Palmitoylethanolamide (PEA) has been prescribed for neuropathic pain for several years. This study is mainly addressed to summarize what has been published on the topic in the last decades, and how appropriate the numerous prescriptions are. Among others, it examines the innovative EquiPEA^® patent, which aims to address obstacles encountered with conventional PEA formulations. EquiPEA^® seems to partially ameliorate the bioavailability and the targeted distribution. It seems to introduce novel advancements that have the potential to enhance the therapeutic effectiveness of PEA in terms of its anti-inflammatory, antioxidant, and analgesic properties. The deep literature analysis aims to examine the potential advantages of this innovative formulation, in the context of several pathological conditions that may benefit from this molecule. In particular, it investigates the potential enhanced bioavailability and targeted delivery system of EquiPEA^®. Also, it tries to understand if it can modernize the field of therapy based on PEA, thus offering a better treatment option for individuals with long-term inflammation, oxidative stress, and neuropathic or mixed pain with a neuropathic component. The study examines the possible impact of EquiPEA^® on personalized medicine strategies and its potential for translation into clinical practice. It analyses the possibilities that EquiPEA^® has in enhancing patient outcomes in a range of central nervous system and inflammatory conditions. This narrative review makes a valuable contribution to the ongoing comprehension of PEA therapy. It establishes a foundation for further exploration in research and potential uses in clinical settings.

The effect of sonication on the molecular characteristics of poliacrylic acid (Carbopol® Ultrez 10) and its rheological behavior in aqueous dispersions and microgels containing 0.25 wt. % of the polymer was analyzed in this work by rheometry, weight-average molecular weight (Mw) measurements via static light scattering (SLS), Fourier transform infrared (FTIR) spectroscopy and confocal microscopy. For this, the precursor dispersion and the microgels were sonicated in a commercial ultrasound bath at constant power and different times. We observed a softening of the microgel microstructure consisting of a systematic decrease in its shear modulus, yield stress and viscosity with increasing sonication time, while their overall Herschel-Bulkley (H-B) behavior was preserved. SLS measurements evidenced a reduction of Mw of polyacrylic acid with sonication time. Separately, FTIR measurements indicate that sonication produces scission in the C-C links of the Carbopol® backbone, which results in chains with the same chemistry but lower molecular weight. Finally, confocal microscopy measurements revealed a concomitant diminution of the size of the microsponge domains with sonication time, which is reflected in a softer microstructure resulting from reduction of the molecular weight of polyacrylic acid. The present results indicate that both the microstructure and the rheological behavior of Carbopol® microgels, in particular, and complex fluids in general, may be manipulated or tailored by high-power ultrasonication.

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (>12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Reducing fertilizer-N rate, applying nitrification inhibitor (NI), and incorporating straw are widely recommended to improve N use efficiency of crops and decrease N losses. However, how these practices affect crop N uptake by regulating the fertilizer-N fate during the growing season is not well understood. We conducted a field 15N tracer study to explore the effectiveness of reduced N application, NI, and straw incorporation on fertilizer-N fates for maize cultivation in Northeast China. The following six treatments were used: 1) no N fertilization (control); 2) 200 kg urea-N ha−1 (100%N); 3) 200 kg urea-N ha−1 and 2400 kg dry-straw ha−1 (100%N+S); 4) 160 kg urea-N ha−1 (80%N, i.e., 20% reduction of N fertilization); 5) 160 kg urea-N ha−1 and nitrification inhibitor (Nitrapyrin) (80%N+NI); 6) 160 kg urea-N ha−1, nitrification inhibitor and 2400 kg dry-straw ha−1 (80%N+NI+S). Our results showed that the five N fertilization treatments yielded 16%–25% more grain and 39%–60% more crop N uptake than the control receiving no N fertilizer, but the differences among the five treatments were not statistically significant. In contrast to plant growth, changes in fertilizer-N fates in soil and plant pools were more pronounced. Compared with the 100%N treatment, 20% fertilizer-N reduction (80%N) decreased 15N concentration in topsoil and plant pools but increased the proportion of plant 15N recovery at harvesting (N use efficiency, NUE15N, 60% vs. 50%) (P < 0.05). Nitrapyrin co-application (80%N+NI) delayed soil nitrification and increased soil 15N retention at harvesting (52% vs. 36%), thereby decreasing NUE15N significantly (P < 0.05). Straw incorporation (100%N+S) decreased fertilizer-N retention compared with NI co-application because it promoted NUE15N significantly (P < 0.05). The combined application of NI and straw (80%N+NI+S) was more conducive to fertilizer-N retention in soil. Our findings demonstrate that NI and straw additions are efficient strategies for stabilizing fertilizer-N in soils and potentially minimizing N loss; however, their effects on NUE15N vary and the related mechanism must be further clarified in long-term trials.

In recent years, 360o videos have gained the attention of researchers investigating their educational potential. Given the ongoing debate about their impact on learning, particularly with young students where existing research is minimal, a comprehensive study was conducted to evaluate their effectiveness relative to other media forms. The study involved 44 kindergarten students learning about wild animals over nine sessions. The 360o videos were compared to printed materials and conventional videos to measure knowledge acquisition, motivation, enjoyment/positive feelings, immersion, and ease of use. The findings suggest that, compared to printed materials, 360o videos enhance knowledge acquisition. However, this advantage does not extend to comparisons with conventional videos. Similarly, while enjoyment and motivation were higher for 360o videos compared to printed materials, they did not surpass those associated with conventional videos. Despite their potential, 360o videos were deemed the least easy to use, likely due to the employment of low-cost HMDs. Immersion emerged as the only factor where 360o videos excelled, demonstrating a notable influence on learning outcomes. The implications of the study are also discussed.

