Within the scope of observed materialistic physical systems, without addressing the roots of H-Bar and big G, it is impossible to construct a workable model of final unification. With reference to our earlier proposed three large atomic gravitational constants, it is possible to reform and compactify the 10 dimensional String theory to 3+1 dimensions

Plants are constantly exposed to a variety of different environmental stresses, including drought, salinity, and elevated temperatures. These stress cues are assumed to aggravate in the future driven by the global climate change scenario which we are currently experiencing. These stressors have largely detrimental effects on plant growth and development and, therefore, put global food security in jeopardy. For this reason, it is necessary to expand our understanding of the underlying mechanisms by which plants respond to abiotic stresses. Especially boosting our insight into the ways by which plants balance their growth and their defense programs appears to be of paramount importance, as this may lead to novel perspectives that can pave the way to increase agricultural productivity in a sustainable manner. In this review, our aim was to present a detailed overview of different factettes of the crosstalk between the antagonistic plant hormones abscisic acid (ABA) and auxin, two phytohormones that are the main drivers of plant stress responses, on the one hand, and plant growth, on the other.

This research investigates the potential application of generative language models, especially ChatGPT, in aviation safety analysis as a means to enhance the efficiency of safety analyses and accelerate the time it takes to process incident reports. In particular, ChatGPT was leveraged to generate incident synopses from narratives, which were subsequently compared with ground truth synopses from the Aviation Safety Reporting System (ASRS) dataset. The comparison was facilitated by using embeddings from Large Language Models (LLMs), with aeroBERT demonstrating the highest similarity due to its aerospace-specific fine-tuning. A positive correlation was observed between synopsis length and their cosine similarity. In a subsequent phase, human factor issues involved in incidents as identified by ChatGPT were compared to human factor issues identified by safety analysts. A concurrence rate of 61% was found, with ChatGPT demonstrating a cautious approach towards attributing human factor issues. Finally, the model was used to attribute incidents to relevant parties. As no dedicated ground truth column existed for this task, a manual evaluation was conducted. ChatGPT attributed the majority of incidents to the Flight Crew, ATC, Ground Personnel, and Maintenance. This study opens new avenues for leveraging AI in aviation safety analysis.

G‐quadruplexes (G4) are structures formed at the ends of the telomere, these are rich in guanines and were stabilized by molecules that bind to specific sites. TMPyP4 and Thymoquinone (TQ) are small molecules that bind to the G4, they have drawn attention because of their role as telomerase inhibitors. The aim of this study was to evaluate the effects of telomerase inhibitors on cellular proliferation, senescence, and death. Two cell lines LC‐HK2 (NSCLC) and RPE‐1 were treated with TMPyP4 (5μM) and TQ (10μM). Both inhibitors were effective in decreasing telomerase activity. TMPyP4 increased the percentage of cells with membrane damage associated with cell death and decreased the frequency of cells in the S‐phase. TMPyP4 changed the cell adhesion ability and modified the pattern of focal adhesion. TQ acted in a dose‐dependent manner, increasing the frequency of senescent cells, and inducing cell cycle arrest in the G1. In conclusion, the effects of both drugs on LC-HK2 and RPE-1 cell lines were different although both are telomerase inhibitors, because TMPyP4 decreased proteins of cell adhesion and TQ induces a decrease in cell viability.

(1) Background: Artificial Intelligence (AI) models have shown potential in various educational contexts. However, their utility in explaining complex biological phenomena, such as Intrinsically Disordered Proteins (IDPs), requires further exploration. This study empirically evaluated the performance of various Large Language Models (LLMs) in the educational domain of IDPs. (2) Methods: Four LLMs, GPT-3.5, GPT-4, GPT-4 with Browsing, and Google Bard (PaLM 2), were assessed using a set of IDP-related questions. An expert evaluated their responses across five categories: accuracy, relevance, depth of understanding, clarity, and overall quality. Descriptive statistics, ANOVA, and Tukey's honesty significant difference tests were utilized for analysis. (3) Results: The GPT-4 model consistently outperformed the others across all evaluation categories. Although GPT-4 and GPT-3.5 were not statistically significantly different in performance (p>0.05), GPT-4 was preferred as the best response in 13 out of 15 instances. The AI models with browsing capabilities, GPT-4 with Browsing and Google Bard (PaLM 2) displayed lower performance metrics across the board with statistically significant differences (p<0.0001). (4) Conclusion: Our findings underscore the potential of AI models, particularly LLMs such as GPT-4, in enhancing scientific education, especially in complex domains such as IDPs. Continued innovation and collaboration among AI developers, educators, and researchers are essential to fully harness the potential of AI for enriching scientific education.

Consistent calibration and monitoring is a basic prerequisite for providing reliable time series of global and regional sea level variations from altimetry. The precision of sea level measurements and regional biases for six altimeter missions (Jason-1/2/3, Envisat, Saral, Sentinel-3A) is assessed at eleven GNSS-controlled tide gauge stations in the German Bight (SE North Sea) for the period 2002 to 2019. The gauges are partly located at the open water, partly at the coast close to mudflats. The altimetry is extracted at virtual stations with distances from 2 to 24 km from the gauges. The processing is optimized for the region and adjusted for the comparison with instantaneous tide gauges readings. An empirical correction is developed to account for mean height gradients and slight differences of the tidal dynamics between gauge and altimetry which improves the agreement between the two data sets by 15-75%. The precision of the altimeters is depending on location and mission and is shown to be at least 1.8 to 3.7 cm based on an assumed precision of 2 cm for the gauges. The accuracy of the regional mission biases is strongly dependent on the mean sea surface heights near the stations. The most consistent biases are obtained based on the CLS2011 model with mission dependent accuracies from 1.3 to 3.4 cm. Hence, the GNSS-controlled tide gauges operated operationally by WSV might complement the calibration and monitoring activities at dedicated CalVal stations.

We reported previously that poly (3-hydroxybutyrate) (PHB) oligomer is an effective antimicrobial agent against gram-positive bacteria, gram-negative bacteria, fungi and multi-drug resistant bacteria. In this work, it was further found that polyethylene glycol (PEG) can promote the antimicrobial effect of PHB oligomer synergistically. Three hypothetic mechanisms were proposed, that is, generation of new antimicrobial components, degradation of PHB macromolecules and dissolution/dispersion of PHB oligomer by PEG. With a series of systematic experiments and characterizations of HPLC-MS, it was deducted that dissolution/dispersion of PHB oligomer dominated the synergistic antimicrobial effect between PHB oligomer and PEG. This work demonstrates a way for promoting antimicrobial effect of PHB oligomer and other antimicrobial agents through improving hydrophilicity.

A novel effective vibrational mode was discovered in the conventional transducer with an array of orthogonal (square) regular piezoelectric rods in 1-3 piezocomposite, containing the damping backing and front matching layers. The operational resonance in the structure was determined as the Surface Acoustic Wave (SAW) on the backing boundary excited by the adjacent piezo-rods, with its frequency typically near 3 times lower the fundamental half-lambda conventional piezocomposite resonance. Pulse-echo sensitivity and transmitting sound-pressure-level (SPL) in air showed that the signal strength is roughly comparable to the industrial similar air transducers at the frequency range 100…700 kHz, where at these frequencies the lateral and longitudinal piezoelement dimensions in the conventional transducer design are typically close to each other causing interference with unwanted coupling modes. As was determined theoretically and proved in experiments, the backing SAW resonance effect in the transducer performance is inherent just to the regular periodic 1-3 piezocomposite structure, and does occur neither with randomly located/oriented piezo-rods, nor in the homogeneous piezo-plate at least with the same lateral cross-section as the connected to it backing. The purpose of the article is to investigate a newly discovered operational vibrational mode of a SAW type in 1-3 regular piezocomposite, other than piezoelectric resonance. The investigated phenomena can improve the transceiver sensitivity, bandwidth, providing lower drive voltage, and smaller and lighter weight ultrasonic transducers. Based on the piezocomposites with thickness’ 1…1.5 mm (rod resonance near 2…3 MHz), pillar width 0.2…0.8 mm, kerf width 0.1…0.4 mm, the transceivers with an operating frequency from 140 kHz to 650 kHz were designed and fabricated with a conventional backing of a mixture of high-density tungsten powder and epoxy, and a matching layer of a mixture of low-density glass bubbles and epoxy. Experimental evaluation of their acoustical performance showed expected characteristics suitable for practical applications.

The taxonomy of trilobites Abadiella Hupé, 1953 and Parabadiella Zhang, 1966 from the lower Cambrian of Gondwana has long been a controversy. Based on newly-collected and formerly-reported materials, 94 trilobite cranidia within 21 species are selected for morphometric analyses: principal components analysis (PCA) and canonical variates analysis (CVA). The integrated morphological characters are successfully accounted for by two principal components in PCA. The further validations for the presupposed qualitative groupings are indispensable to detect and calibrate the ultimate taxonomic results in CVA. By this way, all specimens distributed in a consistent morphospace in PCA and the short distances between them demonstrate their close morphological affinity, supporting their congeneric status within Abadiella. Additionally, three morphotypes were recognized from all selected specimens and they were eventually revised and incorporated into A. bourgini Hupé, 1953, A. huoi Zhang, 1966, and A. yunnanensis Luo, 1981, through stepwise test-calibration to get a high correct rate as far as possible in CVA. From this, it is certain that A. huoi is conspecific in South Australia and South China. Its occurrence allows to correlate the Australian A. huoi Range Zone to the identical zone in South China (in platform), having an approximately consistent stratigraphic range in the two regions. In comparison with A. huoi, A. bourgini was reported from fewer localities in South China. Nevertheless, its presence in the Daguinaspis Zone of Issendalenian Stage in Morocco permits a correlation with Chinese and Australian A. huoi Zone. As an auxiliary marker for A. huoi, the occurrence of A. bourgini in Morocco, South Australia and South China reinforce the correlation potential and resolution in species-level for the Cambrian Stage 3 in Gondwana region.

