We previously reported that mice with low neuronal pH drink more alcohol, demonstrating the importance of pH for alcohol reward and motivation. In this study, we tested whether systemic pH affects alcohol consumption and if so, whether it occurs by changing the alcohol reward. C57BL/6J mice were given NaHCO₃ to raise their blood pH, and the animals’ alcohol consumption was measured in the drinking-in-the-dark and two-bottle free choice paradigms. Alcohol consumption was also assessed after suppressing the bitterness of NaHCO₃ with sucrose. Alcohol reward was evaluated using a conditioned place preference. In addition, taste sensitivity was assessed by determining quinine and sucrose preference. The results revealed that a pH increase by NaHCO₃ caused mice to decrease their alcohol consumption. The decrease in high alcohol contents (20%) was significant and observed at different ages, as well as in both males and females. Alcohol consumption was also decreased after suppressing NaHCO₃ bitterness. Oral gavage of NaHCO₃ did not alter quinine and sucrose preference. In the conditioned place preference, NaHCO₃-treated mice spent less time in the alcohol-injected chamber. Conclusively, the results show that raising systemic pH with NaHCO₃ decreases alcohol consumption, as it decreases the alcohol reward value. Full article

The survival rate of cardiac arrest (CA) can be improved by utilizing percutaneous left ventricular assist devices (pLVADs) instead of conventional chest compressions. However, existing pLVADs require complex fluoroscopy-guided placement along a guidewire and suffer from limited blood flow due to their cross-sectional area. The recently developed self-expandable Impella CP (ECP) pLVAD addresses these limitations by enabling guidewire-free placement and increasing the pump cross-sectional area. This study evaluates the feasibility of resuscitation using the Impella ECP in a swine CA model. Eleven anesthetized pigs (73.8 ± 1.7 kg) underwent electrically induced CA, were left untreated for 5 min and then received pLVAD insertion and activation. Vasopressors were administered and defibrillations were attempted. Five hours after the return of spontaneous circulation (ROSC), the pLVAD was removed, and animals were monitored for an additional hour. Hemodynamics were assessed and myocardial function was evaluated using echocardiography. Successful guidewire-free pLVAD placement was achieved in all animals. Resuscitation was successful in 75% of cases, with 3.5 ± 2.0 defibrillations and 1.8 ± 0.4 mg norepinephrine used per ROSC. Hemodynamics remained stable post-device removal, with no adverse effects or aortic valve damage observed. The Impella ECP facilitated rapid guidewire-free pLVAD placement in fibrillating hearts, enabling successful resuscitation. These findings support a broader clinical adoption of pLVADs, particularly the Impella ECP, for CA. Full article

In this report we present seven lines of bioinformatic evidence supporting the conclusion that the Pentameric Ligand-gated Ion Channel (pLIC) Family is a member of the Voltage-gated Ion Channel (VIC) Superfamily. In our approach, we used the Transporter Classification Database (TCDB) as a reference and applied a series of bioinformatic methods to search for similarities between the pLIC family and members of the VIC superfamily. These include: (1) sequence similarity, (2) compatibility of topology and hydropathy profiles, (3) shared domains, (4) conserved motifs, (5) similarity of Hidden Markov Model profiles between families, (6) common 3D structural folds, and (7) clustering analysis of all families. Furthermore, sequence and structural comparisons as well as the identification of a 3-TMS repeat unit in the VIC superfamily suggests that the sixth transmembrane segment evolved into a re-entrant loop. This evidence suggests that the voltage-sensor domain and the channel domain have a common origin. The classification of the pLIC family within the VIC superfamily sheds light onto the topological origins of this family and its evolution, which will facilitate experimental verification and further research into this superfamily by the scientific community. Full article

The active vitamin D metabolites, 25-hydroxyvitamin D₃ (25D₃) and 1,25-dihydroxyvitamin D₃ (1,25D₃), are produced by successive hydroxylation steps and play key roles in several cellular processes. However, alternative metabolic pathways exist, and among them, the 4-hydroxylation of 25D₃ is a major one. This study aims to investigate the structure–activity relationships of 4-hydroxy derivatives of 1,25D₃. Structural analysis indicates that 1,4α,25(OH)₃D₃ and 1,4β,25(OH)₃D₃ maintain the anchoring hydrogen bonds of 1,25D₃ and form additional interactions, stabilizing the active conformation of VDR. In addition, 1,4α,25D₃ and 1,4β,25D₃ are as potent as 1,25D₃ in regulating the expression of VDR target genes in rat intestinal epithelial cells and in the mouse kidney. Moreover, these two 4-hydroxy derivatives promote hypercalcemia in mice at a dose similar to that of the parent compound. Full article