The electronic nose (e-nose) is an innovative device that mimics the human olfactory system, allowing for the detection and identification of numerous scents. This abstract gives an in-depth examination of the current status of electronic nose technologies, with an emphasis on sensing mechanisms, applications, and recent breakthroughs. The research delves into the many uses of e-nose, such as food quality control, environmental monitoring, medical diagnostics, and industrial operations. It also covers the problems and potential future applications of electronic nose technology. The literature review highlights the importance of this technology in improving our capacity to evaluate complex scents in several domains.

The present work offers a contemporary synthesis of the application of the Oxford Nanopore^® MinION^™ within the context of cultural heritage biodeterioration investigations, while also providing a comprehensive discussion of possible future perspectives for their utilization in this research field. Owing to the distinctive characteristics of this device, the past few years have witnessed the consistent increase on the application of this system in a variety of cultural heritage materials. In fact, the technique has been useful to understand microbial biodeteriogens diversity and some of their metabolic and biodeteriogenic features. Considering the immense potential for application of this system, this manuscript explores and discusses further possibilities of the technique, focusing on helping understand critical questions on the cultural heritage biodeterioration area. Its application in various differential contexts, has opened doors for prospective applications on other interesting sub-areas of research meriting future investigations, including: biodeteriogens genome and transcriptome analysis, metatranscriptomics, biodeteriorative metabolism studies, inter and intra kingdom interactions analysis, resistome profiling, object history and context studies, in situ applications, bioprospecting and biotechnology.

Edible oils have commercial and nutritional value due to the presence of essential fatty acids. They can be consumed fresh in the form of capsules known as nutraceuticals. The quality of such products is of interest to the consumer. In this context, this study describes a method based on high resolution nuclear magnetic resonance (NMR) and Fourier transform mid-infrared spectroscopic analysis (FTIR), combined with statistical analyzes to differentiate different edible oils used as nutraceuticals in Brazil by fatty acid content. Through the analysis of 1H NMR spectra, the levels of saturated and unsaturated fatty acids in edible oils were characterized and quantified. Statistical analysis of the data confirmed the real distinction between nutraceutical raw materials, with emphasis on ω-9, ω-6 and ω-3 fatty acids. The analytical approach presented also demonstrated potential to identify the origin (animal or vegetable) of edible oils used as nutraceuticals.

Alignment of picornavirus proteinase/polymerase sequences reveals this family evolved into five ‘supergroups’. Interestingly, the nature of the 2A region of the picornavirus polyprotein is highly correlated with this phylogeny. Viruses within supergroup 4, the Paavivirinae, have complex 2A regions with many viruses encoding multiple 2A^NPGP sequences. In vitro transcription/translation analyses of a synthetic polyprotein comprising green fluorescent protein (GFP) linked to b-glucuronidase (GUS) via individual 2A^NPGPs showed two main phenotypes: highly active 2A^NPGP sequences - similar to Foot-and-Mouth Disease Virus 2A^NPGP and, surprisingly, a novel phenotype of some 2A^NPGP sequences which apparently terminate translation at the C-terminus of 2A^NPGP - without detectable re-initiation of downstream sequences (GUS). Probing databases with the short sequences between 2A^NPGPs did not reveal any potential ‘accessory’ functions. The novel, highly active, 2A-like sequences we identified substantially expands the toolbox for biomedical / biotechnological co-expression applications.

This study aimed to explore the genetic information about the yield traits in perennial Chinese rice "Shendao3^#" and provide a series of theoretical bases for the innovative utilization of perennial Chinese rice germplasm. The F₂ population derived from the cross between perennial Chinese rice "Shendao3^#" and one annual rice "XiqingzaoB" was developed to identify QTLs’ underlying yield-related traits. Fifteen yield traits including plant height, panicle plant^-1, and thousand-grain weight were measured for the QTL mapping. The software packages Excel 2010, GraphpadPrism 5.0, and QTLIciMapping 4.10 were used to perform the phenotypic data analysis, construction of molecular map, and QTL mapping, respectively. Results indicated 15 yield-related traits displaying normal distribution and belonging to quantitative trait inheritance. A total of 25 QTLs associated with the yield-related traits and 26 epistatic QTLs were detected on the whole genome except for the 6th and 12th chromosomes. This finding explained phenotypic variance with ranging from 4.21% to 27.30% and 1.15% to 19.30%, respectively. Six pleiotropic QTL (chromosomal regions) underlying two or more yield-related traits were detected on the 1st , 4th, 7th, 8th, and 11th chromosomes, respectively. Among 25 QTLs underlying a single yield-related trait, 11 were primarily identified in the perennial Chinese rice "Shendao3^#". All QTLs underlying 15 yield-related traits followed the genetic model of additive, dominant, and digenic epistatic of additive by additive, additive by dominant, dominant by additive, and dominant by dominant. This work can serve as a good foundation for yield-related gene mining and its utilization in breeding the perennial Chinese rice "Shendao3^#".

