of mucins regulation and potential treatment of mucus hypersecretion and tissue remodeling in severe asthma. Full article

Glaesserella parasuis is a habitual bacterium of pigs’ upper respiratory tracts. Its infection initiates with the invasion and colonization of the lower respiratory tracts of pigs, and develops as the bacteria survive host pulmonary defenses and clearance by alveolar macrophages. Alveolar macrophage-derived nitric oxide (NO) is recognized as an important mediator that exerts antimicrobial activity as well as immunomodulatory effects. In this study, we investigated the effects and the signaling pathway of NO generation in porcine alveolar macrophages 3D4/21 during G. parasuis infection. We demonstrated a time and dose-dependent generation of NO in 3D4/21 cells by G. parasuis, and showed that NO production required bacterial viability and nitric oxide synthase 2 upregulation, which was largely contributed by G. parasuis-induced nuclear factor-κB signaling’s activation. Moreover, the porcine alveolar macrophage-derived NO exhibited prominent bacteriostatic effects against G. parasuis and positive host immunomodulation effects by inducing the production of cytokines and chemokines during infection. G. parasuis in turn, selectively upregulated several nitrate reductase genes to better survive this NO stress, revealing a battle of wits during the bacteria–host interactions. To our knowledge, this is the first direct demonstration of NO production and its anti-infection effects in alveolar macrophages with G. parasuis infection. Full article

Numerous studies over the years have shown that oxidative stress plays a major role in the development of the disease. Oxidative stress involvement in COPD opens up the possibility of using antioxidant therapies in the treatment of the disease. However, so far, these therapies have shown no clinical benefit indicating that more basic research efforts are needed to understand the underlying mechanisms by which oxidative stress leads to the development of COPD. Full article

Leptin is a hormone crucial in the regulation of food intake and body-weight maintenance. However, the genes and gene variants that influence its plasma levels are still not well known. Results of studies investigating polymorphisms in candidate genes have been inconsistent, and, in addition, very few genome-wide association studies (GWAS) have been undertaken. Our aim was to investigate the genes and gene variants most associated with plasma leptin concentrations in a high-cardiovascular-risk Mediterranean population. We measured plasma leptin in 1011 men and women, and analyzed the genetic factors associated using three approaches: (1) Analyzing the single nucleotide polymorphisms (SNPs) reported in a GWAS meta-analysis in other populations (including an SNP in/near each of these LEP, SLC32A1, GCKR, CCNL, COBLL1, and FTO genes); (2) Investigating additional SNPs in/near those genes, also including the RLEP gene; and (3) Undertaking a GWAS to discover new genes. We did not find any statistically significant associations between the previously published SNPs and plasma leptin (Ln) in the whole population adjusting for sex and age. However, on undertaking an extensive screening of other gene variants in those genes to capture a more complete set of SNPs, we found more associations. Outstanding among the findings was the heterogeneity per sex. We detected several statistically significant interaction terms with sex for these SNPs in the candidate genes. The gene most associated with plasma leptin levels was the FTO gene in men (specifically the rs1075440 SNP) and the LEPR in women (specifically the rs12145690 SNP). In the GWAS on the whole population, we found several new associations at the p < 1 × 10⁻⁵ level, among them with the rs245908-CHN2 SNP (p = 1.6 × 10⁻⁶). We also detected a SNP*sex interaction at the GWAS significance level (p < 5 × 10⁻⁸), involving the SLIT3 gene, a gene regulated by estrogens. In conclusion, our study shows that the SNPs selected as relevant for plasma leptin levels in other populations, are not good markers for this Mediterranean population, so supporting those studies claiming a bias when generalizing GWAS results to different populations. These population-specific differences may include not only genetic characteristics, but also age, health status, and the influence of other environmental variables. In addition, we have detected several sex-specific effects. These results suggest that genomic analyses, involving leptin, should be estimated by sex and consider population-specificity for more precise estimations. Full article

The actin-binding protein ACTN4 belongs to a family of actin-binding proteins and is a non-muscle alpha-actinin that has long been associated with cancer development. Numerous clinical studies showed that changes in ACTN4 gene expression are correlated with aggressiveness, invasion, and metastasis in certain tumors. Amplification of the 19q chromosomal region where the gene is located has also been reported. Experimental manipulations with ACTN4 expression further confirmed its involvement in cell proliferation, motility, and epithelial-mesenchymal transition (EMT). However, both clinical and experimental data suggest that the effects of ACTN4 up- or down-regulation may vary a lot between different types of tumors. Functional studies demonstrated its engagement in a number of cytoplasmic and nuclear processes, ranging from cytoskeleton reorganization to regulation of different signaling pathways. Such a variety of functions may be the reason behind cell type and cell line specific responses. Herein, we will review research progress and controversies regarding the prognostic and functional significance of ACTN4 for tumorigenesis. Full article

