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ABSTRACT Due to their frequent coexistence in many polymicrobial infections, including in patients with cystic fibrosis or burn/chronic wounds, many studies have investigated the mechanistic details of the interaction between the opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus aureus. P. aeruginosa rapidly outcompetes S. aureus under in vitro cocultivation conditions, which is mediated by several of P. aeruginosa’s virulence factors. Here, we report that polyphosphate (polyP), an efficient stress defense system and virulence factor in P. aeruginosa, plays a role in the pathogen’s ability to inhibit and kill S. aureus in a contact-independent manner. We show that P. aeruginosa cells characterized by low polyP levels are less detrimental to S. aureus growth and survival while the Gram-positive pathogen is significantly more compromised by the presence of P. aeruginosa cells that produce high levels of polyP. The polyP-dependent phenotype of P. aeruginosa-mediated killing of S. aureus could at least in part be direct, as polyP was detected in the spent media and causes significant damage to the S. aureus cell envelope. However, more likely is that polyP’s effects are indirect through modulating the production of one of P. aeruginosa’s virulence factors, pyocyanin. We show that pyocyanin production in P. aeruginosa occurs polyP-dependently and harms S. aureus through membrane damage and potentially the generation of reactive oxygen species, resulting in the increased expression of antioxidant enzymes. In summary, our study adds a new component to the list of biomolecules that the Gram-negative pathogen P. aeruginosa generates to compete with S. aureus for resources.IMPORTANCEHow do interactions between microorganisms shape the course of polymicrobial infections? Previous studies have provided evidence that the two opportunistic pathogens Pseudomonas aeruginosa and Staphylococcus aureus generate molecules that modulate their interaction with potentially significant impact on disease outcomes. Our study identified the biopolymer polyphosphate (polyP) as a new effector molecule that impacts P. aeruginosa’s interaction with S. aureus. We show that P. aeruginosa kills S. aureus in a polyP-dependent manner, which occurs primarily through the polyP-dependent production of the P. aeruginosa virulence factor pyocyanin. Our findings add a new role for polyP to an already extensive list of functions. A more in-depth understanding of how polyP influences interspecies interactions is critical, as targeting polyP synthesis in bacteria such as P. aeruginosa may have a significant impact on other microorganisms and potentially result in dynamic changes in the microbial composition.

Abstract HIV exposed-uninfected (HEU) infants and children are at risk of developmental delays as compared to HIV uninfected unexposed (HUU) populations. The effects of exposure to in utero HIV and ART regimens on the HEU the developing brain are not well understood. In a cohort of 2-week-old newborns, we used diffusion tensor imaging (DTI) tractography and graph theory to examine the influence of HIV and ART exposure in utero on neonate white matter integrity and organisation. The cohort included HEU infants born to mothers who started ART before conception (HEUpre) and after conception (HEUpost), as well as HUU infants from the same community. We investigated HIV exposure and ART duration group differences in DTI metrics (fractional anisotropy (FA) and mean diffusivity (MD)) and graph measures across white matter. We found increased MD in white matter connections involving the thalamus and limbic system in the HEUpre group compared to HUU. We further identified reduced nodal efficiency in the basal ganglia. Within the HEUpost group, we observed reduced FA in cortical-subcortical and cerebellar connections as well as decreased transitivity in the hindbrain area compared to HUU. Overall, our analysis demonstrated distinct alterations in white matter integrity related to the timing of maternal ART initiation that influence regional brain network properties.

This study presents an analysis of the relationship between the servitization process and energy sustainability in the years 2015–2020. The research refers to 164 selected countries, also divided into two regimes: developed and developing. The transformation of the manufacturing process, and as a result, the economy’s structure, towards servitization, is observed in most countries worldwide. The positive influence of the servitization of production by individual manufacturers on sustainability is widely known. In this research, this relationship is considered on a macroeconomic scale, which is one of the novelties of the study. Particularly, sustainability in the energy sector, indicated as an achievement of the 7th goal of Sustainable Development, is discussed. Energy sustainability is evaluated using a synthetic measure by Perkal. This part of the research shows the problem of the low level of energy sustainability in developing countries (particularly in Africa) compared with developed ones. Moreover, spatio-temporal sensitivity models are estimated and verified. The sensitivity parameter in these models shows the impact of the progress in the servitization process on energy sustainability. The models have been enriched with the effects of spatial dependence between countries, taking into account two types of proximity matrices based on (1) the common border criterion and (2) the similarity of the development levels measured by the Human Development Index. Additionally, the differences in sensitivity between developed and developing countries are considered. The results of the study show that in both cases, the economic servitization positively influences energy sustainability, but the strength of the relationship is stronger in the group of developed countries. This can be, for example, the result of the individual characteristics of the given countries, where African countries mainly benefit from agricultural development. Only after reaching a certain level of economic growth will they be able to obtain sustainability faster through economic servitization.