A novel Gram-stain-negative, facultatively anaerobic and mixotrophic bacterium, designated as strain LZ166T, was isolated from the bathyplagic seawater in the western Pacific Ocean. Cells were short rod-shaped, oxidase- and catalase- positive, and motile by means of lateral flagella. Growth of strain LZ166T was observed at 10-45 ℃ (optimum, 34-37 ℃), at pH 5-10 (optimum, 6-8) and in the presence of 0-5% NaCl (optimum, 1-3%). Phylogenetic analysis based on the 16S rRNA gene showed that strain LZ166T shared the highest similarity (98.58%) with Aquibium oceanicum B7T, and formed a distinct branch within the Aquibium genus. Genomic characterization, including average nucleotide identity (ANI, 90.73-76.79%), average amino identity (AAI, 88.50-79.03%) and digital DNA-DNA hybridization (dDDH, 36.1-22.2%) values between LZ166T and other species within the Aquibium genus, further substantiated its novelty. The genome of strain LZ166T was 6,119,659 bp in size with a 64.7 mol% DNA G+C content. The predominant fatty acid was summed feature 8 (C18:1ω7c and/or C18:1ω6c). The major polar lipids identified were Diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), glycolipid (GL) and phosphatidylglycerol (PG), with ubiquinone-10 (Q-10) as the predominant respiratory quinone. Genomic annotation indicated the presence of genes for a diverse metabolic profile, including pathways for carbon fixation via the Calvin–Benson–Bassham cycle and inorganic sulfur oxidation. Based on polyphasic taxonomic results, strain LZ166T represented a novel species of the genus Aquibium, for which the name Aquibium pacificus sp. nov., is proposed, with the type strain LZ166T (= MCCC M28807T = KACC 23148T = KCTC 82889T).

There has been an increased focus on new technologies to monitor habitat use and behaviour of cattle, to develop a more sustainable livestock grazing system, without compromising animal welfare. The currently most used method for monitoring cattle behaviour is tri-axial accelerometer data from systems such as virtual fencing technology or bespoke monitoring technology. This method requires high frequency data, and as such, quickly drains contemporary systems of power making it unsuitable for long-term monitoring. In this paper, we explore the possibility of determining habitat preference and habitat utilisation patterns in cattle, using low frequency activity and location data. We do this by (1) calculating habitat selection ratios, (2) determining daily activity patterns and based on those, (3) inferring grazing and resting sites in a group of cattle wearing virtual fencing collars in a coastal setting with grey, wooded and decalcified dunes, humid dune slacks and salt meadows. We found that GPS data, and a measure of activity, combined with accurate mapping of habitats can be an effective tool in assessing habitat preference. The animals preferred salt meadows over the other habitats, with wooded dunes and humid dune slacks being the least preferred. We were able to identify daily patterns in activity. By comparing general trends in activity levels to existing literature, it was possible to somewhat infer resting and grazing behaviour in the different habitats. According to our inference of behaviour the herd predominantly used the salt meadows for resting and ruminating. The approach used in this study allowed us to use GPS location data for measuring the activity and combine it with accurate habitat mapping in a cheap and effective way, which can be an important tool for guiding management decisions.

In this work, a ZIF-67/MWCNTs/Nafion sensor platform was constructed based on the good adsorption capacity of ZIF-67, the electrical conductivity of multiwalled carbon nanotubes (MWCNTs) and the excellent chemical stability of Nafion for the detection of Cu2+ in water. Meanwhile, the modified materials were characterized by scanning electron microscopy (SEM), Transmission electron microscopy (TEM), BET specific surface area test, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Fourier transform infrared spectrometry (FT-IR). Cyclic voltammetry (CV), electrochemical impedance (EIS), and square wave solvation voltammetry (SWSV) electrochemical methods were used to perform applied test studies on ZIF-67/MWCNTs/Nafion/GCE. The results show that ZIF-67/MWCNTs/Nafion/GCE has high sensitivity (57.5 μA/μM) and a low limit of detection (15.0 nM) for the electrochemical detection of Cu2+ ions in an electrochemical sensing system. It has high adsorption selectivity for Cu2+, and the recovery of Cu2+ in real water reached 98.6%-103%. The modified electrode has good repeatability, reproducibility, anti-interference, and stability, which makes this sensing platform can be practically applied to the detection of domestic water.

When it is in the template RNA, the naturally occurring m¹A epitranscriptomic RNA modification was recently reported to be able to stop the RNA polymerization reaction catalyzed by the RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. In this report, we report that m¹A via its triphosphate form (m¹ATP) can be incorporated into RNA by the same RdRp. These two findings point a new direction for antiviral drug development based on m¹A for combatting COVID-19. More broadly, it is possible that the large pool of epigenetic RNA as well as DNA modifications could serve as a treasury for drug discovery aimed at combating various infectious and other diseases.

Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, a potent inhibitor targeting the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interact with SARS-CoV-2 Mpro(A). Calculations using density functional theory have been instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding with a root mean square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.