This study proposes a new optical system with the potential for time-lapse observation of living cellular tissue beyond the diffraction limit through speckle interferometry to facilitate biological research. The spatial resolution of this optical system was investigated and improved upon. This study also experimentally verified a finding from an earlier simulation study that the new super-resolution technology could be realised by analysing the phase distribution related to the shape of the measured object, preserved in the light reflected from the object. Additionally, a method was presented to confirm the positions of microstructures, based on the extracted characteristics of the structure. Full article

Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and murine CKDs. Comprehensive literature searches were conducted on five databases. Subgroup analyses of kidney diseases, sample types, disease stages, and species were conducted. A total of 38 human and 12 murine eligible studies were analyzed using Robust Rank Aggregation (RRA) and vote-counting analyses. Gene set enrichment analyses of miRNA signatures in each kidney disease were conducted using DIANA-miRPath v4.0 and MIENTURNET. As a result, top target genes, Gene Ontology terms, the interaction network between miRNA and target genes, and molecular pathways in each kidney disease were identified. According to vote-counting analysis, 145 miRNAs were dysregulated in human kidney diseases, and 32 were dysregulated in murine CKD models. By RRA, miR-26a-5p was significantly reduced in the kidney tissue of Lupus nephritis (LN), while miR-107 was decreased in LN patients’ blood samples. In both species, epithelial-mesenchymal transition, Notch, mTOR signaling, apoptosis, G2/M checkpoint, and hypoxia were the most enriched pathways. These miRNA signatures and their target genes must be validated in large patient cohort studies. Full article

The formation of solid deposits in the process of supercritical water gasification (SCWG) is one of the main problems hindering the commercial application of the process. Seven experiments were conducted with the grass Reed Canary Grass with different preheating temperatures, but all ended early due to the formation of solid deposits (maximum operation of 3.8 h). The position of solid deposits in the lab plant changed with the variation in the temperature profile. Since the formation of solid deposits consisting of salts, coke, and corrosion products is a severe issue that needs to be resolved in order to enable long-time operation, inner temperature measurements were conducted to determine the temperature range that corresponds with the zone of solid formation. The temperature range was found to be 400 to 440 °C. Wherever this temperature was first reached solid deposits occurred in the system that led to blockage of the flow. Additional to the influence of the temperature, the influence of the flow direction (up-flow or down-flow) on the operation of the continuous SCWG plant was examined. If salts are not separated from the system sufficiently, up-flow reactors should be avoided because they amplify the accumulation of solid deposits leading to a shortened operation time. The heating concept coupled with the salt separation needs to be redesigned in order to separate the salts before entering the gasification reactors. Outside of the determined temperature zone no deposition was visible. Thus, even though the gasification efficiency was low it could be shown that the operation was limited to the deposits forming in the heating section and not by incomplete gasification in the reactor where T > 600 °C. Full article

Introduction: Injuries of the anterior cruciate ligament (ACL) are commonly found in the general population, both among adult and pediatric patients, and their incidence has been increasing in recent years. Most of the late literature agrees that surgical reconstruction of the ACL is effective in improving long-term outcomes in pediatric patients, while others in the past have pleaded for non-surgical management. Purpose/Hypothesis: Our study aims to verify if ACL reconstruction (ACLR) using transphyseal technique in skeletally immature patients will provide angular deviations or growth restrictions. Study Design: Retrospective cohort study; Level of evidence 4. Methods: We perfomed a retrospective study to verify if transphyseal ACLR in children with less than or equal to 2 years of remaining growth leads to either limb length discrepancies or axis deviations. Results: Most patients who were treated using transphyseal technique showed significant improvements in their functional scores. There were statistically significant differences in lateral distal femoral angles (LDFA) and medial proximal tibial angles (MPTA), with no clinical impact. There was no significant limb length discrepancy (LLD) during the 2-year follow-up. Conclusions: Transphyseal ACLR is safe among children who have less than or equal to 2 years of remaining growth and brings no risk of axis deviations or limb length discrepancy. Full article