Despite the publication in 2009 of a paper on ‘terms and definitions of immune thrombocytopenia’, (ITP) some unresolved issues remain and are reflected by the disagreement in the treatment suggested for primary ITP in adults. Considering that these disagreements could be ascribed to non-shared goals, a ‘consensus’ to classify the different lines of treatment for primary ITP in adults according to their indications and goals was proposed in October 2018 to the XIX annual meeting of the Italian Gruppo di Studio delle Piastrine (GSP), a non-profit platelet study group of scientists and physicians. Having approved the project, 60 potential co-authors and experts in the world were invited to take part to a consensus through e-Delphy method and nine of the 12 who initially accepted the invitation completed the work. Agreement was reached on a classification of four lines of treatment for primary ITP in adults based on their indications and goals. The consensus obtained regarded also the criteria, ‘timing’ included, to consider practicable elective splenectomy in these patients. In our opinion, the classification of the lines of treatment for primary ITP in adults here proposed could facilitate the realization of better shared evidence-based guidelines for the treatment of the disease.

In this manuscript we report new effects of resonance detuning on various dynamical parameters of a generic 3-wave system. Namely, for suitably chosen values of detuning the variation range of amplitudes can be significantly wider than for exact resonance. Moreover, the range of energy variation is not symmetric with respect to the sign of the detuning. Finally, the period of the energy oscillation exhibits non-monotonic dependency on the magnitude of detuning. These results have important theoretical implications where nonlinear resonance analysis is involved, such as geophysics, plasma physics, fluid dynamics. Numerous practical applications are envisageable e.g. in energy harvesting systems.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids like total cholesterol (TCH), LDL- and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. This study aimed to investigate the relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities and erythrocyte membrane fluidity in 58 depressive children and adolescents, as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. We are the first to report that omega-3 FAs increase after 12 weeks of supplementation large HDL subfractions (anti-atherogenic) and decrease small HDL subfractions (pro-atherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder.

Kinetic modeling is an essential tool in systems biology research, enabling the quantitative analysis of biological systems and predicting their behavior. However, the development of kinetic models is a complex and time-consuming process. In this article, we propose a novel approach called KinModGPT, which generates kinetic models directly from natural language text. KinModGPT employs GPT-3 as a natural language interpreter and Tellurium as an SBML generator. We demonstrate the effectiveness of KinModGPT in creating SBML models from complex natural language descriptions of biochemical reactions. KinModGPT successfully generates valid SBML models from a range of natural language model descriptions of metabolic pathways, protein-protein interaction networks, and heat shock response. This article demonstrates the potential of KinModGPT in kinetic modeling automation.

In this paper, we present an extended version of the Hadi-Vencheh model for multiple criteria ABC inventory classification. The proposed model is a nonlinear weighted product model (WPM) which determines a common set of weights for all the items. Our proposed nonlinear WPM incorporates multiple criteria with different measure units, without converting the performance of each inventory item in terms of each criterion into a normalized attribute value, thereby providing an improvement over the model proposed by Hadi-Vencheh. Our study mainly includes various criteria for ABC classification, and demonstrates an efficient algorithm for solving nonlinear programming problems in which the feasible solution set does not have to be convex. The algorithm presented in this study improves the solution efficiency of the Canonical Coordinates Method (CCM) algorithm substantially when applied to large scale, nonlinear programming problems. The modified algorithm was tested to compare our proposed model results to the results derived using the Hadi-Vencheh model and demonstrate the algorithm's efficacy. The practical implications of the study are to develop an efficient nonlinear optimization solver by optimizing the quality of existing solutions, thus improving time and space efficiency.

In the energy-momentum density expressions for a relativistic perfect fluid with a bulk motion, one comes across a couple of pressure-dependent terms, which though well known, are to an extent, lacking in their conceptual basis and the ensuing physical interpretation. In the expression for the energy density, the rest mass density along with the kinetic energy density of the fluid constituents due to their random motion, which contributes to the pressure as well, are already included. However, in a fluid with a bulk motion, there are, in addition, a couple of explicit, pressure-dependent terms in the energy-momentum densities, whose presence to an extent, is shrouded in mystery, especially from a physical perspective. We show here that one such pressure-dependent term appearing in the energy density, represents the work done by the fluid pressure against the Lorentz contraction during transition from the rest frame of the fluid to another frame in which the fluid has a bulk motion. This applies equally to the electromagnetic energy density of electrically charged systems in motion and explains in a natural manner an apparently paradoxical result that the field energy of a charged capacitor system decreases with an increase in the system velocity. The momentum density includes another pressure-dependent term, that represents an energy flow across the system, due to the opposite signs of work being done by pressure on two opposite sides of the moving fluid. From Maxwell's stress tensor we demonstrate that in the expression for electromagnetic momentum of an electric charged particle, it is the presence of a similar pressure term, arising from electrical self-repulsion forces in the charged sphere, that yields a natural explanation for the famous, more than a century old, 4/3 factor in the electromagnetic mass.

Rationale: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. Objective: To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs. Methods and Results: We evaluated both RNA expression and protein abundance of 14-3-3 isoforms in mouse heart, followed by co-immunoprecipitation of 14-3-3 proteins and mass spectrometry in left ventricle. We identified 52 proteins comprising the cardiac 14-3-3 interactome. Multiple bioinformatic analyses indicated that more than half of the proteins bound to 14-3-3 are related to mitochondria; and the deduced functions of the mitochondrial 14-3-3 network are to regulate cardiac ATP production via interactions with mitochondrial inner membrane proteins, especially those in mitochondrial complex I. Binding to ribosomal proteins, 14-3-3 proteins likely coordinate protein synthesis and protein quality control. Localizations of 14-3-3 proteins to mitochondria and ribosome were validated via immunofluorescence assays. The deduced function of cardiac 14-3-3 PPIs is to regulate cardiac metabolic homeostasis and proteostasis. Conclusions: Thus, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.

The collision avoidance mechanism adopted by the IEEE 802.11 standard is not optimal. The mechanism employs a binary exponential backoff (BEB) algorithm in the medium access control (MAC) layer. Such an algorithm increases the backoff interval whenever a collision is detected to minimize the probability of subsequent collisions. However, the expansion of the backoff interval causes degradation of the radio spectrum utilization (i.e., bandwidth wastage). That problem worsens when the network has to manage the channel access to a dense number of stations, leading to a dramatic decrease in network performance. Furthermore, a wrong backoff setting increases the probability of collisions such that the stations experience numerous collisions before achieving the optimal backoff value. Therefore, to mitigate bandwidth wastage and, consequently, maximize the network performance, this work proposes using reinforcement learning (RL) algorithms, namely Deep Q Learning (DQN) and Deep Deterministic Policy Gradient (DDPG), to tackle such an optimization problem. As for the simulations, the NS-3 network simulator is used along with a toolkit known as NS3-gym, which integrates a reinforcement-learning (RL) framework into NS-3. The results demonstrate that DQN and DDPG have much better performance than BEB for static and dynamic scenarios, regardless of the number of stations. Moreover, the performance difference is amplified as the number of stations increases, with DQN and DDPG showing a 27% increase in throughput with 50 stations compared to BEB. Furthermore, DQN and DDPG presented similar performances.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

The disruptive application of ChatGPT (GPT-3.5, GPT-4) to a variety of domains has become a topic of much discussion in the scientific community and society at large. Large Language Models (LLMs), e.g., BERT, Bard, Generative Pre-trained Transformers (GPTs), LLaMA, etc., have the ability to take instructions, or prompts, from users and generate answers and solutions based on very large volumes of text-based training data. This paper assesses the impact and potential impact of ChatGPT on the field of digital forensics, specifically looking at its latest pre-trained LLM, GPT-4. A series of experiments are conducted to assess its capability across several digital forensic use cases including artefact understanding, evidence searching, code generation, anomaly detection, incident response, and education. Across these topics, its strengths and risks are outlined and a number of general conclusions are drawn. Overall this paper concludes that while there are some potential low-risk applications of ChatGPT within digital forensics, many are either unsuitable at present, since the evidence would need to be uploaded to the service, or they require sufficient knowledge of the topic being asked of the tool to identify incorrect assumptions, inaccuracies, and mistakes. However, to an appropriately knowledgeable user, it could act as a useful supporting tool in some circumstances.

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

The traditional nomenclature system for classifying Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), based on clinical phenotype, described Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and every day clinical practice, yet, a substantial overlap in clinical presentation still exists, and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative), could be more accurate and also closer to the nature of the disease, instead of the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV, in terms of epidemiology, pathogenesis, histological and clinical manifestations, and response to therapeutic approaches.

Chat generative pre-trained transformer (ChatGPT) is a developed language model and a subgroup of artificial intelligence (AI) which has demonstrated noticeable innovation in interactions between computer models and human studies. The release of ChatGPT in November 2022 attracted over 100 million users in a short time. It has unlimited applications in different fields of studies such as technology and science. ChatGPT utilizes deep learning and internet text to produce responses that resemble human language, although their accuracy is not always guaranteed. ChatGPT and GPT-4 can make a huge revolution in biology, medical, dental research, and health care. However, it's important to acknowledge the limitations of ChatGPT such as limitation in accessing the latest data. ChatGPT has generated both excitement and concern regarding its potential misuse. Its utilization in scientific publications has sparked debates and prompted the development of policies to govern the use of it. Although ChatGPT has certain limitations, it could impact on many different fields of study. There are challenges associated with using ChatGPT in the field of laboratory medicine and biology, particularly in the interpretation of test results. In this article, we review some of the applications of ChatGPT and GPT-4 in biology, dental and medical studies, and concerns about ChatGPT. Despite ChatGPT's conversational abilities are impressive, there are important considerations regarding its use in different fields of research and academic public.

We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGF stimulated global fibrin matrix contraction (P < 0.005), however cell and matrix patterning were different. We found that during PDGF BB induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (P < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (P < 0.001). Taken together, our results show that cell-induced ECM reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

According to the risk investigations of being involved in an accident, alcohol-impaired driving is one of the major causes of motor-vehicles accidents. Preventing highly intoxicated persons from driving would potentially save many lives. This paper proposes a lightweight in-vehicle alcohol detection that processes the data generated from 6-alcohol sensors (MQ-3 Alcohol Sensors) using an optimizable shallow neural network (O-SNN). The experimental evaluation results exhibit a high-performance detection system scoring a 99.8% of detection accuracy with a very short inferencing delay of 2.22 µ seconds. Hence, the proposed model can be efficiently deployed and used to discover in-vehicle alcohol with high accuracy and low inference overhead as a part of the driver alcohol detection system for safety (DADSS) system aiming at massive deployment of alcohol sensing systems that could potentially save thousands of lives annually.