PET imaging with [¹⁸F]F-DOPA has demonstrated high potential for the evaluation and management of pediatric brain gliomas. Manual extraction of PET parameters is time-consuming, lacks reproducibility, and varies with operator experience. In this study, we tested whether a semi-automated image processing framework could overcome these limitations. Pediatric patients with available static and/or dynamic [¹⁸F]F-DOPA PET studies were evaluated retrospectively. We developed a Python software to automate clinical index calculations, including preprocessing to delineate tumor volumes from structural MRI, accounting for lesions with low [¹⁸F]F-DOPA uptake. 73 subjects with treatment-naïve low and high-grade gliomas, who underwent brain MRI within two weeks of [¹⁸vF]F-DOPA PET, were included and analyzed. Static analysis was conducted on all subjects, while dynamic analysis was performed on 32 patients. For 68 subjects, the Intraclass Correlation Coefficient for T/S between manual and ground truth segmentation was 0.91. Using our tool, ICC improved to 0.94. Our method demonstrated good reproducibility in extracting static tumor-to-striatum ratio (p = 0.357), though significant differences were observed in tumor slope (p < 0.05). No significant differences were found in time-to-peak (p = 0.167) and striatum slope (p = 0.36). Our framework aids in analyzing [¹⁸F]F-DOPA PET images of pediatric brain tumors by automating clinical score extraction, simplifying segmentation and Time Activity Curve extraction, reducing user variability, and enhancing reproducibility.

Piezoelectric c-axis oriented zinc oxide (ZnO) thin films, from 1.8 up to 6.6 µm thick, have been grown by radio frequency magnetron sputtering technique onto fused silica substrates. A delay line consisting in two interdigital transducers (IDTs) with wavelength λ = 80 µm was photolith-ographically implemented onto the surface of the ZnO layers. Due to the IDTs split finger con-figuration and metallization ratio (0.5), the propagation of both the fundamental, third and nineth harmonic Rayleigh waves is excited; also, three leaky surface acoustic waves (SAWs) were detected travelling at velocity close to that of the longitudinal bulk wave in SiO2. The acoustic waves propagation in ZnO/fused silica was simulated by using 2D finite-element method (FEM) tech-nique to identify the nature of the experimentally detected waves. It turned out that, in addition to the fundamental and harmonic Rayleigh waves, also high-frequency leaky surface waves are ex-cited by the harmonic wavelengths; such modes are identified as leaky-Sezawa (LS) waves under cut-off. The velocity of all the modes was found in good agreement with the theoretically calcu-lated values. The existence of a low-loss region for the Sezawa wave below the cut off was theo-retically predicted and experimentally assessed.

The regulation of intracellular pH in yeast (Saccharomyces cerevisiae) cells is critical for cell function and viability. In yeast, protons (H+) can be excreted from cell by the plasma membrane ATPase Pma1 and pumped into vacuoles by the vacuolar H+-ATPase. Because Pma1 is critical to the survival of yeast cells, it is unknown whether other compensatory components are involved in the pH homeostasis in the absence of Pma1. To elucidate how intracellular pH is regulated independently of Pma1, we employed a screening approach by exposing the yeast haploid deletion mutant library (ver 4.0) to the selective plant plasma membrane H+-ATPase inhibitor PS-1, which we previously reported. After repeated screenings and verification, we identified two proteins, ALY1 and ALY2, that play a role in the regulation of intracellular pH when Pma1 is deficient. Our research uncovers a new perspective on the regulation of intracellular pH related to Pma1 and also preliminarily reveals a role for ALY1 and ALY2 in the regulation of intracellular pH.

Developing a dependable gas and condensate value chain is vital for the ongoing prosperity of the oil and gas industries. To achieve this, NNPC is enhancing its production facilities by employing process modeling and simulation with the assistance of Symmetry iCON®. As a part of this initiative, a simulation model was created using the Symmetry iCON® pipe plexus solver to simulate the dynamic environment of the gas and condensate pipeline network in the Nigerian Southern region. To validate the model, data from a single month, specifically December 2022, was utilized. Furthermore, the algorithm was utilized to generate projections for the month of January 2023, providing valuable insights into its effectiveness. The study also highlighted the significance of accurately estimating the characteristics and properties of a pseudo component of C6+ in relation to thermodynamics and material properties, which was a particularly insightful finding. he assessment of this property has transitioned from being relatively unimportant to becoming critically important, primarily due to the lack of condensate data monitoring at specific terminals. However, it's worth noting that the model currently has an error margin of 4-6% when predicting the data. As more information becomes available in the future, the model can be easily fine-tuned to better align with the actual conditions, allowing for more accurate predictions.

The construction of tunnels excavated by the conventional method in densely populated urban environments requires an adequate characterization of the loads acting on the primary lining during the excavation process to ensure that the ground is deformed and stresses around the tunnel are relieved, simultaneously complying with the failure and serviceability limits of international standards while minimizing damage to nearby structures. In this paper, common lining design criteria are revisited, through the numerical simulation of an instrumented tunnel section which is part of a 4.5 km long metro line currently under construction in Mexico City. Key needs for improvement in current design approaches are identified. The tunnel was instrumented with load cells, extensometers, and topographical references for convergences and divergences. A three-dimensional finite difference model of the instrumented section was developed, and the load transfer mechanisms between the excavated soil and the primary lining was analyzed. Then, the numerical simulation of the contribution of the secondary lining in the overall stability for sustained load was established, along with the expected ground settlements, which can significantly affect nearby structures. Results gathered from this research are key for updating lining design criteria for urban tunnels built in stiff brittle soils.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

