We have studied the very large amount of literary works written by the Italian mystic Maria Valtorta to assess similarities and differences in her writings because she claims that most of them are due to mystical visions. We have used mathematical and statistical tools developed for specifically studying deep linguistic aspects of texts. The general trend indicates that the literary works explicitly attributable to Maria Valtorta differ significantly from her other literary works, that she claims are attributable to the alleged characters Jesus and Mary. Mathematically, they seem to have been written by different authors. The comparison with the Italian literature is very striking. A single author, namely Maria Valtorta, seems to be able to write texts so diverse to cover the entire mathematical range (suitable defined) of the Italian literature of seven centuries.

The relationship between epicardial adipose tissue (EAT) and atrial fibrillation (AF) has gained interest in recent years. Previous literature on the topic presents great heterogeneity, focusing especially on computed tomog-raphy imaging. Aim of the present study is to determine whether an increased volume of left atrial (LA) EAT evaluated at routine pre-procedural cardiac magnetic resonance imaging (MRI) relates to AF recurrences after catheter ablation. 50 patients undergoing AF cryoballoon ablation and pre-procedural cardiac MRI allowing quantification of LA EAT were enrolled. In one patient segmentation of LA EAT could not be achieved. After a median follow-up of 16.0 months, AF recurrences occurred in 17 patients (34%). Absolute volume of EAT was not different in patients with and without AF recurrences (10.35 ml vs. 10.29 ml; p-value=0.963), whereas volume of EAT indexed on the LA (EATi) was lower, albeit non statistically significant, in patients free from arrhythmias (12.77% vs. 14.06%; p-value=0.467). Receiver operating characteristic curve testing the ability of EATi to predict AF recurrence after catheter ablation showed sub-optimal performance (AUC: 0.588). The finest identified cut-off of EATi was 10.65%, achieving a sensitivity of 0.5, a specificity of 0.82, a positive predictive value of 0.59 and a negative predictive value of 0.76. Patients with values of EATi lower than 10.65% showed greater survival free from arrhythmias than patients with values above this cut-off (84% vs. 48%; p-value=0.04). In conclusion, indexed LA EAT volume evaluated at cardiac MRI independently relates to arrhythmia recurrence after AF cryoballoon ablation.

Radial nerve palsies present a challenging clinical scenario, often leading to substantial functional impairment. This study focuses on evaluating the outcomes of tendon transfer surgeries in patients with post-traumatic radial nerve injuries. The radial nerve, vital for upper limb movements, faces various etiologies such as trauma, compression, or idiopathy. Patients with radial nerve palsy encounter difficulties in daily activities, emphasizing the need for effective management strategies. The research introduces a novel evaluation protocol, aiming to comprehensively assess tendon transfer outcomes. This protocol incorporates functional movements of wrist and finger joints, encompassing both objective and subjective parameters. The retrospective study includes eleven patients treated between 2010 and 2022, with a minimum follow-up of one year post-surgery. Tendon transfers demonstrated positive results. The evaluation protocol covers a wide range of parameters, including wrist and finger mobility, thumb function, grip strength, and patient satisfaction. The results indicate successful restoration of motor function, with an average grip strength of 70% compared to the healthy arm. The proposed evaluation protocol facilitates standardized and reproducible assessment, minimizing subjective errors in clinical evaluations. Despite the study's limitations, such as a relatively small sample size, the findings underscore the effectiveness of tendon transfers in treating radial nerve palsies. The introduced evaluation scheme provides a comprehensive and reproducible approach to assess outcomes, contributing to the global standardization of tendon transfer assessments in radial nerve injuries.

Menin inhibitors are new and promising agents currently in clinical development that target the HOXA/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemia. The mechanism of action of this new class of agents is based on the disruption of menin-KMT2A complex (constitute of chromatin remodelling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or mutated NPM1. This new class of drugs has been tested alone, or in combination with synergistic drugs, in phase I and II clinical trials (AUGMENT-01 and 02, KOMET-01 and 07, SAVE, COVALENT trial and others), showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this review, we summarise the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data of this emerging and promising class of agents, in particular revumenib and ziftomenib.