IntroductionSchool-aged children experience crucial developmental changes in white matter (WM) in adolescence. The human immunodeficiency virus (HIV) affects neurodevelopment. Children living with perinatally acquired HIV (CPHIVs) demonstrate hearing and neurocognitive impairments when compared to their uninfected peers (CHUUs), but investigations into the central auditory system (CAS) WM integrity are lacking. The integration of the CAS and other brain areas is facilitated by WM fibers whose integrity may be affected in the presence of HIV, contributing to neurocognitive impairments.MethodsWe used diffusion tensor imaging (DTI) tractography to map the microstructural integrity of WM between CAS regions, including the lateral lemniscus and acoustic radiation, as well as between CAS regions and non-auditory regions of 11-year-old CPHIVs. We further employed a DTI-based graph theoretical framework to investigate the nodal strength and efficiency of the CAS and other brain regions in the structural brain network of the same population. Finally, we investigated associations between WM microstructural integrity outcomes and neurocognitive outcomes related to auditory and language processing. We hypothesized that compared to the CHUU group, the CPHIV group would have lower microstructural in the CAS and related regions.ResultsOur analyses showed higher mean diffusivity (MD), a marker of axonal maturation, in the lateral lemniscus and acoustic radiations, as well as WM between the CAS and non-auditory regions predominantly in frontotemporal areas. Most affected WM connections also showed higher axial and radial diffusivity (AD and RD, respectively). There were no differences in the nodal properties of the CAS regions between groups. The MD of frontotemporal and subcortical WM-connected CAS regions, including the inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and internal capsule showed negative associations with sequential processing in the CPHIV group but not in the CHUU group.DiscussionThe current results point to reduced axonal maturation in WM, marked by higher MD, AD, and RD, within and from the CAS. Furthermore, alterations in WM integrity were associated with sequential processing, a neurocognitive marker of auditory working memory. Our results provide insights into the microstructural integrity of the CAS and related WM in the presence of HIV and link these alterations to auditory working memory.

We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.

Background and purposeDiabetic nephropathy is a common complications related to high morbidity and mortality in type 2 diabetes. We investigated the action of the dual modulator, PTUPB, a soluble epoxide hydrolase and cyclooxygenase-2 inhibitor against diabetic nephropathy.Experimental approachSixteen-week-old type 2 diabetic and proteinuric obese ZSF1 rats were treated with vehicle, PTUPB or enalapril for 8 weeks. Measurements were made of epoxyeicosatrienoic acids, thromboxane B2 (TBX2 ) and prostaglandin E2 (PGE2 ) in the kidney of these and lean ZSF1 rats along with their blood pressure.Key resultObese ZSF1 rats were diabetic with fivefold higher fasting blood glucose levels and markedly higher HbA1c levels compared with lean ZSF1 rats. PTUPB nor enalapril reduced fasting blood glucose or HbA1c but alleviated the development of diabetic nephropathy. In PTUPB-treated obese ZSF1 rats, glomerular nephrin expression was preserved. Enalapril also alleviated diabetic nephropathy. Diabetic renal injury in obese ZSF1 rats was accompanied by renal inflammation with six to sevenfold higher urinary MCP-1 (CCR2) level and renal infiltration of CD-68 positive cells. PTUPB and enalapril significantly reduced urinary MCP-1 levels and renal mRNA expression of cytokines. Both PTUPB and enalapril lowered blood pressure. PTUPB but not enalapril decreased hyperlipidaemia and liver injury in obese ZSF1 rats.Conclusion and implicationsOverall, the dual modulator PTUPB does not treat hyperglycaemia but can effectively alleviate hypertension, diabetic nephropathy, hyperlipidaemia and liver injury in type 2 diabetic rats. Our data further demonstrate that the renal actions of PTUPB are comparable with a current standard diabetic nephropathy treatment.

The study aims to verify the relationship between the unemployment rate and economic growth in European Union (EU) regions. As the most important macroeconomic relationship, the significance of the dependence between the labour market situation and the output growth is widely known and considered. Analysis in this research was conducted using data for 229 EU regions on the NUTS-2 level in the years 2013–2019. In order to verify the relationship between the unemployment rate and the output growth, the spatio-temporal models for pooled time series and cross-sectional data (TSCS) were estimated. The Fitted Trend and Elasticity Method of verifying Okun’s law was used in the analysis, wherein the deterministic trend factor was enriched with the spatial element. Educational attainment as the additional explanatory variable was included in the models. The neighbourhood between regions was quantified based on two criteria: (1) common border criterion – related to the possibility of population migrations, and (2) similarity of the unemployment rate criterion – related to the imitation effect in the issue of introduced rules and regulations on the labour market by regional governments. One of the hypotheses verified in the investigation is the superiority of the economic neighbourhood over the geographical neighbourhood.