This study aimed to use remote sensing and GIS to detect changes in surface water and wetlands in the Kumasi Metropolis over a period of 20 years (2002-2022). Landsat images were processed using the QGIS software, and the Maximum Likelihood Algorithm was used to perform supervised classification of land use land cover, while raster calculator aided in detecting wetlands by calculation for NDWI, MNDWI, and AWEI. The results showed that the majority of the landscape in the Kumasi metropolis was made up of built-up areas (79.4%), followed by agricultural lands (13.3%) and wetlands (7.3%). Over the 20-year period, built-up areas had gained 20.7% of the total landscape, while agricultural lands and wetlands had lost 16.7% and 4.0%, respectively. All water index methods recorded an increase in non-water cover and a loss of water cover over the period, with surface water decreasing by 5% and non-water land cover increasing by 5%. The study concludes that there have been significant changes in wetlands and surface water land use and land cover within the Kumasi Metropolis over the past 20 years, and recommends the enforcement of legislation on surface water protection in the area to protect wetlands

The KRAS mutant population has been undruggable for 40 years. G12C inhibitors and immunotherapy are the beginning of success. It is necessary to summarize the successful experience of the existing treatment model and explore the direction of the next treatment. In this review, we discuss the latest developments in targeted therapy and immunotherapy for KRAS-mutation NSCLC, aiming to provide direction or enlightenment for future treatment strategies.

The physicalchemistry properties and crystal structure of were nano-ZrO₂+3mol.%Y₂O₃ determined. The kinetics of the formation of H₂ as a result of the decomposition of H₂O on the surface of nano-ZrO₂+3mol.%Y₂O₃ was studied. Effects of adsorption and desorption process on ZrO₂+3 mol.%Y₂O₃ nanoparticles were studied at different (T=400÷1000⁰C) temperature. The study of H₂ in thermal processes at nano-ZrO₂+3 mol.%Y₂O₃ system increased. Such an increase in H₂ generation in comparison with a pure H₂O as thermal processes had formedactive centers for H₂O decomposition on the surface of the catalyst at the expense of δ-electrons emitted on the surface of nano-ZrO₂+3 mol.%Y₂O₃. This showed that the dimensions of the studied nanoscale particles systems are comparable to the free running distance of energy carriers generated by of nano-ZrO₂+3 mol.%Y₂O₃ as a result of thermal processes. These results are promising for hydrogen generation by waer spliting in near future.

Gene expression variations of plant leaf are investigated by irradiating seed and leaf with oxygen or air plasmas. Enhancement of leaf growth is induced by oxygen plasma irradiation on seeds, which is supported by increased gene expression for protein synthesis, oxidative-reduction reactions and decreased gene expression concerning DNA methylation and histone modification. Suppression of leaf growth is observed by the oxygen plasma, which would be owing to increased gene expression concerning heat shock protein and redox reaction, and decreased expression of photosynthesis and glycoprotein. Also, gene expression variation due to air plasma irradiation is almost same as that of oxygen plasma. Active oxygen species are major factors in both oxygen and air plasmas for the variation of gene expressions in plant.

In spite of its incidence on pistachio trees, the chemical ecology of Labidostomis lusitanica (Germar) (Coleoptera: Chrysomelidae) has been neglected so far. In this work we provide the first evidence of a biologically active male-specific compound that may be promoting field aggregation. Headspace collections by solid-phase microextraction from feral males and females reported the presence of 2-isobutyl-3-methoxypyrazine exclusively on males. Electroantennographic recordings revealed that males and females responded in a dose-dependent manner to increasing stimuli of 2-isobutyl-3-methoxypyrazine, with females overall displaying a higher response than males. In dual-choice tests, both males and females showed a significant preference for the compound in comparison to a pure air stimulus. In the light of these results, the possible role of 2-isobutyl-3-methoxypyrazine as an aggregation cue in L. lusitanica is discussed.

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered as one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones. The probability of cytoprotective action was assessed by two tests by measuring cell viability (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones under the conditions of our experiment have a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones also fully satisfy Lipinski's rule of thumb of five (RO5), which increases their chances for possible use as orally active drugs with a good ability to absorption and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones as having a relatively high cytoprotective potential.

Footprints are powerful indicators for evaluating the impact of the bioeconomy of a country on environmental goods, domestically and abroad. In this study, we apply a hybrid approach combining a Multi-Regional Input-Output model and land use modelling to compute the agricultural land footprint (aLF). Furthermore, we added information on land-use change to the analysis and allocated land conversion to specific commodities. The German case study shows that the aLF abroad is larger by a factor of 2.5 to 3 than the aLF in Germany. In 2005 and 2010, conversion of natural and semi-natural land-cover types abroad allocated to Germany due to import increases was 2.5 times higher than the global average. Import increases to Germany slowed down in 2015 and 2020, reducing land conversion attributed to the German bioeconomy to the global average. The case study shows that the applied land footprint provides clear and meaningful information for policymakers and other stakeholders. The presented methodological approach can be applied to other countries and regions covered in the underlying database EXIOBASE. It can be adapted, also for an assessment of other ecosystem functions, such as water or soil fertility.

Cesium lead iodide (CsPbI3) perovskite nanocrystals (NCs) are a promising material for red light-emitting diodes (LEDs) due to their excellent color-purity and high luminous efficiency. However, small-sized CsPbI3 colloidal NCs, such as nanocubes, used in LEDs suffer from confinement effects, negatively impacting their photoluminescence quantum yield (PLQY) and overall efficiency. Here, we introduced YCl3 into the CsPbI3 perovskite, which formed anisotropic, one-dimensional (1D) nanorods. This was achieved by taking advantage of the difference in bond energies between Cl− and I− ions, which caused YCl3 to promote the anisotropic growth of CsPbI3 NCs. The YCl3-based nanorods improved the PLQY and storage stability by passivating the defects reducing the nonradiative recombination rates. When the YCl3-substituted CsPbI3 nanorods are applied to the emissive layer in LEDs, we achieve an external quantum efficiency of ~3.16% which is 1.86-fold higher than the pristine CsPbI3 NCs (1.69%) based LED. Notably, the ratio of horizontal transition dipole moments (TDMs) in the anisotropic YCl3:CsPbI3 nanorods was determined to be 75%, which is higher than the isotropically oriented TDMs in CsPbI3 nanocrystals (67%). This increased TDM ratio led to higher light outcoupling efficiency in nanorods-based LEDs. Overall, the results suggest that YCl3-substituted CsPbI3 nanorods could be promising for achieving high-performance perovskite LEDs.

The rapid progress in artificial intelligence, machine learning, and natural language processing has led to the emergence of increasingly sophisticated large language models (LLMs) enabling their use in healthcare. The study assesses the performance of two LLMs: the GPT-3.5 and GPT-4 models in passing the medical examination for access to medical specialist training in Spain MIR. Our objectives included gauging the model's overall performance, analyzing discrepancies across different medical specialties, discerning between theoretical and practical questions, estimating error proportions, and assessing the hypothetical severity of errors committed by a physician. We studied the 2022 Spanish MIR examination after excluding those questions requiring image evaluations or having acknowledged errors. The remaining 182 questions were presented to the LLM ChatGPT4 and GPT-3.5 in Spanish and English. Logistic regression models analyzed the relationships between question length and question sequence d performance. GPT-4 outperformed GPT -3.5, scoring 86.81% in Spanish (p<0.001). English translations had a slightly enhanced performance. Among medical specialties, GPT-4 achieved a 100% correct response rate in several areas, with specialties like Pharmacology, ICU, and Infectious Diseases showing lower performance. The error analysis revealed that while a 13.2% error rate existed, gravest categories like "error requiring intervention to sustain life" and "error resulting in death" had a 0% rate. Conclusions: GPT-4 performs robustly on the Spanish MIR examination, varying its capability to discriminate knoweldge across specialties. While the model's high success rate is commendable, understanding the error severity is critical, especially when considering AI's potential role in real-world medical practice and its implication on patient safety.

Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity that in turn determines the tumor cell response towards therapeutic drugs. Sever-al lines of evidence suggest that therapeutic interventions foster the selection of drug resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melano-ma. Here we established a dual reporter system enabling the tracking of NGFR expression and mRNA stability, providing insights into the maintenance of NCSC-states. We observed that the transcriptional reporter that contained a 1kb fragment of the human NGFR promoter was acti-vated only in a minor subset (0.72±0.49%, range 0.3-1.5) and ~2-4% of A375 melanoma cells re-vealed stable NGFR mRNA. The combination of both reporters provided insights into pheno-type switching and revealed that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated genes serving as potential drivers of a NGFR-associated phenotype switching in vitro and in relapsed, post-BRAF inhibitor treated tu-mors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provided insights into plastici-ty and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

In this paper, we introduce an innovative approach to distinguish Gliosarcoma (GSM) from Glioblastoma (GBM). Our method combines causal fuzzy logic rules with the Big Bird architecture, a Transformer-based Deep Learning algorithm. Unlike prior research, which often relied on statistical models to reduce dataset dimensions before causal analysis, our approach harnesses the complete dataset in tandem with our causal fuzzy Big Bird architecture. Additionally, we benchmark our results not only against previous Gliosarcoma/Glioblastoma studies but also against GPT-2 for a comprehensive evaluation.

The antibodies targeting invasive proteins of Plasmodium falciparum (Pf) merozoites is a clever strategy against malaria parasite. The recent finding that Plasmodium merozoites surface enolase is a target for growth neutralizing antibodies has generated interest in identifying its re-ceptor (s) on erythrocytes. In the present study, several biochemical experiments were undertaken involving recombinant Pf enolase and antibody against it to search for its cognate receptor. The binding of rPfeno to erythrocytes was selectively sensitive to trypsin but resistant to neuramini-dase. Failure of yeast enolase binding to human red blood cells under similar conditions indicat-ed high specificity of parasite Pfeno. The mass spectrometric and immunological analyses of pro-teins obtained in pull downs and co-immunoprecipitation samples led to identification of band 3 as an interactor/receptor for Plasmodium enolase. Structural characterization of sequences of band 3 - rPfeno interacting regions revealed C-terminal exocytic regions of band 3 to be binding to Pfeno. Similarly, band 3 binding regions of rPfeno were also identified. Identification of receptor-ligand (band 3: Pfeno) pair paves the way for antimalarial anti-Pf enolase-based vaccine, anti-Pf enolase antibodies as drug and also for developing novel small molecule-based invasion inhibi-tory therapeutics including peptidomimetics that could disrupt the band 3: Pfeno protein-protein interactions.