The fish fauna of Rio de Janeiro has been extensively studied, resulting in a comprehensive database of species collected over more than three centuries. This study aimed to identify fish species, their locations, and compile scattered information to aid in climate action and freshwater conservation prioritization and an evaluation of the sampling effort to date, as well as to identify patterns of diversity and distribution of freshwater ichthyofauna, delineate biogeographic units, and explore similarity relationships between areas. Analyzing data from nearly 25 ichthyological collections and literature on original species descriptions revealed 346 fish species: 172 freshwaters native, 22 allochthonous, and 152 marine species. The checklist includes updated species names. The sampling effort in Rio de Janeiro is high, especially in coastal lowlands. The findings indicate that inventory work is still needed in certain areas. Five bioregions of freshwater ichthyofauna were identified, along with six major areas of higher species richness. This biogeographic assessment underscores the diverse and distinctive freshwater fish fauna in the basins of Rio de Janeiro, with well-defined biogeographic units.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

In recent years, the widespread introduction of bike-sharing systems in China has had a profound impact on the daily lives of Chinese citizens and the development of the urban transport system. This article attempts to analyse the impact of this phenomenon on sustainability. The gradual improvement of related monitoring measures has facilitated the maturation of the bike-sharing industry from the initial stage of uncontrolled growth to the current stage of standardised management. By tracing the global development of bike-sharing systems with a special focus on China, this study sheds light on the platformisation of bicycles and its multiple impacts on technical, environmental, cultural, economic and social sustainability. Furthermore, the study provides a comprehensive analysis of the transformation of bicycles in China and highlights the diverse impacts of platform-based bike sharing on various facets of Chinese society. The development of different bike-sharing systems in China is a unique and crucial case to interpret the current situation of bike-sharing and imagine future scenarios. In contrast to the prevailing and uniform approach derived from the experiences of Northern European countries, the massive and widespread experimentation with different bike-sharing schemes in China reveals not only potentials and aspects of sustainability, innovation and urban and social regeneration, but also some hidden shadows similar to those in small-scale contexts such as Northern Europe. Furthermore, the study emphasises the crucial role of sustainable development principles in addressing urban challenges specific to China.

Understanding the structure and properties of MgCl2/TiCl4/ID nanoclusters is a key to uncover the origin of Ziegler-Natta catalysis. In this work MgCl2/TiCl4 nanoplatelets derived by machine learning and DFT calculations have been used to model the interaction with ethyl-benzoate EB (as internal donor) with available exposed sites of binary TixCly/MgCl2 systems. The influence of vicinal Ti2Cl8 and coadsorbed TiCl4 on energetic, structural and spectroscopic behaviour of EB has been considered. The adsorption of homogeneous-like TiCl4EB and TiCl4(EB)2 at the various surface sites have been also simulated. Calculations have been carried out by employing B3LYP-D2 and M06 functionals. The adducts have been characterized by computing IR and Raman spectra that have been found to provide specific fingerprints useful to identify surface species; IR spectra have been successfully compared to available experimental data.

“De-[Constructing] Growth” is offered as a deeper and more useful conceptualization that avoids the negative connotations of, and resistance to, “degrowth” by decoupling profit from unsustainable consumption, production, and inequality.

Virgin coconut oil (VCO) is a functional food with important health benefits. Its economic interest encourages fraudsters to deliberately adulterate VCO with cheap and low-quality vegetable oils for financial gain, causing health and safety problems for consumers. In this context, there is an urgent need for rapid, accurate and precise analytical techniques to detect VCO adulteration. In this study, the use of Fourier Transform Infrared (FTIR) spectroscopy combined with Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS) methodology was evaluated to verify purity or adulteration of VCO with reference to several low-cost commercial oils such as sun-flower, maize and peanut oils. Control charts were developed to assess the purity of oil samples using MCR-ALS scores values calculated from a data set of pure and adulterated oils. In addition, quantification models were developed using MCR-ALS with correlation constraint for adulterated coconut oil to assess the blend composition. Different data pre-treatment strategies were tested in order to best extract the information contained in the sample fingerprints, and the calibration models were optimised using a genetic algorithm (GA) to select the most important variables. The models gave satisfactory results in external validation procedure, with absolute errors of less than 4.6 % for samples adulterated with sunflower, maize and peanut oils.