The Balkan countries undergoing the transition must advance their economies to be more competitive. The aim of this paper is to analyse economic growth with a primary focus on the analysis of economic convergence in the Balkan region in the period of 1997–2020. The research analyses the following Balkan economies: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Montenegro, North Macedonia, Romania, Serbia, and Slovenia. This study applies Gross Domestic Product (GDP) as a measure of economic growth and is based on the neoclassical economic growth model: the Solow's convergence concept. The results show that the Balkan countries experienced economic convergence with a speed of 1.82% in the cross-sectional model and 7.87% in the panel data model. It means that the initially less developed economies noted higher economic growth than those richer.

In a landmark decision, the Hague Court of Appeal ordered the Dutch government on 12 February 2024 to stop supplying Israel with F-35 fighter jet parts because there was a “clear risk” that serious violations of international humanitarian law (IHL) would be committed with the aircraft in Gaza. In their unanimous decision, the three judges relied on the European Union (EU) Common Position on Arms Exports and the Arms Trade Treaty as they apply to Dutch law, which outline criteria against which military exports must be assessed to determine the risk of abuse. The judgment made important findings on the nature of these risk assessments, which may have significant implications in future litigation.

The results of comparative studies on the fabrication and characterization of GaN/Ag substrates using pulsed laser deposition (PLD) and magnetron sputtering (MS) and their evaluation as potential substrates for surface-enhanced Raman spectroscopy (SERS) are reported. Ag layers of comparable thicknesses were deposited using PLD and MS on nanostructured GaN platforms. All fabricated SERS substrates were examined regarding their optical properties using UV–vis spectroscopy and regarding their morphology using scanning electron microscopy. SERS properties of the fabricated GaN/Ag substrates were evaluated by measuring SERS spectra of 4-mercaptobenzoic acid molecules adsorbed on them. For all PLD-made GaN/Ag substrates, the estimated enhancement factors were higher than for MS-made substrates with a comparable thickness of the Ag layer. In the best case, the PLD-made GaN/Ag substrate exhibited an approximately 4.4 times higher enhancement factor than the best MS-made substrate.

Kidney injury from antiangiogenic chemotherapy is a significant clinical challenge, and we currently lack the ability to effectively treat it with pharmacological agents. Thus, we set out to investigate whether simultaneous soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) inhibition using a dual sEH/COX-2 inhibitor PTUPB could be an effective strategy for treating antiangiogenic therapy-induced kidney damage. We used a multikinase inhibitor, sorafenib, which is known to cause serious renal side effects. The drug was administered to male Sprague-Dawley rats that were on a high-salt diet. Sorafenib was administered over the course of 56 days. The study included three experimental groups; 1) control group (naïve rats), 2) sorafenib group [rats treated with sorafenib only (20 mg/kg/day p.o.)], and 3) sorafenib + PTUPB group (rats treated with sorafenib only for the initial 28 days and subsequently coadministered PTUPB (10 mg/kg/day i.p.) from days 28 through 56). Blood pressure was measured every 2 weeks. After 28 days, sorafenib-treated rats developed hypertension (161 ± 4 mmHg). Over the remainder of the study, sorafenib treatment resulted in a further elevation in blood pressure through day 56 (200 ± 7 mmHg). PTUPB treatment attenuated the sorafenib-induced blood pressure elevation and by day 56, blood pressure was 159 ± 4 mmHg. Urine was collected every 2 weeks for biochemical analysis. After 28 days, sorafenib rats developed pronounced proteinuria (9.7 ± 0.2 P/C), which intensified significantly (35.8 ± 3.5 P/C) by the end of day 56 compared with control (2.6 ± 0.4 P/C). PTUPB mitigated sorafenib-induced proteinuria, and by day 56, it reduced proteinuria by 73%. Plasma and kidney tissues were collected on day 56. Kidney histopathology revealed intratubular cast formation, interstitial fibrosis, glomerular injury, and glomerular nephrin loss at day 56 in sorafenib-treated rats. PTUPB treatment reduced histological features by 30%-70% compared with the sorafenib-treated group and restored glomerular nephrin levels. Furthermore, PTUPB also acted on the glomerular permeability barrier by decreasing angiotensin-II-induced glomerular permeability to albumin. Finally, PTUPB improved in vitro the viability of human mesangial cells. Collectively, our data demonstrate the potential of using PTUPB or dual sEH/COX-2 inhibition as a therapeutic strategy against sorafenib-induced glomerular nephrotoxicity.