The control of classical swine fever (CSF) in endemic areas has been attempted with modified live vaccines. However, in some regions, the implementation of imperfect vaccination programs has led to a reduction in the genetic diversity of the circulating strains and a change in their virulence. Porvac® subunit vaccine has been shown to provide a rapid onset of protection against the “Margarita” strain. The aim of this study was to evaluate whether the immune response induced by Porvac® is also effective against autochthonous isolates of low, medium or high virulence. All pigs vaccinated with Porvac® were protected against the disease after the challenge. PR-11/10–3 isolate caused a very mild disease in controls, whilst Holguin_2009 isolate produced mild to moderate signs of CSF and one of the pigs died. Finally, controls inoculated with PR-2016 isolate developed moderate to severe signs of CSF and two of them died. Viral replication was detected in controls, but not in pigs immunized with Porvac®. Finally, anti-Erns antibodies were induced in five out of six control pigs but in any of the vaccinated pigs. These results support the use of Porvac® for the control and elimination of CSF in Cuba and other endemic regions.

Polymer-based composites are widely used in the automotive, security, aeronautical and space industries, to mention a few. This is because of their good mechanical properties, which are similar to those of metals but with the attraction of being lightweight. Kevlar® as a reinforcement is extensively used in the security industry owing to its good ballistic properties. This investigation presents the mechanical characterization based on in-plane quasi-static tensile testing of Kevlar® composite using a universal testing system. The methodology developed for the preparation of coupons is based on pressure, temperature and time. As a result of this work, elastic moduli (EL and ET), Poisson’s ratio (νLT), shear modulus (GLT) and strengths (XT, YT, S) were obtained. It is worth mentioning that there is scarce or no characterization of this material in the literature, and those studies that do characterize it do not present the coupon thermoforming conditions or the reasons of the specimen dimensions (width, length and thickness).

Hydrodechlorination reaction of 3-(benzo-1,3-dioxol-5-yl)-3-chloro-2-methylacrylaldehyde in the presence of different low metal content heterogeneous mono- or bi-metallic catalysts was tested for the synthesis of the fragrance Helional® (3-[3,4-methylendioxyphenyl]-2-methyl-propionaldehyde). In particular, mono Pd/Al2O3, Rh/Al2O3 or bi-metallic Pd-Cu/Al2O3, Rh-Cu/Al2O3 catalysts were tested in different reaction conditions from which it emerged that mono-Rh/Al2O3 was the best performing catalyst allowing to achieve 100% substrate conversion and 99% selectivity towards Helional® in 24h at 80°C, p(H2) 1.0 MPa in the presence of a base. To establish correlations between atomic structure and catalytic activity, catalysts were characterized by Cu, Rh and Pd K-edge XANES, EXAFS analysis. These characterizations allowed to verify that the formation of Pd-Cu alloys and the presence of Cu oxide/hydroxide species on the surface of the Al2O3 support, are responsible for the very low catalytic efficiency of bimetallic species tested.

1) Background: Patients with neurological disorders are particularly at risk of falling and requiret functional rehabilitation. HUBER® is a motorised rotating platform that allows simultaneous work on balance, stability and strength with continuous adaptation and immediate feedback. This study aimed to measure the impact of rehabilitation with the HUBER® on the physical performance and quality of life of patients with neurological diseases requiring functional rehabilitation. 2) Methods: 32 subjects were enrolled in CHU Liège CNRF and randomly divided into 2 groups. The first group received classical rehabilitation combined with two training sessions per week on the HUBER® for 8 weeks. The second group received their usual treatment. This randomized control trial has been registered on clinicaltrials.gov under the number NCT04687293. Physical performance and quality of life were evaluated at different time. 3) Results: There was no significant difference between the 2 groups after enrolment. In terms of physical performance, an improvement in SPPB chair stand test (p=0.021) and total SPPB (p=0.003) was observed in the HUBER® group. In terms of quality of life, a higher improvement was observed overall in the HUBER® group (p&lt;0.05 between groups). 4) Conclusion: The HUBER® showed promising results in functional rehabilitation of patients with neurological pathologies, as a complement to classical rehabilitation management by physiotherapy.

Enhancing the acoustical quality in learning environments is mandatory, especially for Hearing Aids (HAs) users. When in-field evaluations cannot be performed, Virtual Reality (VR) can be adopted for the acoustical quality assessment of existing and new buildings, contributing to the acquisition of subjective impressions in lab settings. To ensure an accurate spatial reproduction of the sound field in VR also for HAs users, multispeaker-based systems can be employed to auralize a given environment. However, most systems are effortful due to costs, size and construction. This work deals with the validation of a VR-system based on a 16-speaker-array synced with a VR-headset, arranged to be easily replicated in small non-anechoic spaces and suitable for HAs users. Both objective and subjective validations are performed against a real university lecture room of 800 m3 and with 2.3 s of Reverberation Time at mid-frequencies. Comparisons of binaural and monoaural room acoustic parameters are performed between measurements in the real lecture room and its lab reproduction. To validate the AudioVisual experience, 32 normal-hearing subjects were administered the Igroup Presence Questionnaire (IPQ) on the overall sense of perceived presence. The outcomes confirm that the system is a promising and feasible tool to predict the perceived room acoustical quality.