This paper proposes the utilization of large language models as recommendations systems for museums. Since the aforementioned models lack the notion of context, they can’t work with temporal information that is often present in recommendations for cultural environments (e.g. special exhibitions or events). In this respect, the current work aims at enhancing the capabilities of large language models through a fine-tuning process that incorporates contextual information and user instructions. The resulting models are expected to be capable of providing personalized recommendations, aligned with user preferences and desires. More specifically, Generative Pre-trained Transformer 4, a knowledge-based large language model is fine-tuned and turned into a context-ware recommendation system, adapting its suggestions based on user input and specific contextual factors such as location, time of visit, and other relevant parameters. The effectiveness of the proposed approach is evaluated through certain user studies, which ensure an improved user experience and engagement within the museum environment.

This paper presents a proposal for a non-isolated bidirectional converter (NIBC) controlled by a deep neural network (DNN) to enable vehicle-to-vehicle (V2V) and vehicle-to-grid (V2G) charging, which contributes to the development of more efficient and sustainable transportation and energy systems. The DNN controller manages power flow in both directions, making it possible to charge electric vehicles (EVs) and discharge power from EVs to the grid with improved efficiency and performance compared to traditional control methods. The non-isolated topology used in this proposal offers several benefits, including reduced cost, smaller size, and higher efficiency. To train the DNN controller, a large dataset of simulations was used, and the results were validated with a hardware setup. The real-time performance of the DNN controller was compared to a proportional-integral (PI) based controller through simulated results. The findings of the study show that the DNN controller outperforms traditional PI controllers.

Forests, integral to human civilization, hold immense value and play a vital role in maintaining ecological harmony. Despite India's goal of extensive forest coverage, significant progress is still needed. Uncontrolled forest fires pose a severe threat, particularly in Uttarakhand's Pauri Garhwal district. To address this challenge, a comprehensive study examined surface and subsurface hydrological factors influencing the forest fire occurrences, such as elevation, aspect, slope, vegetation, proximity to human settlements, proximity to waterbodies, Active faults and lineament density. A total of 15 such factors were integrated with advanced techniques of remote sensing and GIS and coupled with historical fire data to create a precise forest fire risk map using the support vector machine algorithm. Forest fire risk map was classified into 5 distinct risk zones, Very High Risk (47.38 Km2), High Risk (275.98 km2, Moderate Risk (985.49 km2), Low Risk (1741.17 km2) and Very Low Risk (2374.11 km2) aiding in proactive fire management. By embracing this innovative tool, decision-makers can protect forests, preserve biodiversity, and ensure a sustainable future for generations to come.

Although conventional chemotherapeutic drugs are the first line of treatment for cancer, they have numerous side effects. One of the emerging challenges in cancer treatment is drug resistance. Nat-ural compounds have proven effective against various hallmarks of cancer for their multi-target inhibition properties, but especially for their ability to synergistically bypass low bioavailability. Methods: The present study investigated the in vivo antitumor effects of a combination of two natural dietary agents, epigallocatechin-3-gallate (EGCG) from Camelia Sinensis and curcumin, a component of turmeric (Curcuma longa). We aimed to compare, for the first time in vivo, the antiangiogenic and antitumor effects of sunitinib with the combination of curcumin and EGCG in a mouse model of renal cell carcinoma (ccRCC). It was shown that they are able to inhibit cell survival, proliferation of several type of cancer, including renal cell carcinoma (ccRCC), by mod-ulating different signaling pathways and that their combination respect to single compound syn-ergistically decreased angiogenesis. Results: Herein, we highlighted that these compounds inhib-ited the growth of xenografted renal cancer in nude mice by significant inhibition of tumor vol-ume, tumor weight and CD31 expression with no signs of hepatic toxicity. Moreover, mice treated with these natural compounds showed a significant reduction in angiogenesis and an improve-ment in survival rate with p<0.05. Finally, pretreatment of mice with a diet containing 0.6% curcumin before injection of tumor cells showed a significant inhibition of tumor engraftment in 60% of mice with respect to controls and other groups. Conclusions: Taken together, our data in-dicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of re-nal cancer.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

Modification of the brainstorming process by the application of artificial intelligence (AI) is proposed. System design of the software tool “kresilnik” is provided, which enables hybrid work of the human group and AI. The proposed system integrates OpenAI-GPT-3.5-turbo model with the server side providing the results to clients. The proposed architecture provides the possibility to not only generate ideas but also categorize them and set priorities. With the developed prototype, 760 ideas were generated on the topic of the design of the Gorenjska region development plan at eight different values of OpenAI-GPT-3.5-turbo algorithm temperatures. For the set of generated ideas, the entropy was determined, as well as the time needed for generation. Entropy distributions of the human group as well as AI-generated sets of ideas at different OpenAI-GPT-3.5-turbo algorithm temperatures, are provided in the form of histograms. Ideas were presented as a word cloud for one human group and AI-generated sets. A comparison of the idea-generation process between the human group and AI was conducted. The statistical Mann-Whitney U-test was performed, which confirmed the significant differences in the average entropy of generated ideas. Correlations between the length of the generated ideas and the time needed were determined for the human group and AI. Distributions for needed times and length of the ideas were determined, which are possible indicators to distinguish between human and artificial idea generation processes.

Today's major challenge for smart Microgrids is to ensure the security of communications in a large number of changing data sets that are vulnerable to attacks by denial of services in constant evolution. The Internet Protocol Traceback defines a set of methods that help identify the source of an attack with minimal requirements for memory and processing. However, the concept of Traceback is not yet being used in smart Microgrids. As a result, the main challenge of this article is to incorporate a new Traceback approach into the cybernetic system of a smart mesh Microgrid, which can be tested using a network simulator (NS-3) based on delay, debit, and packet loss rate parameters. In fact, the simulation results show the efficacy of this approach compared to others existing in the literature. Furthermore, using the proposed Traceback technique and the mesh nodes, we were able to create a smart meshed Microgrid. Moreover, using the Traceback approach given for merging Intel Galileo Gen.1 nodes with the Compex WLE200NX.11a/b/g/n to establish a secure test bench, which is deployed as a prototype at the Sfax Digital Research Center in Tunisia, we were able to create an intelligent Microgrid. In fact, by identifying all attack vectors and revealing their origins, we could boost the efficiency of our operation by 100%.

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

Since the release of ChatGPT, numerous studies have highlighted the remarkable performance of ChatGPT, which often rivals or even surpasses human capabilities in various tasks and domains. However, this paper presents a contrasting perspective by demonstrating an instance where human performance excels in typical tasks suited for ChatGPT, specifically in the domain of computer programming. We utilize the IEEExtreme Challenge competition as a benchmark — a prestigious, annual international programming contest encompassing a wide range of problems with different complexities. To conduct a thorough evaluation, we selected and executed a diverse set of 102 challenges, drawn from five distinct IEEExtreme editions, using three major programming languages: Python, Java, and C++. Our empirical analysis provides evidence that contrary to popular belief, human programmers maintain a competitive edge over ChatGPT in certain aspects of problem-solving within the programming context. In fact, we found that the average score obtained by ChatGPT on the set of IEEExtreme programming problems is 3.9 to 5.8 times lower than the average human score, depending on the programming language. This paper elaborates on these findings, offering critical insights into the limitations and potential areas of improvement for AI-based language models like ChatGPT.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFA) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFA regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFA. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA. However, several are under development, and the FDA anticipates their fast entry, as evidenced by the FDA's actions of issuing GE-specific guidelines. The potential of GE in treating diseases far supersedes any other modality due to the recognized role of genes in most human diseases. While GT products add missing genes, GE tools can overcome many aberrations. However, GE presents many safety challenges, including off-target impact, delivery consistency, and long-term effects of gene-fixing. However, most of these concerns will be resolved once the FDA begins approving them, leading to hundreds of products capable of treating untreatable diseases.

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.

Among cross-sectional imaging modalities, computed tomography (CT) is more available and faster; however, magnetic resonance (MR) performs better in terms of sensitivity and specificity, due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR depends mainly on the primary tumour histology: in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights on the tumour origin. The time-point of tumour evolution, previous or ongoing treatments and the peritoneal spaces where they occur, also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is mandatory in detection and characterization of peritoneal deposits. Several benign and malignant conditions may show similar imaging features that overlap those of PC, making the differential diagnosis challenging. Clinical history, laboratory findings and previous imaging examinations must be considered to achieve the correct diagnosis.

The Surface Urban Heat Island (UHI) is caused by the difference in temperature between the urban and its surrounding areas. However, in the scientific literature, there is no solid methodology defining urban and non-urban areas, which is essential to estimate the SUHI with greater accuracy. This study uses the official national urban areas limit, to obtain the SUHI more accurately on the nine northeastern Brazilian capitals. The land surface temperature was obtained using the Sentinel 3 satellite data for the years 2019 and 2020. Afterward, the maximum and average SUHI, and the complementary indexes were calculated, such as the Urban Thermal Field Variation Index (UTFVI) and the Thermal Discomfort Index (TDI) for the urban areas and their surrounding areas. The Maximum and Average SUHI, obtained values between 1.85 and 8.25 and -4.92 and 2.59 degree difference, respectively, proving the SUHI existence in the study areas. The UTFVI, with values between 0.010 and 0.040, expresses how bad the eco-environmental spaces of urban are. The TDI, with values between 24.61 and 28.89 ºC, expresses the population’s thermal comfort. Therefore, this study provides a better understanding of the surface UHI pioneeringly for the Brazilian Northeast Region.