Alzheimer’s disease (AD) is characterized by a loss of neurons in the cortex and subcortical regions. Previously, we showed that the progressive degeneration of subcortical monoaminergic (MAergic) neurons seen in human AD is recapitulated in the APP_swe/PS1ΔE9 (APP/PS) transgenic mouse model. Because degeneration of cholinergic (Ach) neurons is also a prominent feature of AD, we examined the integrity of the Ach system in the APP/PS model. The overall density of Ach fibers is reduced in APP/PS1 mice at 12 and 18 months of age but not at 4 months of age. Analysis of basal forebrain Ach neurons shows no loss of Ach neurons in the APP/PS model. Thus, since MAergic systems show overt cell loss at 18 months of age, the Ach system is less vulnerable to neurodegeneration in the APP/PS1 model. We also examined whether the proximity to Aβ deposition affected the degeneration of Ach and 5-HT afferents. We found that the areas closer to the edges of compact Aβ deposits exhibit a more severe loss of afferents than the areas that are more distal to Aβ deposits. Collectively, the results indicate that the APP/PS model recapitulates the degeneration of multiple subcortical neurotransmitter systems, including the Ach system. In addition, the results indicate that Aβ deposits cause global as well as local toxicity to subcortical afferents. Full article

In this paper, we explore the trade-offs between public and private investment in autonomous driving technologies. Utilizing an evolutionary game model, we delve into the complex interaction mechanisms between governments and auto manufacturers, focusing on how strategic decisions impact overall outcomes. Specifically, we predict that governments may opt for strategies such as constructing and maintaining infrastructure for Roadside Infrastructure-based Vehicles (RIVs) or subsidizing high-level Autonomous Driving Vehicles (ADVs) without additional road infrastructure. Manufacturers’ choices involve deciding whether to invest in RIVs or ADVs, depending on governmental policies and market conditions. Our simulation results, based on scenarios derived from existing economic data and forecasts on technology development costs, suggest that government subsidy policies need to dynamically adjust in response to manufacturers’ shifting strategies and market behavior. This dynamic adjustment is crucial as it addresses the evolving economic environment and technological advancements, ensuring that subsidies effectively incentivize the desired outcomes in autonomous vehicle development. The findings of this paper could serve as valuable decision-making tools for governments and auto manufacturers, guiding investment strategies that align with the dynamic landscape of autonomous driving technology. Full article

Introduction: The impact of peripheral cytokine levels on the prognosis and treatment of immune checkpoint inhibitor (ICI) myocarditis has not been well studied. Objectives: This study aimed to identify cytokines that can prognosticate and direct the treatment of ICI myocarditis. Methods: This was a single-center, retrospective cohort study of patients with ICI myocarditis who had available peripheral cytokine levels between January 2011 and May 2022. Major adverse cardiovascular events (MACEs) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis, life-threatening arrhythmias, pulmonary embolism, and sudden cardiac death. Results: In total, 65 patients with ICI myocarditis had cytokine data available. Patients were mostly males (70%), with a mean age of 67.8 ± 12.7 years. Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were the most common cytokines to be elevated with 48/65 (74%) of patients having a peak IL-6 above normal limits (>5 pg/mL) and 44/65 (68%) of patients with peak TNF-α above normal limits (>22 pg/mL). Patients with elevated peak IL-6 had similar 90-day mortality and MACE outcomes compared to those without (10.4% vs. 11.8%, p = 0.878 and 8.8% vs. 17.7%, p = 0.366, respectively). Similarly, those with elevated peak TNF-α had similar 90-day mortality and MACEs compared to those without (29.6% vs. 14.3%, p = 0.182 and 13.6% vs. 4.8%, p = 0.413, respectively). Kaplan–Meier survival analysis also showed that there was not a significant difference between MACE-free survival when comparing elevated and normal IL-6 and TNF-α levels (p = 0.182 and p = 0.118, respectively). MACEs and overall survival outcomes were similar between those who received infliximab and those who did not among all patients and those with elevated TNF-α (p-value 0.70 and 0.83, respectively). Conclusion: Peripheral blood levels of IL-6 and TNF-α are the most commonly elevated cytokines in patients with ICI myocarditis. However, their role in the prognostication and guidance of immunomodulatory treatment is currently limited. Full article