Research Highlights: A large scale effort to screen, characterize, and select Trichoderma strains with the potential to antagonize Armillaria species revealed promising candidates for field applications. Background and Objectives: Armillaria species are among the economically most relevant soilborne tree pathogens causing devastating root diseases worldwide. Biocontrol agents are environment-friendly alternatives to chemicals in restraining the spread of Armillaria in forest soils. Trichoderma species may efficiently employ diverse antagonistic mechanisms against fungal plant pathogens. The aim of this paper is to isolate indigenous Trichoderma strains from healthy and Armillaria-damaged forests, characterize them, screen their biocontrol properties, and test selected strains under field conditions. Materials and Methods: Armillaria and Trichoderma isolates were collected from soil samples of a damaged Hungarian oak and healthy Austrian spruce forests and identified to the species level. In vitro antagonism experiments were performed to determine the potential of the Trichoderma isolates to control Armillaria species. Selected biocontrol candidates were screened for extracellular enzyme production and plant growth-promoting traits. A field experiment was carried out by applying two selected Trichoderma strains on two-year-old European Turkey oak seedlings planted in a forest area heavily overtaken by the rhizomorphs of numerous Armillaria colonies. Results: Although A. cepistipes and A. ostoyae were found in the Austrian spruce forests, A. mellea and A. gallica clones dominated the Hungarian oak stand. A total of 64 Trichoderma isolates belonging to 14 species were recovered. Several Trichoderma strains exhibited in vitro antagonistic abilities towards Armillaria species and produced siderophores and indole-3-acetic acid. Oak seedlings treated with T. virens and T. atrobrunneum displayed better survival under harsh soil conditions than the untreated controls. Conclusions: Selected native Trichoderma strains, associated with Armillaria rhizomorphs, which may also have plant growth promoting properties, are potential antagonists of Armillaria spp., and such abilities can be exploited in the biological control of Armillaria root rot. Full article

Background: [⁶⁸Ga]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [⁶⁸Ga]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infections in pigs. Methods: Eight pigs with osteomyelitis and soft tissue infections in the right hind limb were dynamically PET scanned for 60 min along with arterial blood sampling. The fraction of radioactivity in the blood accounted for by the parent tracer was evaluated with radio-high-performance liquid chromatography. One- and two-tissue compartment models were used for pharmacokinetic evaluation. Post-mortem soft tissue samples from one pig were analysed with anti-VAP-1 immunofluorescence. In each analysis, the animal’s non-infected left hind limb was used as a control. Results: Tracer uptake was elevated in soft tissue infections but remained low in osteomyelitis. The kinetics of [⁶⁸Ga]Ga-DOTA-Siglec-9 followed a reversible 2-tissue compartment model. The tracer metabolized quickly; however, taking this into account, produced more ambiguous results. Infected soft tissue samples showed endothelial cell surface expression of the Siglec-9 receptor VAP-1. Conclusion: The kinetics of [⁶⁸Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model. Full article

In this work, we investigate numerically a one-dimensional wave equation in generalized form. The system considers the presence of constant damping and functional anomalous diffusion of the Riesz type. Reaction terms are also considered, in such way that the mathematical model can be presented in variational form when damping is not present. As opposed to previous efforts available in the literature, the reaction terms are not only functions of the solution. Instead, we consider the presence of smooth functions that depend on fractional derivatives of the solution function. Using a finite-difference approach, we propose a numerical scheme to approximate the solutions of the fractional wave equation. Along with this integrator, we propose discrete forms of the local and the total energy operators. In a first stage, we show rigorously that the energy properties of the continuous system are mimicked by our discrete methodology. In particular, we prove that the discrete system is dissipative (respectively, conservative) when damping is present (respectively, absent), in agreement with the continuous model. The theoretical numerical analysis of this system is more complicated in light of the presence of the functional form of the anomalous diffusion. To solve this problem, some novel technical lemmas are proved and used to establish the stability and the quadratic convergence of the scheme. Finally, we provide some computer simulations to show the capability of the scheme to conserve/dissipate the energy. Various fractional problems with functional forms of the anomalous diffusion of the solution are considered to that effect. Full article

Background: Ideas of reference (IRs) are observed in the general population on the continuum of the psychotic phenotype (as a type of psychotic-like experiences, PLE). The instruments usually used to evaluate IRs show some problems: They depend on the cooperation of the participant, comprehension of items, social desirability, etc. Aims: The Testal emotional counting Stroop (TECS) was developed for the purpose of improving evaluation of individuals vulnerable to psychosis and its relationship with ideas of reference. The TECS (two versions) was applied as an implicit evaluation instrument for IRs and related processes for early identification of persons vulnerable to psychosis and to test the possible influence of emotional symptomatology. Method: A total of 160 participants (67.5% women) from the general population were selected (Mean (M) = 24.12 years, standard deviation (SD) = 5.28), 48 vulnerable and 112 non-vulnerable. Results: Vulnerability to psychosis was related to greater latency in response to referential stimuli. Version 4 of the TECS showed a slight advantage in identifying more latency in response to referential stimuli among participants with vulnerability to psychosis (Cohen’s d = 1.08). Emotional symptomatology (especially stress), and IQ (premorbid) mediated the relationship between vulnerability and IR response latency. Conclusions: The application of the implicit Testal emotional counting Stroop test (TECS) is useful for evaluating processes related to vulnerability to psychosis, as demonstrated by the increased latency of response to referential stimuli. Full article