Air pollution has been a major environmental issue worldwide from the last few decades. It is a man-made issue that has a serious harmful impact on the environment and the health of humans. There are different sources of emission, but industrial processes and motor vehicles contribute to a chief part of air pollution. It has acute as well as chronic effects on the health of humans and affects different organs. It is thought the main environmental risk factor in the incidence and progression of several diseases such as lung cancer, asthma, Alzheimer's and Parkinson's diseases. Long-term exposure to air pollution has different toxicological impacts on humans such as respiratory and cardiovascular diseases, neuropsychiatric complications, eye irritation and skin diseases. As per the study by the World Health Organization (WHO), nitrogen oxides (NOx), carbon monoxide (CO), ozone (O₃), sulfur dioxide (SO₂), volatile organic compounds (VOCs) and heavy metals are the major air contaminants. These pollutants are different in their properties, composition and time of disintegration. The aim of this study is to review the different sources, types, impacts, challenges and mitigation of air pollution in detail.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

Additionally, the League’s four observing states, with an additional population of 1.7 billion, if join the group, will form the world’s largest consortium to enhance the accessibility of biotechnology drugs. This effort will also remove the criticism of regulatory agencies that are well-equipped to regulate these products. This should also be a significant economic incentive to consortium states to develop these products, particularly biosimilars, to capture the most critical market anticipated. This plan will also reduce the cost burden on regulatory agencies. The program is divided into two classifications; for products sold in any of the Stringent Regulatory Authority (SRA) states, the registration is automatic but with several requirements that assure ongoing pharmacovigilance; this also applies to copies of reference products or biosimilars. For non-SRA sourcing, a stepwise plan requiring a rapporteur review, as practiced by the EMA and a third-party cGMP audit, is necessary to ensure data and product integrity. However, to reduce the cost burden, approval of these products is based on current scientific findings as presented in this paper.

Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDD), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM’s effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediate inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1 and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells resulted to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDD.

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

The altimeter-derived ocean currents have been sparsely evaluated against in situ measurements in the Arctic, particularly for extended time periods. This study uses the extensive mooring array situated in the Fram Strait, representing one of the longest ocean current records, to investigate the relationship between in situ and satellite-derived currents in the region. The primary objective of this research is to analyze the vertical structure of the West Spitsbergen Current (WSC), its spatio-temporal coherence, and its association with surface geostrophic currents during the period of 1997-2012. To assess the vertical structure of the WSC, we utilized the Empirical Orthogonal Functions (EOF) and cross-correlation analysis between neighboring moorings. Remarkably, both velocity components exhibited robust vertical coherence, particularly within the waters of the North Atlantic Inflow, at depths exceeding 800 m. These findings underscore the potential for surface measurements to effectively complement data gaps and facilitate the reconstruction of deeper currents with a monthly temporal resolution. Notably, the surface measurements explain approximately 67% of the variance in the top 800 m of the water column.This comprehensive investigation advances our understanding of the West Spitsbergen Current and its vertical characteristics in the Arctic. Moreover, our findings highlight the valuable synergy between in situ and satellite-derived data, providing critical insights for future ocean current studies in this ecologically sensitive region.

The aim of this study was to determine the microbial stability, challenge to L. monocytogenes, and some physicochemical properties of turkey breast meat by alginate-based coating enriched with postbiotics (8% concentration, CFS) of Bifidobacterium bifidum DSM 20456 and Bifidobacterium bifidum BB12 strains. For this purpose, firstly, some antimicrobial and total phenolic matter, flavonoid, and DPPH activity values of postbiotics were determined. In addition, FTIR analysis was performed to see the intermolecular interactions of the biological coating agent. As a result of the study, alginate solution with postbiotic showed significant differences in pH, a*, b*, yeast-mold values of turkey meat during storage (7 days), while L* value, total aerobic mesophilic bacteria count (TMAP), psychrotrophic bacteria (PAB), lactic acid bacteria (LAB) and Listeria monocytogenes count were not effective (p&gt;0.05).

Open-source 3-D printing has played a pivotal role in revolutionizing the additive manufacturing (AM) landscape, by making distributed manufacturing economic, democratizing access, and fostering far more rapid innovation than antiquated proprietary systems. Unfortunately, some 3-D printing manufacturing companies began deviating from open-source principles and violating licenses for the detriment of the community. To determine if a pattern has emerged of companies patenting clearly open-source innovations, this study presents three case studies from the three primary regions of open-source 3-D printing development (EU, U.S. and China) as well as three aspects of 3-D printing technology (AM materials, an open-source 3-D printer, and core open-source 3-D printing concepts used in most 3-D printers). The results of this review have shown that non-inventing entities called patent parasites are patenting open-source inventions already well-established in the open source community and in the most egregious cases commercialized by one (or several) firms at the time of the patent filing. Patent parasites are able to patent open-source innovations by using a different language, vague patent titles and broad claims that encompass enormous swaths of widely diffused open-source innovation space. This practice poses a severe threat to innovation and several approaches to irradicate the threat are discussed.

Porcine parvovirus (PPV) 1 is a major causative pathogen of reproductive failure, and porcine circovirus (PCV) 2 is an etiological pathogen causing PCV-associated and PCV diseases worldwide. PPV2–6 and PCV3 were recently identified as newly emerging viruses with unknown pathogeneses. However, little is known of PPV1–6 and PCV3 effects or their co-infections with PCV2. In this study, we examined 926 samples (272 aborted pig fetuses and 654 pig lung tissues) from domestic pig farms for the presence of PPV1–6 or PCV3 and for PCV2 co-infection with these seven viruses. The prevalence of PPV and PCV was significantly greater in lung tissue samples than aborted pig fetus samples. PPV3–6 were detected for the first time in Korean domestic pigs. Co-infection rates with PCV2 and other viruses were significantly higher in abattoir samples than that in aborted pig fetus samples. Concurrent infections are more common than single infection in pig population and nu-merous infectious pathogens such as PPV and PCV2 can impact the respiratory diseases. Fur-thermore, Korean PPV1 strain (PPV1-82) was identical to the virulent PPV-27a strain in this respect. Our results describe, for the first time the prevalence of PPV1–6 and PCV3 infections and their co-infection rates with PCV2 in Korean domestic pigs.

After a long limbo, RNA has gained its credibility as a druggable target, fully earning its de-served role in the next-generation area of pharmaceutical R&D. We have recently probed the Trans-Activation Response element (TAR), a RNA stem–bulge–loop domain of the HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed the compounds unique behavior in stabiliz-ing TAR structure, thus impairing in vitro the chaperone activity of the HIV-1 nucleocapsid (NC) protein. Seeking to elucidate the determinants of B-CePs inhibition, we have further characterized here their effects on the target TAR and its NC recognition, while developing quantitative analyti-cal approaches for the study of multicomponent RNA-based interactions.

Natural products, especially biologically active compounds derived from plants, have been and continue to be invaluable in anticancer research and therapeutic discoveries. Rice bran arabinoxylan compound (RBAC) is a heteropolysaccharide extract of defatted rice bran obtained through enzymatic treatment with Lentinus Edodes mycelium. RBAC exhibited antitumour properties by arresting in vivo tumour growth in several murine models. In vitro experiments showed RBAC to promote apoptosis in cancer cells by increasing the susceptibility of CD95 (Fas/APO-1) ligands and downregulating Bcl-2 proteins to trigger the permeabilisation of the mitochondrial membrane. RBAC may restore immune dysfunction in cancer patients, most notably by upregulating natural killer cell activity and modulating cytokine production to enhance inflammatory and cytotoxic responses. As such, RBAC acts on the immune system to enhance chemopreventative activity and block tumourigenesis. In treatment, RBAC works synergistically with other natural products and chemotherapeutic agents, such as daunorubicin and paclitaxel, by enhancing drug transport to increase DNA damage in tumours and reduce proliferation. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence, and prolonged survival time. RBAC has been shown to augment the endogenous antioxidant system to prevent oxidative stress and thus protect against the harmful side effects of radiation therapy. RBAC also has chemoprotective effects, with animal and human studies showing reduced toxicity and side effects from chemotherapy, leading to improved health-related quality of life. Meta-analysing the best available evidence indicates that RBAC treatment increases the odds of survival among cancer patients by 4.02 times (95% CI: 1.67, 9.69) in the first year and 2.89 (95% CI: 1.56, 5.35) times in the second year after commencing treatment, compared to those not treated with RBAC. Notwithstanding, additional research is needed to characterise, quantify, and standardise the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to further substantiate the treatment efficacies.

The field of mitochondrial genomics has advanced rapidly and revolutionized disciplines from molecular anthropology, population genetics, to medical/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated, mitogenome database and efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4,286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient and accurate means of sequence analysis for translational mitogenomics.

Galectins have been shown to have roles in cancer progression via contributions to angiogenesis, metastasis, cell division, and evasion of immune destruction. This study analyses galectin-1, -3, and -9 serum concentrations in breast cancer patients by enzyme-linked immunosorbent assay (ELISA) against the characteristics of the patient and tumor such as stage, molecular subtype, and receptor expression. Galectin-9 was found to be statistically significantly increased in HER2 enriched tumors as well as being reduced in patients with hormone receptor positive tumors and increased in patients with HER2 amplified tissues. Galectin-1 was found to be statistically significantly increased in the serum of patients who had undergone hormonal, immunotherapy, or chemotherapy. These findings provide insight as to the changes in galectin levels during cancer progress, response to treatment and molecular phenotype. These findings are valuable in the further understanding of the relationships of galectin and tumor biology and can inform future research on therapeutic targets for galectin inhibitors and the utility of galectin biomarkers.

In an historic perspective on the development of the Standard Model of particle physics it is shown how mathematically driven axioms have masked the merits of a physically comprehensible structural view. It is concluded that the difference between the two approaches can be traced back to two major issues. Whereas in the Standard Model the quark is a Dirac particle with a single real dipole moment, the quark in the structural model, in confinement with other quarks, is a Dirac particle with two real dipole moments. The second issue is the view that empty space does not exist, but that space is filled with a polarisable energetic fluid. It is shown how recognition of these two issues pave a road to reconcile particle physics with gravity, in which the quark can be seen as a magnetic electron and in which the gluon, as the strong force carrier, can be seen as a massive photon.