In this paper, a novel method is demonstrated to sustain vehicle-to-vehicle (V2V) communication on curvy roads via the arrangement of the lateral position of a self-angle-adjustable mirror–reflective road sign (SAAMRS) and light-direction-sensing wide-angle complementary photodiodes (CPDs). Visible light communication (VLC) between vehicles attracts attention as a complementary technology to radio-frequency-based (RF-based) communication technologies due to its wide, license-free spectrum and immunity to interferences. However, V2V VLC may be interrupted on curvy roads due to the limited field of view (FOV) of the receiver or the line of sight (LOS) being interrupted. To solve this problem, an experiment was developed using an SAAMRS along with wide-angle light-direction-sensing CPDs that used a precise peak detection (PPD) method to sustain communication between vehicles in dynamic environments by rerouting the incident light with the highest signal intensity level to the receiver vehicle on curvy roads. We also used real images of curvy roads simulated as polynomials to calculate the necessary rotation angles for the SAAMRS and regions where communication exist. Our experimental results overlapped almost completely with our simulations, with small errors of approximately 4.8% and 4.4% for the SAAMRS angle and communication region, respectively. Full article

Electronic textiles (E-textiles) have experienced an increase in interest in recent years leading to a variety of new concepts emerging in the field. Despite these technical innovations, there is limited literature relating to the testing of E-textiles for some of the fundamental properties linked to wearer comfort. As such, this research investigates four fundamental properties of E-textiles: air permeability, drape, heat transfer, and moisture transfer. Three different types of E-textiles were explored: an embroidered electrode, a knitted electrode, and a knitted structure with an embedded electronic yarn. All of the E-textiles utilized the same base knitted fabric structure to facilitate a comparative study. The study used established textile testing practices to evaluate the E-textiles to ascertain the suitability of these standards for these materials. The study provides a useful point of reference to those working in the field and highlights some limitations of existing textile testing methodologies when applied to E-textiles. Full article

Even though Electric Powered Wheelchairs (EPWs) are a useful tool for meeting the needs of people with disabilities, some disabled people find it difficult to use regular EPWs that are joystick-controlled. Smart wheelchairs that use Brain–Computer Interface (BCI) technology present an efficient solution to this problem. This article presents a cutting-edge intelligent control wheelchair that is intended to improve user involvement and security. The suggested method combines facial expression analysis via a camera with EEG signal processing using the EMOTIV Insight EEG dataset. The system generates control commands by identifying specific EEG patterns linked to facial expressions such as eye blinking, winking left and right, and smiling. Simultaneously, the system uses computer vision algorithms and inertial measurements to analyze gaze direction in order to establish the user’s intended steering. The outcomes of the experiments prove that the proposed system is reliable and efficient in meeting the various requirements of people, presenting a positive development in the field of smart wheelchair technology. Full article

Society is showing a growing concern about the welfare of cetaceans in captivity as well as cetaceans in the wild threatened by anthropogenic disturbances. The study of the physiological stress response is increasingly being used to address cetacean conservation and welfare issues. Within it, a newly described technique of extracting cortisol from epidermal desquamation may serve as a non-invasive, more integrated measure of a cetacean’s stress response and welfare. However, confounding factors are common when measuring glucocorticoid hormones. In this study, we validated a steroid hormone extraction protocol and the use of a commercial enzyme immunoassay (EIA) test to measure cortisol concentrations in common bottlenose dolphin (Tursiops truncatus) and beluga (Delphinapterus leucas) epidermal samples. Moreover, we examined the effect of sample mass and body location on cortisol concentrations. Validation tests (i.e., assay specificity, accuracy, precision, and sensitivity) suggested that the method was suitable for the quantification of cortisol concentrations. Cortisol was extracted from small samples (0.01 g), but the amount of cortisol detected and the variability between duplicate extractions increased as the sample mass decreased. In common bottlenose dolphins, epidermal skin cortisol concentrations did not vary significantly across body locations while there was a significant effect of the individual. Overall, we present a contribution towards advancing and standardizing epidermis hormone assessments in cetaceans. Full article