Background: Existing human cell immortalization methods made the cells obtain oncogenesis phenotype and/or caused the cells gain and/or lose chromosomes. Immortalized normal human T cells lines provide critical in vitro models for basic research and therapeutic products development.Methods: We utilized a CRISPR/Cas9 system to replace a single copy of the exon 2 of the cell cycle inhibitor gene CDKN2A (encoding p16 and p14 proteins) with a single copy of human telomerase reverse transcriptase (hTERT) to immortalize human primary CD8⁺ T cells (hCD8⁺T-TERT). By using Cas9 protein and low donor DNA copies/cell, we successfully immortalized hCD8⁺T cells with a single copy of hTERT transgene, which also avoided uncontrolled insertion of Cas9 gene and guide RNA vector.Results: Human primary CD8+ cells were immortalized and expanded more than 2.6 × 10⁷ times. Characterization of the cells revealed that the immortalized CD8⁺ T-TERT cells retained most of the cell surface markers and normal karyotype. The CD8⁺ T-TERT cells also retained the dependence of IL-2 and CD3/CD28 activator for survival and expansion.Conclusion: we established a stable immortalized CD8⁺ T cell line that had a phenotype consistent with T cells and will be a useful research model.

Manganese porphyrins reportedly exhibit synergic effects when combined with irradiation. However, an in-depth understanding of intratumoral heterogeneity and immune pathways, as affected by Mn porphyrins, remains limited. Here, we explored the mechanisms underlying immunomodulation of a clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001, MnBuOE), using single-cell analysis in murine carcinoma model. Mice bearing 4T1 tumors were divided into 4 groups: control, MnBuOE, radiotherapy (RT), combined MnBuOE and radiotherapy (MnBuOE/RT). In epithelial cells, epithelial-mesenchymal transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related genes were significantly downregulated in the MnBuOE/RT compared to the RT. All subtypes of cancer-associated fibroblasts (CAFs) were clearly reduced in MnBuOE and MnBuOE/RT. Inhibitory receptor-ligand interactions, in which epithelial cells and CAFs interacted with CD8+ T cells, were significantly lower in the MnBuOE/RT than in the RT. Trajectory analysis showed that DC maturation-associated markers were increased in MnBuOE/RT. M1 macrophages were significantly increased in the MnBuOE/RT compared to the RT, whereas myeloid-derived suppressor cells were decreased. CellChat analysis showed that the number of cell-cell communications was the lowest in the MnBuOE/RT. Our study is the first to provide evidence for the combined radiotherapy with a novel Mn porphyrin clinical candidate, BMX-001 from the perspective of each cell-type within the tumor microenvironment.

Solar electric and solar thermal energies are often considered as part of the solution to the current energy emergency. In the present work, a study of the characteristic length of tubes in flat photovoltaic-thermal (PVT) hybrid solar devices has been carried out using three heat transfer fluids: water, Emim-Ac ionic liquid and ionanofluid of graphene nanoparticles suspended in the above ionic liquid. Experimental measurements and numerical simulations have been performed using the HEATT® platform. Slower fluid velocities are recommended if high fluid outlet temperatures are the goal of the application, but this penalizes the overall thermal energy production. The characteristic process length, or most efficient distance at which heat transfer occurs, is not typically achieved in parallel tube PVT collectors; coil-type panels can improve the thermal and temperature performance of INFs in PVT solar collectors depending on the application.

Groundnut is an important cash crop and a diet component for rural households in sub-Saharan Africa. However, Aflatoxin contamination remains a barrier to promoting groundnut-based food products as food levels above maximum limit (ML) can adversely affect human health. Three objectives were set, namely, (i) to characterize the post-harvest operations and risk factors affecting aflatoxin contamination, (ii) to assess aflatoxin incidence in on-farm stores and, iii) to assess agronomic practices that can be integrated to improve yield and reduce aflatoxin contamination. The average aflatoxin levels in on-farm stores were 11.3-16.4μg/kg, in which the proportions of ML were 25.7% at 4μg/kg, 56.3% at 15μg/kg, and 80% at 20μg/kg (~5-7 months after harvest). The application of Aflasafe® resulted in safe or no aflatoxin contamination across the locations. Significant hazards identified during postharvest operations include intermittent rain at harvest and drying (6.5), insect pests attacks after harvest (6), prolonged harvest to stripping interval (6.6), drying on bare ground (6.2), storing on bare floor (6.9), use of poorly efficient shelling machines (6.5), and re-use of rejected nut (6.1). This study provides solutions to minimize aflatoxin risk if appropriate technologies (e.g. improved variety, fertilizer, rhizobia inoculant, and Aflasafe®) and policies are deployed.

GeneVac-B® was recently licensed in Burkina Faso and is widely used for population vaccination. This study aimed to evaluate the immune response in people fully vaccinated against hepatitis B with the GeneVac-B® vaccine in Burkina Faso under actual conditions of use. This cross-sectional study included individuals fully vaccinated with GeneVac-B®. For each consenting participant, sociodemographic and clinical data were collected using a structured questionnaire. Approximately 4 mL of whole blood was collected for immunological (anti-HBs, HBsAg, anti-HCV and anti-HIV) and biochemical (blood glucose, total cholesterol, and triglycerides) testing. The anti-HBs titer was used to determine the immune response. A total of 392 participants were included in the study. The mean age was 35.5±15 years. Approximately 56.1% had been previously exposed to HBV. Three hundred eighty (380) participants had an anti-HBs titer ≥ 12 mIU/mL, a seroprotection rate of 96.9%, and 12 had a titer &lt; 12 mIU/mL, a nonresponse rate of 3.1%. Among the nonresponders, 11 (11/12; 91.7%) had high total cholesterol levels (&gt; 240 mg/dL), and 8 (8/12; 66.7%) were older than 40 years of age. The results showed an excellent immune response to GeneVac-B® in our study population. However, age &gt; 40 and high total cholesterol appear to be factors associated with nonresponse.