The hepatitis E virus (HEV) is a zoonotic pathogen with a variety of hosts, including pigs, which act as reservoirs. In industrialized countries, sporadic cases caused by genotype 3, contracted by ingestion of contaminated uncooked or undercooked meat, have been reported. However, in developing countries, HEV infection is mainly dominated by genotype 2 and often associated with poor hygiene conditions and drinking water supplies. In West Africa, HEV infection and its circulation in domestic fauna are very poorly documented. The aim of this study was to assess the presence of HEV in pork sold in Saint-Louis. Meat products were collected between 20 and 25 August 2022 in three location of Saint-Louis region. After purchasing 250 g of sample, we minced 2 g of sample for extraction of total nucleic acids using the Purelink™ Viral DNA/RNA kit and then RT-PCR using the One-Taq™ One-Step RT-PCR kit targeting the HEV ORF2 genomic region. The products obtained were visualized on a 1% agarose gel. Of a total of 74 samples, divided into pork meat (n=65) and pork liver (n=9), 5.4% (n=4) were tested positive for HEV. In both cases, 2 samples were positive, representing a rate of 3.1% and 22.2% for meat and pork liver respectively. All new viral sequences obtained form a monophyletic group within HEV genotype 3. These preliminary results reveal a potential circulation of HEV in the pig population. The high proportion of contamination in the pork liver samples highlights a major risk associated with their consumption.

Seafood products are the main dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, due to the widespread use of processed fish products, the presence of these n-3 PUFAs may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, with a focus on n-3 polyunsaturated fatty acids (n-3 PUFAs), in different processed fish and shellfish food of EU and non-EU origin purchased in supermarkets and ethnic food shops in Messina (Italy), using gas chromatography with flame-ionization detector (GC-FID). From the fatty acid profile, the atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.31-9.84 (TI) and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids had the following ranges: 13.55-50.48%, 18.91-65.58%, 13.84-52.73%, respectively. All samples showed a good presence of PUFAs and, in particular, eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the main n-3 polyunsaturated fatty acids (n-3 PUFA).

To remain relevant in the green transition, companies are beginning to voluntarily account for the exchange of emissions in their supply chain transactions and using the resulting greenhouse gas inventories for climate resilient decision support. Market advantages of sustainability and transparency see a shift from internal decision support tools to external communication tools which potentially expose companies to the risk of uncovering greenwashing if claims are not supported by transparent data, sound modelling, and a climate just emissions inventory, which considers external impacts connected to the production system. The different methods and standards in place for such greenhouse gas inventories, despite all referring to the ISO life cycle analysis standards and guidelines, present mixed signals and leave room for different interpretations, that may ultimately lead to cascading greenwashing, misleading results, and false successes. The new GHG Protocol Land Sector and Removals Guidance draft addresses this in part. With the GHG Protocol moving into revision periods, we identify gaps that present barriers to companies, or allow for interpretations that goes against the intentions of reporting GHG emissions related to an activity or organisation. The literature agrees that not rectifying these subtle-ties present counterproductive decision support for the green transition’s overall goal: to reduce global emissions.

Accumulating literature demonstrates that omega-3 polyunsaturated fatty acid (N3PUFA) can be incorporated into the phospholipid bilayer of cell membrane in the human body to positively affect the cardiovascular system, including improving epithelial function, decreasing coagulopathy, and attenuating uncontrolled inflammatory responses and oxidative stress. Moreover, it has been proven that the N3PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of some potent endogenous bioactive lipid mediators that mediate some favorable effects attributed to their parent substances. A linear dose-response relationship between increased EPA and DHA intake and reduced thrombotic outcomes have been reported. The excellent safety profile of dietary N3PUFA makes them a prospective adjuvant treatment for people exposed to a higher risk of cardiovascular problems associated with COVID-19. This review presented the potential mechanisms that might contribute to the beneficial effect of N3PUFA and the optimal form and dose applied.

The main purpose of this article is to consider the smoothness control of a weak solution after some moment if there is known solution regularity until this moment. The necessary tools can be varied. It is possible to control kinetic energy dissipation to fix moment or changing of velocity square or summability of acceleration square to fix at point time.

Cancer is a complex disease, considered a major public health problem worldwide. Among the types of cancer, melanoma, and leukemias present high mortality rates in Brazil and worldwide. Currently, conventional cytotoxic treatments cause severe side effects by the non-selectivity between normal cells and cancer cells. Therefore, molecules of natural origin with more efficient anticancer properties and that present fewer adverse effects are of extreme importance for cancer therapy and improvement in patients’ quality of life. This study isolated, identified, and characterized the chemical structure of a new anthraquinone present in the extract of the roots of Senna velutina. In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina, analyzed by HPLC-DAD, and its molecular structure was determined by NMR. Subsequently, their cytotoxic activity was evaluated by the MTT method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. By flow cytometry technique, the apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2'-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2'-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and CA+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed-cell death pathways induced by 2'-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2'-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.

We analyzed mineralogical characteristics, and major as well as rare earth element concentrations from a cryptotephra layer in sediments of the infilled maar of Auel (Eifel, Germany). The results of detailed geochemical analyses of clinopyroxenes and their glassy rim of the specific layer are most similar to those from the Campanian Ignimbrite (CI) Tephra occurrence in a loess section at Urluia (Romania). Both records show idiomorphic green clinopyroxenes and formation of twisted minerals up to millimeter scale. The cryptotephra in the Auel core has an age of around 39,940 yr b2k in the ELSA-20 chronology, almost identical to the latest Ar/Ar dates for the Campanian Ignimbrite/Y5 eruption. These observations suggest that parts of the CI ash cloud were transported also northwestward into Central Europe, whereas the main branch of the CI ash plume was transported from southern Italy towards the NE, E and SE.

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells. We measured Nlgn3 mRNA neuronal and glial expression via quantitative 3-dimensional image analysis. To validate dual RNAScope/immunofluorescence data, we interrogated available single cell RNA sequencing (scRNASeq) data to assess for Nlgn3, Nlgn1, Nlgn2 and their binding partners, Nrxn1-3, MGDA1 and MGDA2, in enteric neural subsets. Most submucosal and myenteric neurons expressed Nlgn3 mRNA. In contrast to other Nlgns and binding partners, Nlgn3 was strongly expressed in enteric glia, suggesting a role for Neuroligin-3 in mediating enteric neuron-glia interactions. The autism-associated R451C mutation reduces Nlgn3 mRNA expression in cholinergic but not VIPergic submucosal neurons. In the myenteric plexus, Nlgn3 mRNA levels are reduced in calretinin and NOS labelled neurons and S100ß labelled glia. We provide a comprehensive cellular profile for neuroligin-3 expression in ileal neuronal subpopulations of mice expressing the R451C autism-associated mutation in Nlgn3, which may contribute to the understanding of the pathophysiology of GI dysfunction in ASD.

The elderly present age-related morphological and histological changes of the oral cavity; Literature displays many studies regarding the specific pathologies of the oral cavity in elderly patients, but no etiologically based classification is available. The aim of this study was to analyze the series of patients over 65 who were treated by our Unit of Pathology between 2020 and 2022 for a suspicion of oral lesion or for preventive dental evaluation (in anticipation of cardiac surgery, anti-resorptive drugs intake, chemotherapy, radiotherapy of the head-neck district or transplantation). The analysis was conducted by dividing oral lesions into 5 groups depending on the etiology: reactive, immunological, traumatic, benign and malignant degenerative. The sixth group consisted of patients undergoing preventive dental evaluation. The study included 435 patients; 91 of them were diagnosed with a reactive origin pathology, 174 with immunological origin pathology, 48 with traumatic pathology and 86 with degenerative pathology (42 benign and 44 malignant). 36 patients went to our Unit for preventive specialist evaluation. Oral health has a major impact on the daily life of the elderly; The examination of oral mucosa in geriatric patients is a fundamental diagnostic moment to report lesions early, thus allowing easier prevention and treatment.

Enterococcus faecalis is a bacterium that can develop a multidrug resistance profile associated with the community as well as nosocomial-acquired infections. Among the treatment options for these infections are aminoglycosides combined with bacterial cell wall inhibitors such as beta-lactams, since E. faecalis is intrinsically resistant to aminoglycosides. One of its most representative resistance mechanisms is the expression of aminoglycoside-modifying enzymes, such as the aminoglycoside phosphotransferase type IIIa of E. faecalis (EfAPH(3')-IIIa). This enzyme acts by phosphorylating aminoglycosides in an ATP-dependent reaction, modifying the 3' position of hydroxyl groups of these antibiotics. Considering this scenario, 3,092 natural products obtained from the ZINC22 database were analyzed to select molecules with the highest affinity for the nucleotide-binding pocket of EfAPH(3')-IIIa, which could be potential aminoglycoside adjuvants. The molecules that showed the best-score results obtained from ensemble docking-based virtual screening were ZINC000000952700 (BS-1), ZINC000014793040 (BS-2) and ZINC000015498603 (BS-3). The most promising results were for BS-2, a flavone derivative, due to its improved stability profile in molecular dynamics simulation (average values of RMSD of 0.23 nm, and Rg of 1.94 nm), binding free energy calculations (average ΔG total of -35.3 nm), as well as better toxicological profile (lower probability of hepatotoxicity, carcinogenic, immunotoxicity, mutagenicity, and cytotoxicity effects), compared to BS-1 and BS-3. These results allow us to propose that a flavone derivative may act as an adjuvant to aminoglycosides in the treatment of E. faecalis infections, acting as an inhibitor in the nucleotide-binding pocket of EfAPH(3')-IIIa.

Inflammation mediators enhance the activity of connexin (Cx) hemichannels especially in the epithelial and endothelial tissues. As potential release route for injury signals like (oligo)nucleotides, Cx hemichannels may contribute to long lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells using the dye uptake as functional assay. Moreover, possible impact of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (> 5 µM) and Cx46 (> 20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversible inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to stimulation of adenosine signaling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversible block Cx hemichannels. Deciphering the interaction mechanisms with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for a better and safer use in treatment of pathologies that involve Cx hemichannels.

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

Recombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in RGD (arginine-glycine-aspartic acid) sequences, with good processability that is being investigated for regenerative medicine applications. Recently, the biocompatibility and osteogenic ability of β-TCP/RCP (RCP granules combined with β-tricalcium phosphate (TCP) submicron particles) were demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects (three-walled bone defect) created in beagle dogs to investigate tissue responses and subsequent regenerative effects. Micro computed tomography image analysis at 8 weeks postoperatively showed that the amount of new bone after β-TCP/RCP graft was significantly greater (2.2 fold, P&lt;0.05) than that of the control (no graft) group. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including TRAP-positive and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control, and significantly suppressed gingival recession and epithelial downgrowth (P&lt;0.05). These results suggest that β-TCP/RCP is effective as a periodontal tissue regenerative material.