In the search for a more effective chemotherapy for the treatment of Chagas’ disease, caused by Trypanosoma cruzi parasite, the use of gold compounds may be a promising approach. In this work, four gold(I) compounds [AuCl(HL)], (HL = bioactive 5-nitrofuryl containing thiosemicarbazones) were studied. The compounds were theoretically characterized, showing identical chemical structures with the metal ion located in a linear coordination environment and the thiosemicarbazones acting as monodentate ligands. Cyclic voltammetry and Electron Spin Resonance (ESR) studies demonstrated that the complexes could generate the nitro anion radical (NO₂⁻) by reduction of the nitro moiety. The compounds were evaluated in vitro on the trypomastigote form of T. cruzi and human cells of endothelial morphology. The gold compounds studied showed activity in the micromolar range against T. cruzi. The most active compounds (IC₅₀ of around 10 μM) showed an enhancement of the antiparasitic activity compared with their respective bioactive ligands and moderate selectivity. To get insight into the anti-chagasic mechanism of action, the intracellular free radical production capacity of the gold compounds was assessed by ESR and fluorescence measurements. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and redox cycling processes were characterized. The potential oxidative stress mechanism against T. cruzi was confirmed. Full article

Caves serve as time capsules, preserving significant markers of tectonic activity and offering insights into geological history. Fault geometries and past activations found in caves can be correlated with known deformational events in the broader area, temporally delimiting the speleogenesis. More specifically, cave passage formation is suggested to be affected by the regional stress-field. The Asprorema Cave in Northern Greece is a typical example of a fracture guided cave, with passage geometry influenced by relative sidewall movements, revealing these discontinuities as faults. This study constructs the timeframe and conceptual model of speleogenesis in relation to tectonic events, geomorphological evolution and hydrological zones, and verifies its relation to the stress-field. Active tectonics, mineralogy and cave geomorphology are investigated. Results suggest syntectonic speleogenesis under phreatic and epiphreatic conditions. The absence of corrosion on fault slip surfaces implies recent activations post cave’s shift to the vadose zone. Structural analysis identifies three main neotectonic phases: NNW-SSE striking faults (oldest group of structures), NE-SW striking faults with dextral strike-slip movement (post-middle Miocene), and NE-SW striking normal faults indicating extensional stress-regime (Quartenary). The last two phases affect cave passage shape causing wall displacement, highlighting passage formation along discontinuities perpendicular to the horizontal minimum stress axis. Full article

The synthesis of amphiphilic diblock and statistical (random) copolymers of poly(dimethylamino ethyl methacrylate) and poly((2-(diisopropylamino) ethyl methacrylate) using the reversible addition–fragmentation chain transfer polymerization technique (RAFT polymerization) is reported. The precursor copolymers were chemically modified to create derivative copolymers of polyelectrolyte and polyampholyte nature with novel solution properties. Moreover, their molecular and physicochemical characteristics, as well as their self-assembly in aqueous media as a function of molecular architecture and composition, are investigated by using size exclusion chromatography, spectroscopic characterization techniques and light scattering techniques. Furthermore, the behavior and properties of the obtained micelles and aggregates were studied, depending on the pH, temperature and ionic strength of the aqueous solutions. The response of the systems to changes in these parameters shows interesting behavior and new properties that are useful for their utilization as nanocarriers of pharmaceutical compounds. Full article

In this research work, a coated paper was prepared with poly (butylene adipate-co-terephthalate) (PBAT) film to explore its use in eco-friendly food packaging. The paper was coated with PBAT film for packaging using hot pressing, a production method currently employed in the packaging industry. The coated papers were evaluated for their structural, mechanical, thermal, and barrier properties. The structural morphology and chemical analysis of the coated paper confirmed the consistent formation of PBAT bi-layered on paper surfaces. Surface coating with PBAT film increased the water resistance of the paper samples, as demonstrated by tests of barrier characteristics, including the water vapor transmission rate (WVTR), oxygen transmission rate (OTR), and water contact angle (WCA) of water drops. The transmission rate of the clean paper was 2010.40 cc m⁻² per 24 h for OTR and 110.24 g m⁻² per 24 h for WVTR. If the PBAT-film was coated, the value decreased to 91.79 g m⁻² per 24 h and 992.86 cc m⁻² per 24 h. The hydrophobic nature of PBAT, confirmed by WCA measurements, contributed to the enhanced water resistance of PBAT-coated paper. This result presents an improved PBAT-coated paper material, eliminating the need for adhesives and allowing for the fabrication of bi-layered packaging. Full article