The research undertaken aimed to develop an efficient Pt-based catalyst for polymer electrolyte membrane fuel cells (PEMFCs) by using a cost-effective and efficient physical method to deposit platinum nanoparticles (PtNPs) on carbon supports directly from the platinum target. The method developed avoids the chemical functionalization of the carbon substrate and the chemical synthesis of PtNPs during catalyst fabrication. Platinum was deposited on carbon particles at room temperature using a pulsed laser deposition (PLD) system equipped with an ArF excimer laser (λ = 193 nm). The uniform deposition of PtNPs on carbon supports was achieved thanks to a specially designed electromechanical system that mixed the carbon support particles during platinum deposition. In the studies, Vulcan XC-72R carbon black powder, a popular material used as support in the anodes and cathodes of PEMFCs, and a porous carbon material with a high degree of graphitization were used as carbon supports. The best electrochemical measurement results were obtained for Pt deposited on Vulcan XC-72R. The peak power density measured for this material in a membrane electrode assembly (MEA) of a PEMFC (fed with H2/Air) was 0.41 W/cm2, which is a good result compared to 0.57 W/cm2 obtained for commercial 20% Pt Vulcan XC-72R. This result was achieved with three times less Pt catalyst on the carbon support compared to the commercial catalyst, which means that a higher catalyst utilization factor was achieved.

Hearing loss places a substantial burden on medical resources across the world and impacts quality of life for those affected. Further, it can occur peripherally and/or centrally. With many possible causes of hearing loss, there is scope for investigating the underlying mechanisms involved. Various signaling pathways connecting gut microbes and the brain (the gut-brain axis) have been identified and well established in a variety of diseases and disorders. However, the role of these pathways in providing links to other parts of the body has not been explored in much depth. Therefore, the aim of this review is to explore potential underlying mechanisms that connect the auditory system to the gut-brain axis. Using select keywords in PubMed, and additional hand-searching in google scholar, relevant studies were identified. In this review we summarize the key players in the auditory-gut-brain axis under four subheadings: anatomical, extracellular, immune and dietary. Firstly, we identify important anatomical structures in the auditory-gut-brain axis, particularly highlighting a direct connection provided by the vagus nerve. Leading on from this we discuss several extracellular signaling pathways which might connect the ear, gut and brain. A link is established between inflammatory responses in the ear and gut microbiome-altering interventions, highlighting a contribution of the immune system. Finally, we discuss the contribution of diet to the auditory-gut-brain axis. Based on the reviewed literature, we propose numerous possible key players connecting the auditory system to the gut-brain axis. In the future, a more thorough investigation of these key players in animal models and human research may provide insight and assist in developing effective interventions for treating hearing loss.

Energy transition towards a local resilient energy supply is necessary for energy security. Climate change and the threat of economic collapse are reasons to force society to become less dependent on fossil fuel. Small-scale solutions are expected to be more sustainable, as large-scale integrated networks are featured by complexity and difficult-to-notice vulnerabilities, creating system risks. This paper presents the results of empirical research among a sample of Polish business students (N = 205) on the importance of worldviews for the choice of the energy transition scenario (local solutions vs. large-scale solutions). Worldviews are represented here by the Dominant Social Paradigm (defined for the purpose of this study as the belief that liberal democracy, free markets, and technological development are to solve all type of problems). This study addresses two research questions: (1) Is there a difference in preference for the energy transition scenarios? (2) Does adherence to the Dominant Social Paradigm determine the choice of the scenario for energy transition? The results present a preference for non-cooperative solutions (individual household solutions and large-scale solutions), while no significant relation to the worldviews represented by the Dominant Social Paradigm has been found. The results suggest that preferences for individual and large-scale solutions may be influenced more by institutional factors than by personal worldviews. A policy implication is that a change in the socio-political institutions and strengthening local governance may be a prerequisite for a sustainable energy transition.

Currently, natural polymer materials with bactericidal properties are extremely popular. Unfortunately, although the biopolymer material itself is biodegradable, its enrichment with bactericidal compounds may affect the efficiency of biodegradation by natural soil microflora. Therefore, the primary objective of this study was to evaluate the utility of fungi belonging to the genus Trichoderma in facilitating the degradation of chitosan film modified with cinnamic acid and ellagic acid in the soil environment. Only two strains (T.07 and T.14) used chitosan films as a source of carbon and nitrogen. However, their respiratory activity decreased with the addition of tested phenolic acids, especially cinnamic acid. Addition of Trichoderma isolates to the soil increased oxygen consumption during the biodegradation process compared with native microorganisms, especially after application of the T.07 and T.14 consortium. Isolates T.07 and T.14 showed high lipolytic (55.78 U/h and 62.21 U/h) and chitinase (43.03 U/h and 41.27 U/h) activities. Chitinase activity after incorporation of the materials into the soil was higher for samples enriched with T.07, T.14 and the consortium. The isolates were classified as Trichoderma sp. and Trichoderma koningii. Considering the outcomes derived from our findings, it is our contention that the application of Trichoderma isolates holds promise for expediting the degradation process of chitosan materials containing bactericidal compounds.