In this paper, we present the interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles and cytisine and salsoline alkaloids. It has been shown that the reaction results in the one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction is affected by the presence of a base and the order in which the reagents are added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity has been carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking shows that the compounds have insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increases the affinity of these substrates for target proteins selected.

Autism Spectrum Disorder (ASD) is characterized by varying degrees of difficulty in social interaction and communication. These deficits are often associated with gastrointestinal symptoms, indicating alterations in both intestinal microbiota composition and metabolic activities. The intestinal microbiota influences the function and development of the nervous system. In individuals with ASD, there is an increase in bacterial genera such as Clostridium, as well as species involved in the synthesis of branched-chain amino acids (BCAA) like Prevotella copri. Conversely, decreased amounts of Akkermansia muciniphila, and Bifidobacterium spp. are observed. Epigallocatechin gallate (EGCG) is one of the polyphenols with the greatest beneficial activity on microbial growth and its consumption is associated with reduced psychological distress. Therefore, the objective of this review is to analyze how EGCG and its metabolites can improve the microbial dysbiosis present in ASD and its impact on the pathology. The analysis reveals that EGCG inhibits the growth of pathogenic bacteria like Clostridium perfringens and Clostridium difficile. Moreover, it increases the abundance of Bifidobacterium spp. and Akkermansia spp. As a result, EGCG demonstrates efficacy in increasing the production of metabolites involved in maintaining epithelial integrity and improving brain function. This identifies EGCG as highly promising for complementary treatment in ASD.

Indole-3-acetic acid (IAA) is a key vegetative hormone that plays crucial roles in plant growth and development. In this study, the effect of the exogenous application of IAA as a biostimulant in the cultivation of onions (Allium cepa) was investigated. Different IAA concentrations were evaluated to determine their effects on onion growth and chemical parameters. Various physical and chemical parameters such as total fresh weight, plant height, chlorophyll content, nitrates, total phenols, and antioxidant capacity (DPPH) were analyzed. The results revealed that exogenous application of IAA had a significant impact on onion growth and quality. Specifically, it was found that certain concentrations of IAA fostered a greater fresh weight of the bulb, an increase in the levels of phenolic compounds and a greater DPPH. However, the onion response to IAA was dependent on the concentration. In conclusion, the present study provides evidence that the exogenous application of IAA as a biostimulant can improve onion growth and quality. These results are relevant for the development of sustainable agricultural practices and could be oriented towards crop improvement.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

Aim: Evaluation of role of supplementation of omega-3 polyunsaturated fatty acids on endothelial function in patients with metabolic syndrome. Methods: Total of 80 patients with metabolic syndrome were enrolled to two groups. We evaluated endothelial function in subjects before and after three-month treatment with omega-3 polyunsaturated fatty acids in dose 2.4g daily (800mg 3 times a day) vs placebo. Using the Endo-PAT2000 device (Itamar Medical Ltd. Caesarea, Israel), reactive hyperemia index – a parameter of endothelial function and augmentation index– a parameter of arterial stiffness were measured. Plasmatic level of glutation peroxidase, homocysteine, apolipoprotein B and lipoprotein (a) were also evaluated. Results: The average values of reactive hyperemia index before the treatment with n-3PUFA was 1.62 ± 0.42 , whereas 1.96 ± 0.62 at the end of the study (p<0.005). Augmentation index changed from 14.66 ± 19.55 to 9.21 ± 15.64 after the treatment (p=0.003). We also observed statistically significant decrease of apolipopotein B (0.94 ± 0.36 vs 1.13 ± 0.35, p = 0.001) and homocysteine (19.31 ± 5.29 vs. 13.78 ± 3.05, p = 0.001) and increase of the glutathion perxidase plasma levels (41.65 ± 8.90 vs. 45.20 ± 8.01), p=0.001. Conclusion: We have observed significant improvement of the endothelial function in subjects with metabolic syndrome treated with omega-3 polyunsaturated fatty acids in dose 2.4g daily.

The fast-paced evolution of artificial intelligence (AI), machine learning (ML), natural language processing (NLP), large language model (LLM) applications, and generative pre-trained transformer (GPT) have set the stage for improved and autonomous project scheduling models. This study demonstrates how project scheduling can be enhanced by employing building information modeling (BIM) to predict reliable schedules for each project element. The research is based on design science research (DSR) methodology and focus group discussion. The proposed system consists of six components: project analyzer, data warehouse, activity identifier and sequencing, activity magnitude and direct cost calculator, activity duration calculator, and schedule analyzer. Unlike other solutions, the proposed solution sequences activities based on an ML model rather than constraint matrices. The proposed solution thus enhances project performance through proactive planning and risk management. Integrating the autonomous project scheduling solution with the other components of an autonomous project management system would surmount schedule challenges and would result in greater cost efficiency and fewer delays.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

Hypercholesterolemia is a major risk for the development of cardiovascular diseases (CVDs), the main cause of mortality worldwide, and it is characterized by high levels of circulating cholesterol. The drugs currently available for hypercholesterolemia control have several side effects, so it is necessary to develop new effective and safer therapies. Seaweeds serve as sources of several bio-active compounds with claimed beneficial effects. Eisenia bicyclis (Aramé) and Porphyra tenera (Nori) are edible seaweeds which were previously recognized as rich in bioactive compounds. In the present study, we aim to evaluate the anti-hypercholesterolemia effect of these two seaweeds ex-tracts and their health potential. Both extracts, but more efficiently Aramé extract demonstrated to have liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitory activity and to reduce approximately 30 % cholesterol permeation through human Caco-2 cells simulating the intestinal lining, targets for hypercholesterolemia treatments. An untargeted metabolomic assay on human intestinal Caco-2 and liver Hep-G2 cells lines exposed to Aramé and Nori extracts revealed changes in the cell’s metabolism as indicators of the extract’s health beneficial effects. The metabolic pathways affected by exposure to both extracts were associated to lipid metabolism, such as phospholipids, and fatty acid metabolism, pathways of amino acid, cofactors and vitamins and cellular respiration metabolism. More profound for Aramé treated cells, but also seen for Nori ex-posed cells, the metabolites modifications were associated with the protection against CVDs and other diseases and, to the improvement of cells oxidative stress tolerance. The results obtained for the anti-hypercholesterolemia properties, in addition to the revelation of the positive impact on cells metabolism, are an important contribution for further evaluation of these seaweeds extracts as functional foods or for CVDs prevention.

Hip joint surgeries, including total hip replacement or resurfacing, have increased tremendously in the last decades. Number of patients of all ages, replace their hip, due to severe injuries or trauma problems, so as to have a better life. According to these factors, new material and processes in implants manufacturing are imported to medicine, through research programs, every year. In the scope of one of these programs, that has to do with ceramic coatings on metallic resurfacing implants, a new 3axis Hip simulator was designed and manufactured in the Laboratory of Manufacturing Technology of the National Technical University of Athens. The scope of this paper is to present the main parts, materials and process used to manufacture the simulator as well as the way the simulator is working and how its movement in 3axis is accomplished. Furthermore, the evaluation of the machine and its use to examine resurfacing implants is presented.

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) with proven health effects, whom bioavailability improvement is becoming a public health issue. Unlike fish oils, the bioavailability of DHA from microalgal (A) has not been fully assessed, particularly with regard to the molecular structuring capabilities offered by A-oil. We explored the impact of 5 formulas rich in DHA, different by i) the molecular structure: ethyl ester (EE) or monoglyceride (MG) or Triglyceride (TG) and ii) the supramolecular form: emulsified TG or TG+phospholipids (blend PL), on the lymphatic kinetics of DHA absorption and the lipid characteristics of resulting lipoproteins. We demonstrated that in rat, the DHA absorption of the conventional A-DHA TG structure was more effective than the EE structure (+ 23%). More, the A-DHA MG and A-DHA Emulsion were the most favourable DHA-vectors (AUC: 89% and +42%, respectively), thanks to an improved lipolysis. The A-DHA MG and -Emulsion presented the richest DHA content in TG (+40%) and PL (+50%) of lymphatic chylomicrons, which could impact the metabolic fate of DHA. We concluded that structuring A-DHA in TG or EE would be more prone for tissue and hepatic metabolism whereas in A-DHA MG and A-DHA Emulsion could target nerve tissues.

Ovarian cysts are linked to hormone imbalances and altered gene expressions, but the connection between cysts and ion channel expression is understudied. This study explored the role of TWIK-related acid-sensitive K+ (TASK) channels in bovine ovarian cyst formation. The ovarian follicles were split into small (5 to 10 mm in diameter) and large (> 25 mm in diameter) groups. Among the measured K+, Na+, and Cl- concentrations in follicular fluid (FF) obtained from small-sized follicles (SF) and large-sized follicles (LF), the K+ concentration was significantly lower in LFFF. Quantitative PCR, western blot, and immunocytochemistry data revealed that TASK-3 expression levels significantly decreased by approximately 50% in both LF and granulosa cells obtained from LF (LFGCs) compared to the corresponding controls. The TASK-3 protein was localized to the plasma membrane of GCs. The diameter of LFGCs was larger than that of SFGC. The cell swelling response to exposure to a hypotonic solution (200 mOsm/L) was highly reduced in TASK-3-overexpressing cells compared to vector-transfected cells. TASK-3-knockdown cells showed arrested growth. Senescence markers were detected in LFGCs and TASK-3-knockdown cells. These findings suggest that reduced TASK-3 expression in LF is associated with the inhibition of GC growth, leading to senescence and cyst formation.

Rice bran arabinoxylan compound (RBAC) is derived from rice bran enzymatically treated with Lentinus Edodes mycelium. This review explores biologically active compounds and mechanisms of action that support RBAC as an immunomodulating nutraceutical in generally healthy and/or aging individuals. Thirty-seven (n=37) primary research articles fulfiled the selection criteria for review. Most research is based on Biobran MGN-3, which consists of complex heteropolysaccharides with arabinoxylan as its primary structure while also containing galactan and glucan. RBAC was found to invoke immunological activities through direct absorption via the digestive tract and interaction with immune cells at the Peyer’s patches. RBAC was shown to promote the innate defence by upregulating the macrophage phagocytosis and enhancing natural killer cell activity while lowering oxidative stress. Through induction of dendritic cell maturation, RBAC also augments adaptive immunity by promoting T and B lymphocyte proliferation. RBAC acts as an immunomodulator by inhibiting mast cell degranulation during allergic reactions, attenuating inflammation, and downregulating angiogenesis by modulating cytokines and growth factors. RBAC is shown to be a safe and effective neutraceutical for improving immune health, notably in aging individuals with reduced immune function. Human clinical trials with geriatric participants have demonstrated RBAC to have prophylactic benefits against viral infection and may improve their quality of life. Further research should explore RBAC’s bioavailability, pharmacodynamics, and pharmacokinetics of the complex heteropolysaccharides within. Translational research to assess RBAC as an nuetraceutical for the aging population is still required, particularly in human studies with larger sample sizes and cohort studies with long follow-up periods.