Preoperative assessment is crucial in surgical care, traditionally relying on physical examinations and paper-based questionnaires. The emergence of digital tools like Pathpoint® ePOA represents a significant advancement, aiming to enhance the efficiency, accuracy, and standardisation of preoperative evaluations. Pathpoint® ePOA is a cloud-based platform designed to integrate seamlessly with Electronic Health Records (EHRs), providing a comprehensive, data-driven approach to preoperative assessments. It supports improved risk stratification, optimised resource allocation, and enhanced patient engagement through features such as customisable templates and real-time data integration.Current research highlights that digital preoperative tools like ePOA offer notable advantages, including increased clinical capacity, better complexity stratification, and improved patient follow-up. Despite these benefits, gaps remain in comparative studies, detailed clinical outcomes, and patient engagement strategies, indicating areas for further exploration. Pathpoint® ePOA adheres to rigorous safety standards and risk management protocols, ensuring reliability and data security while contributing to improved surgical outcomes. The benefit-risk ratio for ePOA is favourable, underscoring its potential to advance preoperative care by optimising clinical workflows and enhancing patient safety.

The novel phosphor Eu3+ doped Na5Zn2Gd(MoO4)6 triple molybdate were prepared by the sol-gel method. The structure, morphology, and luminescent properties have been characterized by X-ray diffraction, thermogravimetry-differential thermal analysis, scanning electron microscopy, FTIR spectroscopy and Luminescence spectroscopy. The results indicated that the synthesized Na5Zn2Gd1-x(MoO4)6: xEu3+phosphor consisted of a pure phase with monoclinic structure. Under excitation at 465 nm, the Na5Zn2Gd1-x(MoO4)6: xEu3+ phosphor exhibits intensive red emission band around 610 nm corresponding to the transition of 5D0→7F2 is much higher than that 5D0→7F1 at 594 nm, which was appropriate for blue LED. According to the influence of the synthesis conditions, the phosphors show the highest emission intensity as the doping concentration of Eu3+ was 25 mol.% and the molar ratio of citric acid to metal ions was 2:1. Na5Zn2Gd0.75(MoO4)6: 0.25 Eu3+ with the color coordinates (x= 0.658, y= 0.341) is a stable red phosphor for blue-based white LEDs due to it is closer to the NTSC standard values (0.670, 0.330) comparing with the color coordinates (0.48, 0.50) of the commercial Y2O2S: Eu3+ red phosphor.

Introduction: Urinary tract infections (UTIs) are a significant global health issue, especially among women, with growing concerns related to antibiotic resistance and adverse effects. The Uromune® vaccine, a sublingual bacterial lysate, represents a promising therapeutic alternative by enhancing immune responses against uropathogens. Methods: This retrospective study, conducted at Hospital Universitari de Sant Joan de Reus from January 2017 to August 2022, evaluated the effectiveness of Uromune® in treating recurrent UTIs (rUTIs). Patients received personalized autovaccines administered as two sublingual puffs daily for three months. Clinical, microbiological, and demographic data were analyzed to assess treatment outcomes and identify recurrence-associated factors. Results: Forty-nine patients (mean age, 61 years, and 59.2% women) were included in the study. Uromune® treatment decreased UTI episodes, from 3.73 ± 0.97 the year before to 0.98 ± 1.36 (P &lt; 0.001) the year after its administration. The number of patients who suffered three or more episodes per year dropped from 43 (87.7%) before the intervention to 7 (14.3%) afterward. The maximum effectiveness of the autovaccine was observed three months post-administration, with 44 patients not experiencing any UTI episodes. Regression analysis identified having had a urostomy, chronic kidney disease, and being immunosuppressed as predictors of recurrence. Conclusion: The Uromune® autovaccine effectively reduced the frequency of rUTIs and associated hospitalizations, offering substantial relief to patients. These findings support the integration of Uromune® into routine clinical practice as a viable alternative to conventional antibiotic treatments.

Interpolyelectrolyte complexes Eudragit® EPO/L100 received in different pH were characterized by different degree of swelling in mimicking fasted stomach medium (0.1 M HCl) and saved their shape during 6 hours of the experiment. The microenvironmental changes in IPECs structure during swelling testing were inves-tigated using FT-IR spectroscopy, thermal and elemental analysis. Both samples of IPECs during swelling were transformed to a similar structure with approximately the same composition. IPEC samples showed bioadhesive properties that was not significantly different from the positive control (Carbopol) in the test with the mucin compacts. The release rate of metronidazole (class I BCS) from IPEC matrices increased with the increasing degree of swelling. IPEC 1 provided 49.62 ± 6.20% and IPEC 2 – 87.69 ± 5.15 % of metronidazole release after 6 hours in mimicking fasted stomach medium (0.1 M HCl). Total amount of released acyclovir (class III BCS) from IPEC 1 was 25.76 ± 5.67 % and from IPEC 2 was 21.48 ± 5.00 %. Release of both drugs was controlled by relaxation of polymeric chains in matrices according to the Peppas-Sahlin model. According to the received results, investigated interpolymer complexes are perspective for further evalua-tion as carriers for gastroretentive bioadhesive systems.