Polyalcohol liquefaction can be done by acid or basic catalysis producing polyols with different properties. This study compared the mechanical properties of foams produced using polyols from liquefied Cytisus scoparius obtained by acid and basic catalysis and using two different foam catalysts. The differences were monitored using FTIR analysis. Acid-catalyzed liquefaction yielded 95.1 %, with the resultant polyol having an OH index of 1081 mg KOH/g while basic catalysis yielded 82.5 %, with a similar OH index of 1070 mg KOH/g. Generally, compressive strength with dibutyltin dilaurate (DBTDL) ranged from 16 - 31 kPa (acid-liquefied polyol) and 12 -21 kPa (base-liquefied polyol), while with stannous octoate (TIN), it ranged from 17 - 42 kPa (acid) and 29 - 68 kPa (base). Increasing water content generally decreased the compressive modulus and strength of foams. Higher water content led to a higher absorption at 1670 cm-1 in the FTIR spectrum due to the formation of urea. Higher isocyanate indices generally improved compressive strength, but high amounts led to unreacted isocyanate that could be seen by a higher absorption at 2265 cm-1 and 3290 cm-1. DBTL was shown to be the best foam catalyst due to higher trimer conversion seen in the spectra by a higher absorption at 1410 cm-1. Acid and base-derived polyols lead to different polyurethane foams with different FTIR spectra, particularly with a higher absorption at 1670 cm-1 for foams from acid-derived liquefaction.

This work deals with the synthesis of bare and curcumin (CUR)-loaded chitosan (CS)-based macroparticles by ionic gelation using sodium hydroxide (NaOH) or sodium tripolyphosphate (TPP) as cross-linking agents. The resulting spherical-shaped macroparticles were studied using various characterization techniques, Scanning Electron Microscopy (SEM), Fourier Transformed Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). The release of CUR from the CS-based particles with respect to time was analyzed, and the encapsulation efficiency and degree of swelling were studied. All formulations showed excellent CUR trapping efficiency, exceeding 90%. In particular, the TPP-crosslinked macrobeads released 34 wt% of the charged CUR within minutes, while the remaining 66 wt% was released slowly due to the biodegradation of CS. The results indicate that the correct choice of gelling agent and its concentration leads to spherical particles capable of encapsulating CUR and releasing it in a wide range of kinetics depending on the specific application.

Summary— Introduction: HIV (human immunodeficiency virus) is a virus that attacks and destroys one type of white blood cell, in particular, the CD4 lymphocytes, which are responsible for the body's immune response. This weakens the immune system to such an extent that it can no longer fight other viruses, bacteria, protozoa, fungi, and tumors. Methods: We investigated the potential biological role of the natural compound Polydatin (or piceid) using SwissDock, a web service to predict the molecular interactions that can occur between a target protein and a small molecule. Discussion: For the first time, we have investigated the role of polydatin against HIV-1 protease and HIV-2 protease through a computational approach by comparing their estimated ΔG values (kcal/mol) and the nature of the interactions between the residues in the catalytic center of the HIV proteases.Conclusion: From these simulations, Polydatin has excellent physical properties and an excellent estimated ΔG value (kcal/mol) of about -9.9 kcal/mol against HIV-2 protease and ΔG value (kcal/mol) of about -9.5 kcal/mol against HIV-1 protease. In addition, Polydatin was able to bind to two key amino acids of the catalytic triad sequence common to asparagine proteases (Asp25 and Gly27)