Excavation of clay soil is one of the most important economic branches in the northern part of Croatia. The impact of clay soil in Croatia compared to the global exploitation fields of clay soil is negligible. Modern methods of clay excavation during winter months due to negligible amounts are not profitable. Therefore, it is important to optimize clay soil excavation throughout the year to increase the efficiency of exploitation and increase profits. In the case of large amounts of precipitation (rain), clay absorbs water and becomes grain. For this reason, access to the exploitation field and excavation itself becomes impossible. Air temperature also plays an important role in excavation. Long-lasting low air temperatures below 0 °C during the winter months result in clay frost. As a result, excavation cannot occur at that time. The paper describes a new method of modeling the precipitation and air temperature on the exploitation fields of clay in Northwest Croatia on the exploitation fields of Cukavec and Cukavec II. The method involves the calculation of the drought index and use of the rescaled adjusted partial sums (RAPS) statistical method and its application on a time series of total daily precipitation and average daily temperatures as a climatic indicator of any observed area. Using this process, it is possible to determine the time period of the year when clay soil can be excavated. Full article

The current paper investigates the influence of the hardware setup and parameters of a 3D printing process on the resulting sample strength obtained through fused filament fabrication (FFF) technology. Three-point bending was chosen as the strength measure for samples printed with the long side oriented along the Z-axis. A single CAD model was converted into NC-programs through the same slicing software to be run on five different desktop FFF 3D printers with filament of the same brand and color. For all the printers, the same ranges of layer thickness values from 0.1 to 0.3 mm and feed rates from 25 to 75 mm/s were planned to be varied. The first four machines considered in the study were off the shelf devices available on the market, and the fifth was a quick prototype of a desktop machine design based on the analysis of pros and cons of the four machines considered. The results of the study show that the hardware setup of a desktop 3D printer can drastically change the influence of basic technological parameters such as feed rate and layer thickness on the interlayer bonding. This means that many of the conclusions drawn from previous studies connecting the technological parameters of the FFF process with the mechanical performance of parts and samples may only be correct for specific hardware setups. Full article

This study proposes a method for determining the optimal image date to improve the evaluation of cultivated land quality (CLQ). Five vegetation indices: leaf area index (LAI), difference vegetation index (DVI), enhanced vegetation index (EVI), normalized difference vegetation index (NDVI), and ratio vegetation index (RVI) are first retrieved using the PROSAIL model and Gaofen-1 (GF-1) images. The indices are then introduced into four regression models at different growth stages for assessing CLQ. The optimal image date of CLQ evaluation is finally determined according to the root mean square error (RMSE). This method is tested and validated in a rice growth area of Southern China based on 115 sample plots and five GF-1 images acquired at the tillering, jointing, booting, heading to flowering, and milk ripe and maturity stage of rice in 2015, respectively. The results show that the RMSEs between the measured and estimated CLQ from four vegetation index-based regression models at the heading to flowering stage are smaller than those at the other growth stages, indicating that the image date corresponding with the heading to flowering stage is optimal for CLQ evaluation. Compared with other vegetation index-based models, the LAI-based logarithm model provides the most accurate estimates of CLQ. The optimal model is also driven using the GF-1 image at the heading to flowering stage to map CLQ of the study area, leading to a relative RMSE of 14.09% at the regional scale. This further implies that the heading to flowering stage is the optimal image time for evaluating CLQ. This study is the first effort to provide an applicable method of selecting the optimal image date to improve the estimation of CLQ and thus advanced the literature in this field. Full article

The research on the environmental impacts of corn-derived products has been mainly on cultivation techniques and the production of biofuels, so there is limited information on the impacts produced by the transformation of corn for human consumption. The tortilla is a millennial product derived from corn of which consumption is increasing in North America. The aim of this study is to identify the environmental hotspots of the tortilla using a life cycle assessment (LCA) approach. The process studied included only the corn–nixtamalisation–dough–tortillas production. The functional unit is one kg of tortillas packed in kraft paper. The impacts of the tortilla production process were evaluated using SimaPro 8.5.0 software, considering ReCiPe Midpoint. The production has the greatest impact in 15 of the 18 impact categories. The normalisation reveals that the most significant impacts concentrate in the categories terrestrial acidification (TA), particulate matter formation (PMF), marine ecotoxicity (MET) and fossil fuel depletion (FD). Improvements in the cultivation could mean more environmentally friendly tortilla production. Full article