Background: Prostate cancer remains a significant global health concern, and understanding the molecular drivers of this disease is crucial for developing effective diagnostic and therapeutic strategies. Steroid Receptor Coactivator-3 (SRC-3), a member of the SRC family, has emerged as a key player in prostate cancer pathogenesis. This review comprehensively examine the role of SRC-3 in prostate cancer, encompassing molecular mechanisms, clinical implications, and therapeutic opportunities. Methods: A systematic literature search following PRISMA guidelines was conducted in PubMed, PMC, and other relevant databases to identify studies that investigate SRC-3 in prostate cancer. A total of 67 articles were selected based on predetermined inclusion criteria. Results: 785 articles were retrieved from databases using specific keywords and MeSH terms related to SRC-3 and Prostate Cancer. After removing 461 duplicates, 260 articles were excluded based on title and abstract review. Subsequently, a comprehensive screening by three researchers resulted in 47 relevant articles for this systematic review. We summarize its contributions to AR-mediated transcriptional regulation, tumor growth, and metastasis. Evidence suggests that SRC-3 expression correlates with prostate cancer aggressiveness, disease recurrence, and poor patient outcomes. Its potential as a diagnostic biomarker and therapeutic target is explored, offering insights into personalized medicine approaches. Conclusions: SRC-3 plays a pivotal role in prostate cancer, influencing disease progression and clinical outcomes. Understanding the molecular intricacies of SRC-3 in prostate cancer offers new opportunities for precision medicine and innovative therapeutic approaches. This review provides a comprehensive overview of SRC-3's involvement in prostate cancer, emphasizing its clinical relevance and potential as a therapeutic target, ultimately contributing to improved patient care in the era of personalized oncology.

Allergies are a common and increasing health problem affecting millions of people worldwide. In addition to genetic predisposition, this increase in allergic cases is attributed to air pollution, climate change, more time spent indoors, lack of physical activity, and alterations in eating habits. The Mediterranean diet (MD), which includes a lot of fruits and vegetables, whole grains, legumes, nuts, olive oil and fish has been linked to a variety of health benefits, including a lower risk of chronic and allergic diseases. The purpose of this paper is to explore the effects of the dietary components of the MD on food allergies. Electronic databases PubMed, Scopus, Science Direct, and EBSCO were used to conduct this systematic review up to March 2023. 696 studies were initially identified and nine were included (five human and four animal studies). The findings of this review showed an overall beneficial effect between the food components of the MD and food allergies. Although the results are promising, the limited number of studies highlights the need for more research.

Animal-assisted pedagogy (AAP) is well known in classroom practice, but scientific evidence is still lacking. At the same time, the biggest challenge in education systems worldwide is the social in-tegration of students. In a pre-post design, 30 heterogeneous students (16f/14m) from four different school classes (grades 5-7) were interviewed (problem-centred interview) about their social inclu-sion and their social climate in class before and after being taught selected subjects with a school dog (of different breeds) for one school term. At the second measurement point, they were also asked about their perception of AAP. The data was analysed both qualitatively (Kuckartz) and in terms of the number of quotes on the main topics using MAXQDA analysis software. The presence of a dog in the classroom leads to an improved social climate and more social integration. In ad-dition, the perception of the other students and the teacher changes to a more positive and friendly image. Through AAP, a new social role is added to the classroom, where caring and bonding are prioritised. Social interaction and norms are influenced and sterotypical and individual roles can be changed. Therefore, AAP can be a key to promoting social inclusion in the school environment.

Covariant integral quantization with rotational symmetry SO(3) is established for the quantum motion on this group manifold, or, alternatively, for Gabor signal analysis on this group. We revisit the action of the related (non-unitary) Weyl-Gabor operator on the Hilbert space of square integrable functions on SO(3) and disclose a set of various properties. By selecting weight functions on the corresponding discrete-continuous phase space, one derives related coherent states and Wigner transform.

Fluorinated compounds and co-enzymes are being widely researched and employed throughout research community because of their versatile physical, chemical and biological properties. In this work, we synthesized NiS-NiO/S-g-C3N4, a highly effective photocatalyst for C(sp3)-F bond activation and the regeneration of coenzyme (1,4-NADH) employing a new and ecologically acceptable route. The obtained photocatalyst exhibited important photocatalytic properties, such as good solar light harvesting ability, suitability of the optical band-gap, and facilitating efficient charge migrations. As a result, the newly designed NiS-NiO/S-g-C3N4 photocatalyst shows the excellent yield for regenerations of 1,4-NADH (51%). Further, a method of combining C(sp3)-F bond activation with photocatalysis has been demonstrated that represents a very powerful and sustainable approach, that can be a major breakthrough for the field of pharmaceutical.

Rice bran arabinoxylan compound (RBAC) is a polysaccharide modified by Lentinus edodes mycelial enzyme widely used as a nutraceutical. To explore translational research on RBAC, a scoping review was conducted to synthesise research evidence from English, Japanese, Korean, and Chinese sources while combining bibliometrics and network analyses for data visualisation. Ninety-eight articles on RBAC and the biological activities related to human health or disease were included. Research progressed with linear growth (median=3/year) from 1998 to 2022, predominantly on Biobran MGN-3 (86.73%) and contributed by 289 authors from 100 institutions across 18 countries. Clinical studies constitute 61.1% of recent articles (2018 to 2022). A shifting focus from immuno-cellular activities to human translations over the years was shown via keyword visualisation. Beneficial effects of RBAC include immunomodulation, synergistic anticancer properties, hepatoprotection, antiinflammation, and antioxidation. Cancer patients reported reduced side effects from chemoradiotherapy and improved quality of life in human studies, indicating RBAC’s impact on the psycho-neuro-immune axis. RBAC has been studied in 17 conditions, including cancer, liver diseases, HIV, allergy, chronic fatigue, gastroenteritis, cold/flu, diabetes, and in healthy participants. Further translational research on the impact on patient and community health is required for the evidence-informed use of RBAC in health and disease.

This report provides a comprehensive overview of occupational asthma and respiratory hypersensitivity, focusing on some chemicals used in the workplace Includes numerous case studies and research papers related to occupational exposure methacrylates, such as HEMA-HPMA, and respiratory hypersensitivity are discussed And the relationship is explored The book also examines asthma pathophysiology, emerging drug delivery systems used to treat asthma, and the potential of nanoparticles , dendrimers and micellar systems have to improve pulmonary drug delivery in detail The worldwide prevalence of asthma is highlighted, with higher rates in high-GDP countries. The book highlights the need to improve asthma diagnosis, treatment and biomarkers, particularly in rural and low-income countries where the disease is often underdiagnosed and inadequately treated, and discusses the role of inflammation in asthma, in particular secondary inflammation characterized by specific cytokines and inflammation cells In addition, the paper explores various drug delivery methods, such as parenteral and parenteral drugs, pressurized inhalers (pMDIs), dry powder inhalers ( DPIs), nebulizers, nanoparticles, liposomes, micellar systems, microparticles , dendrimers, and gene therapy . These systems aim to increase pulmonary delivery of drugs and improve clinical outcomes. The potential of dendrimer bilirubin-based nanoparticles and micellar systems in the treatment of asthma and lung inflammatory diseases, including asthma, has been discussed in summary, this paper provides an overview of occupational asthma and respiratory hypersensitivity, and this discussion highlights the association between methacrylate exposure and respiratory hypersensitivity.

Introduction: The objective of the study is to assess the failure of therapies with HFNO (High-Flow Nasal Oxygen), CPAP, Bilevel or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: Retrospective and observational study of SARS-CoV-2 positive patients who required non-invasive respiratory support (NIRS), at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11,8%) were included. 95 of them failed this therapy (48,3%). We objectivated that during hospitalization in the ward the combined therapy with HFNO and CPAP had a lower failure rate overall and the highest treatment purely with Bilevel (p = 0,005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP and combined therapy of HFNO with CPAP, (35,6% of patients) presented a 24,2% failure compared to those who did have two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64,4% of patients) with 75,8% associated failure (OR: 0, 374; CI 95%: 0,203-0,688. p=0,001).Conclusions: The use of NIRS in conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy with Bilevel increases the probability of failure, with the combined therapy strategy with CPAP and HFNO being the most promising option.

Galectins are β-galactosyl-binding proteins that fulfill essential physiological functions. Recently, we introduced galectin-1 (Gal-1) and galectin-3 (Gal-3) as fusion proteins of a His6-tag, a SNAP-tag, and a fluorescent protein. We characterized their binding in ELISA-type assays and their application in cell-surface binding. In the present study, we have constructed further fusion proteins of galectins with fluorescent protein color code. The fusion proteins of Gal-1, Gal-3, and Gal-8 were purified by affinity chromatography. For this, we have prepared glycoprotein affinity resins based on asialofetuin (ASF) and fetuin and combined this in a two-step purification with Immobilized Metal Affinity chromatography (IMAC) to get pure and active galectins. Purified galectin fractions were analyzed by size-exclusion chromatography. The binding characteristics to ASF of solely His6-tagged galectins and galectin fusion proteins were compared. As an example, we demonstrate a 1.6-3-fold increase in binding efficiency for HSYGal-3 (His6-SNAP-yellow fluorescent protein-Gal-3) compared to the HGal-3 (His6-Gal-3). Our results reveal an apparent higher binding efficiency for galectin SNAP-tag fusion proteins compared to His6-tagged galectins which are independent of the purification mode. This is also demonstrated by the binding of galectin fusion proteins to extracellular glycoconjugates laminin, fibronectin, and collagen IV. Our results indicate the probable involvement of the SNAP-tag in apparently higher binding signals, which we discuss in this study.