This study proposes a flexible and adaptable protocol for the establishment of agricultural management zones that utilises remote sensing, ground truthing (apparent electrical conductivity and soil sampling), the IRRIGOPTIMAL® system and machine learning. This protocol could contribute significantly to the rational use of inputs (water, fertilizers and pesticides) and to the further efficient development of an optimal irrigation system with variable irrigation rates. The methodology to develop this protocol was applied to olive and alfalfa plots in Heraklion (Crete, Greece) to monitor soil and crop responses for the period 2022-2024. Spatial and temporal assessment of selected soil and plant parameters (moisture, photosynthetic activity) using ground and vegetation reflectance mapping by satellites and unmanned aerial systems provides important information in both the pre- and main phases of the management zone delineation. Geophysical methods such as electromagnetic induction, applied in the main phase of management zone delineation, provide a robust technique to determine the spatial and temporal distribution of apparent electrical conductivity. The Random Forest machine learning model was found to be most suitable for predicting soil electrical conductivity based on satellite-derived salinity indices and ground electromagnetic induction. Finally, the IRRIGOPTIMAL® system provides real-time monitoring of a variety of weather and soil parameters to determine the optimal cultivation of crops based on the creation of agricultural management zones.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

Sour waters are one of the main aqueous byproducts generated during petroleum refining and require processing in Sour Water Treatment Units (SWTUs) to remove contaminants such as H₂S and NH₃ in compliance with environmental legislations. Therefore, monitoring the composition of SWTU effluents, including acid gas, ammoniacal gas, and treated water, is essential. This study aims to present an AI (artificial intelligence) hybrid-based methodology to develop soft sensors capable of real-time prediction of H₂S and NH₃ mass fractions in the effluents of SWTUs and validate them using real data from industrial units. Initially, a new database based on the dynamic simulation of a two stripping columns SWTU phenomenological model, developed in Aspen Plus Dynamics® V10, was generated, aiming at non-faulty runs, unlike our previous work [1]. Ensemble methods (Decision Trees), such as Gradient Boosting and Random Forest, and Support Vector Machines were compared for soft sensor creation using these simulated data. The best outcome was the development of six soft sensors based on Random Forest with R² greater than 0.87, MAE less than 0.12, MSE less than 0.17, and RMSE less than 0.41. Variable importance analysis revealed that the temperature of the second stage of Column 1 significantly influences the thermodynamic equilibrium of H₂S and NH₃ separation from sour waters, being critical for five of the six soft sensors. After this initial stage using data from the phenomenological model, data from an industrial-scale SWTU were used to develop real soft sensors. The results proved the effectiveness of the conjugated use of physical model and industrial data approach in the development of soft sensor for two-column SWTUs.

Among all the active confinement techniques, the use of pre-tensioned stainless steel straps has recently gained much attention. The flexibility of the stainless steel straps allows us to bend and pass them through the thickness of the masonry, thus creating a three-dimensional strengthening system between the two opposite facings. The use of the same perforation for the passage of several straps closed in a loop generates a continuous strengthening system that prevents parts of the structure from falling and injuring the occupants during seismic events. However, the perforations can nullify the in-plane strengthening, as they act as cylindrical hinges and make the reinforcement system labile for certain strap arrangements. Diagonal compression tests on square masonry panels performed in the present study show that the straps improve neither strength nor ductility when running along the mortar head and bed joints, arranged in square meshes. Conversely, they improve both strength and ductility when the straps make angles of 45° with the mortar joints. Furthermore, the experimental results show that the straps exert an anisotropic effect that decreases the apparent in-plane Poisson ratio. They also provide new insights into the diagonal compression test and allow formulating a new proposal for the pseudo-ductility factor.

Abnormal platelet functions are associated with human morbidity and mortality. Maintaining physiological platelet function is critical to hemostasis and preventing platelet-associated diseases such as cardiovascular disease, cancer metastasis, immune disorders, hypertension, diabetes, sickle cell disease, inflammatory bowel disease, sepsis, rheumatoid arthritis, myeloproliferative disease, and Alzheimer’s disease. Platelets become hyperactive in obesity, diabetes, a sedentary lifestyle, hypertension, pollution, and smokers. Platelets, upon activation, can trawl leukocytes and progenitor cells to the vascular injury sites. Platelets also release various pro-inflammatory, anti‐inflammatory, and angiogenic factors and shed microparticles in the circulation. The challenge for therapeutic intervention in these diseases will be identifying factors that preferentially block specific targets involved in platelets' complex contribution to inflammation or tumor progression while leaving their hemostatic function at least partially intact. Since antiplatelet drugs such as aspirin are not recommended as primary preventives, it is essential to use alternative safe platelet inhibitors. Potent natural antiplatelet factors were investigated, including n-3 fats, polyphenols, and other bioactive compounds. This review describes the anti-platelet bioactive compounds in food that can prevent platelet hyperactivity and thus may prevent several platelet-mediated diseases, including cardiovascular disease.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.