The mutualistic interactions between the oleaginous yeast Lipomyces starkeyi and the green mi-croalga Chloroidium saccharophilum in mixed cultures were investigated to exploit possible syner-gistic effects. As a matter of facts, microalga could act as an oxygen generator for the yeast, while the yeast could provide carbon dioxide to microalga. A lignocellulosic hydrolysate from steam exploded Arundo donax (Giant reed) was used as low cost feedstock. The overall lipid content and lipid productivity obtained in the mixed culture treating the hydrolysate of Arundo donax were equal to 0.081 glipid.gbiomass-1 and 37.2 mglipid.L-1.d-1, respectively. They represented promising re-sults if compared to the model systems where synthetic media were used. This study provided new input for the integration of Single Cell Oil (SCO) production with agro-industrial feedstock and the fatty acid distribution mainly consisting of stearic (C18:0) and oleic acid (C18:1) allows promising applications in biofuels, cosmetics, food additives and other products of industrial interest.

The applicability of the distance aggregation problem has attracted the interest of many authors. Motivated by this fact, in this paper we face the modular quasi-(pseudo-)metric aggregation problem. We characterize those functions that allow merging a collection of modular quasi-(pseudo-)metrics into a single one. Specifically, a description of such functions in terms of triangle triplets is given and, in addition, the relationship between modular quasi-(pseudo-)metric aggregation functions and modular (pseudo-)metric aggregation functions is discussed. Such characterizations are illustrated with appropriate examples. A few methods to construct modular quasi-(pseudo-)metrics are yielded. Several properties of modular quasi-(pseudo-)metric aggregation functions are explored and used to develop quick tests for discarding candidate functions to aggregate modular quasi-(pseudo-)metrics. Moreover, a characterization of those modular quasi-(pseudo-)metric aggregation functions that preserve modular quasi-(pseudo-)metrics is also provided. Furthermore, the relationship between modular quasi-(pseudo-)metric aggregation functions and quasi-(pseudo-)metric aggregation functions is studied in such a way that significative differences are displayed.

This study delves into the therapeutic potential of two natural compounds, Amentoflavone and Bilobetin, by investigating their interactions with the BPIFB4 protein. BPIFB4, a member of the BPI fold-containing superfamily, has been associated with various biological processes, particularly in longevity and cardioprotection( LAV-BPIFB4). Molecular docking analyses revealed promising binding energies for Amentoflavone and Bilobetin with BPIFB4, suggesting favorable interactions.Additionally by pKCSM database are showed the predicted toxicity properties of Amentoflavone and Bilobetin respectively.This research contributes to the growing body of knowledge on natural compounds and their therapeutic implications in the context of vital biological processes. However, these findings underscore the need for further investigations, including in vivo studies and clinical trials, to validate the observed effects and explore the translational potential of Amentoflavone and Bilobetin in promoting cardiovascular health and longevity.

Introduction: VULTO-VAN SILFHOUT-DE VRIES SYNDROME (VSVS;OMIM#615828) is an extremely rare hereditary disease associated with impaired intellectual development and speech, delayed psychomotor development and behavioral anomalies, including autistic behavioral traits and poor eye contact. To date, 27 patients with VSVS have been reported in the world literature. Materials and Methods: We describe a 23y.o. male patient with autism spectrum disorder (ASD) who was admitted to the gastroenterological hospital with signs of pseudomembranous colitis. ASD was first noted in the patient at the age of 2.5y.o. Later he developed epileptic seizers and prominent growth retardation. Prior to the hospitalization he was excluded chromosomal aberrations, Martin-Bell syndrome, aminoacidopathies/aminoacidurias associated with ASD. Whole genome sequencing was prescribed to the patient at 23y.o. Results: The patient appeared to be a heterozygous carrier of “de novo” variant c.662C>T (p.S221L) in ex 4 of the DEAF1 gene. c.662C> T had not been previously described in genomic databases. According to the ACMG criteria this missense variant was considered to be pathogenic. VSVS was diagnosed in the patient. Conclusions: The phenotype of the patient is very similar to the data presented in the world literature. However, growth retardation and cachexia, not previously described in the articles, are of interest.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