Soy isoflavones (SIF) are bioactive compounds with low bioavailability due to their poor water solubility. In this study, we utilized polymerized goat milk whey protein (PGWP) as a carrier to encapsulate SIF with encapsulation efficiency of 89%, particle size of 135.53 nm, and zeta potential of −35.16 mV. The PGWP-SIF nanoparticles were evaluated for their stability and in vitro digestion properties, and their ability to transport SIF was assessed using a Caco-2 cell monolayer model. The nanoparticles were resistant to aggregation when subjected to pH changes (pH 2.0 to 8.0), sodium chloride addition (0–200 mM), temperature fluctuations (4 °C, 25 °C, and 37 °C), and long-term storage (4 °C, 25 °C, and 37 °C for 30 days), which was mainly attributed to the repulsion generated by steric hindrance effects. During gastric digestion, only 5.93% of encapsulated SIF was released, highlighting the nanoparticles’ resistance to enzymatic digestion in the stomach. However, a significant increase in SIF release to 56.61% was observed during intestinal digestion, indicating the efficient transport of SIF into the small intestine for absorption. Cytotoxicity assessments via the MTT assay showed no adverse effects on Caco-2 cell lines after encapsulation. The PGWP-stabilized SIF nanoparticles improved the apparent permeability coefficient (Papp) of Caco-2 cells for SIF by 11.8-fold. The results indicated that using PGWP to encapsulate SIF was an effective approach for delivering SIF, while enhancing its bioavailability and transcellular transport. Full article

Recently, nonlinear fractional models have become increasingly important for describing phenomena occurring in science and engineering fields, especially those including symmetric kernels. In the current article, we examine two reliable methods for solving fractional coupled nonlinear Schrödinger models. These methods are known as the Sardar-subequation technique (SSET) and the improved generalized tanh-function technique (IGTHFT). Numerous novel soliton solutions are computed using different formats, such as periodic, bell-shaped, dark, and combination single bright along with kink, periodic, and single soliton solutions. Additionally, single solitary wave, multi-wave, and periodic kink combined solutions are evaluated. The behavioral traits of the retrieved solutions are illustrated by certain distinctive two-dimensional, three-dimensional, and contour graphs. The results are encouraging, since they show that the suggested methods are trustworthy, consistent, and efficient in finding accurate solutions to the various challenging nonlinear problems that have recently surfaced in applied sciences, engineering, and nonlinear optics. Full article

This study assesses the technical feasibility of a forward-osmosis-based system for concentrating produced water and extracting freshwater. Forward osmosis was combined with nanofiltration, the latter system used to restore the initial osmotic pressure of the diluted draw solutions while concurrently obtaining the final freshwater product. Three draw solutions, namely, MgCl₂, NaCl, and C₃H₅NaO₂, were initially tested against a synthetic water mimicking a pretreated produced water effluent having an osmotic pressure equal to 16.3 bar. MgCl₂ was thus selected for high-recovery experiments. Different combinations of draw solution osmotic pressure (30, 40, 60, 80, and 120) and draw-to-feed initial volume ratios (1, 1.6, and 2.2) were tested at the laboratory scale, achieving recovery rates between roughly 35% and 70% and water fluxes between 4 and 8 L m⁻²h⁻¹. One-dimensional, system-wide simulations deploying the analytical FO water flux equation were utilized to validate the experiments, investigate co-current and counter-current configurations, and understand the system potential. The diluted draw solutions were then transferred to nanofiltration to regenerate their original osmotic pressure. There, the highest observed rejection was 96.6% with an average flux of 21 L m⁻²h⁻¹, when running the system to achieve 100% relative recovery. Full article