Seismic monitoring in areas where induced earthquakes could occur is a challenging topic for seismologists due to generally very low signal to noise ratio. Therefore, the seismological com-munity is devoting several efforts to the development of high-quality networks around the areas where fluid injection and storage and geothermal activities take place, also following the national induced seismicity monitoring guidelines. The use of advanced data-mining strategy, such as template matching filters, auto-similarity search and deep-learning approaches is recently further fostering such a monitoring enhancing the seismic catalogues and lowering the magnitude of completeness of these areas. In this framework, we carried out an experiment where a small-aperture seismic array was installed around the gas reservoir of Collalto, in North Italy. The continuous velocimetric data, acquired for 25 days, were analysed through the application of the optimized auto-similarity search technique FAST. The array was conceived as a cost-effective network, aimed at integrating, right above the gas storage site, the permanent high-resolution Collalto Seismic Network. The analysis allowed to detect micro-events down to magnitude Ml=-0.4 within a distance of ~15km from the array. Our results confirmed that the system based on the array installation and the FAST data-analysis might contribute to lower the magnitude of completeness around the site of about 0.7.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

For the first time, this study identified seven potential ligands with high binding energies through the docking approach against the Crystal Structure of human Melanoma-associated antigen B1 (MAGEB1). The ligands—Imatinib, Bafatinib, Diosmin, Ginkgetin, Bilobetin, Amentoflavone, and Hypericin—showing strong binding energies around -10 kcal/mol, indicate a potentially robust interaction with the target protein. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of these ligands. From these results, the parameters for Diosmin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile, making it a potential candidate for further consideration against Melanoma. Moving forward, it's advisable to conduct further experimental validations, including in vitro and in vivo studies, to confirm the efficacy and safety of Diosmin and other potential ligands. Consideration of pharmacokinetics, metabolism, and specific mechanisms of action will contribute to a comprehensive understanding of these compounds' potential as therapeutic agents.

Therapies targeting amyloid, such as monoclonal antibodies like Lecanemab, Aducanumab, and Donanemab, have garnered FDA approval but remain controversial due to limited clinical benefits and significant side effects against Alzheimer. The present theorical work utilized Virtual Screening and Docking techniques to explore potential small natural molecules' interactions with the KIBRA protein, a promising target for drug development. Kibra protein is considered a biomarker for synaptic dysfunction and cognitive decline. Employing Autodock Vina and Pyrx software, on several natural compounds and found Hypericin to exhibit the lowest binding energy of approximately -9 kcal/mol. Previous studies have highlighted Hypericin's strong affinity for Alzheimer's Disease-associated targets like ABAD and BACE1. These findings suggest Hypericin could be as a potential therapeutic agent for Alzheimer's Disease. Further research is warranted to validate its efficacy and safety for clinical use.

This study investigates the potential antimicrobial utility of the natural substance Amentoflavone against four dangerous bacterial strains—Mycobacterium tuberculosis, Helicobacter pylori, Haemophilus influenzae, and Pseudomonas aeruginosa. Utilizing molecular docking studies, are assessed the binding interactions between Amentoflavone and key protein targets crucial for the viability of these bacteria. The findings suggest promising binding affinities, particularly in the active sites of Aminoglycoside 2'-N-acetyltransferase, Thioredoxin Reductase, N-acetylneuraminate Lyase, and Glucose-1-phosphate Thymidylyltransferase in the respective bacterial strains. While these in silico results provide initial insights, further in vitro and in vivo experiments are essential to validate the biological relevance and efficacy of Amentoflavone as a potential antimicrobial agent against these bacterial pathogens.

The study focused on Molecular Docking simulations using Autodock Vina in conjunction with the Pyrx program to investigate potential drugs and natural compounds against the Bcr-Abl oncoprotein. From initial virtual screening of 200 compounds, 11 potential candidates were selected for further evaluation. Additional investigations included toxicity prediction using the pKCSM server. Among the compounds, Diosmin and Hesperidin showed high maximum tolerated doses in humans and low toxicity. Conversely, only Eltrombopag among the selected drugs exhibited excellent parameters, albeit with a potential risk of liver damage at high dosages. These findings underscore the need for comprehensive evaluation of efficacy and safety in the development of potential treatments targeting the Bcr-Abl oncoprotein.

This study employs molecular docking experiments to investigate the binding interactions of Hypericin with key proteins implicated in Alzheimer's disease (AD). Hypericin demonstrated a significant binding energy of -10.1 kcal/mol with ABAD (3-hydroxyacyl-CoA dehydrogenase type II). The analysis revealed multiple binding interactions, including hydrogen bonds with arginine 6, serine 7, and glutamic acid 140, as well as hydrophobic bonds involving leucine 11, aspartic acid 142, and aspartic acid 86. These findings illuminate the intricate molecular interactions between Hypericin and ABAD, suggesting its potential as a lead compound for further therapeutic development in the context of Alzheimer's disease. Additionally, a parallel docking investigation was conducted for Beta-secretase 1 (BACE1), a protein pivotal in the generation of beta-amyloid peptides—a hallmark of Alzheimer's disease. Inhibiting BACE1 activity is considered a promising therapeutic strategy for AD. Computational analyses suggest that Hypericin may serve as a potential inhibitor of BACE1. Molecular Docking results reveal a robust binding affinity between Hypericin and BACE1, supported by a significant binding energy score of -10.3 kcal/mol. Notably, both ABAD and BACE1 exhibit high binding affinity with Hypericin. This theoretical exploration provides an initial understanding of the intricate molecular pathways involved in Alzheimer's disease and proposes Hypericin as a potential therapeutic compound for mitigating its progression.

Docking results suggest that Amentoflavone has a higher affinity for investigated Serine/threonine-protein kinases, indicating potential interactions that may influence the activities of these kinases. The negative values of the binding energies signify strong and stable interactions, suggesting that Amentoflavone could be a key molecule in modulating the functions of these kinases, which play crucial roles in cellular processes such as cell cycle regulation and apoptosis.

The paper is based on the research project P2Endure funded within the H2020-EE-2016-2017 call. The main aim of the research is to propose innovative solutions for deep renovation that are applicable and replicable for the widest range of building typologies, from public to residential and historic buildings. In this paper, the methodology adopted to perform the energy analyses and to verify the achievement of the expected targets in terms of savings is defined, based on a range of real case studies. The main aim is to promote a guideline for designers showing specific instruments to perform towards the attainment of the 60% threshold of the energy savings giving advice on how to further improve the energy performance of the buildings, basing on the overview of the energy analyses run for similar cases.

The extensive metabolic diversity of microalgae, coupled with their rapid growth rates and cost-effective production, position these organisms as highly promising resources for a wide range of biotechnological applications. These characteristics allow microalgae to address crucial needs in both the agricultural, medical, and industrial sectors. Microalgae are proving to be val-uable in various fields, including the remediation of diverse wastewater types, the production of biofuels and biofertilizers, and the extraction of various products from their biomass. For decades, the microalga Chlamydomonas has been widely used as a fundamental research model organism in various areas such as photosynthesis, respiration, sulfur and phosphorus metabolism, nitrogen metabolism, and flagella synthesis, among others. However, in recent years, the potential of Chlamydomonas as a biotechnological tool for bioremediation, biofertilization, biomass, and bio-products production has been increasingly recognized. Bioremediation of wastewater using Chlamydomonas presents significant potential for sustainable reduction of contaminants and fa-cilitates resource recovery and valorization of microalgal biomass, offering important economic benefits. Chlamydomonas has also established itself as a platform for the production of a wide va-riety of biotechnologically interesting products, such as different types of biofuels, and high-value-added products. The aim of this review is to achieve a comprehensive understanding of the potential of Chlamydomonas in these aspects, and to explore their interrelationship, which would offer significant environmental and biotechnological advantages.

Summary— Introduction: HIV (human immunodeficiency virus) is a virus that attacks and destroys one type of white blood cell in particular, the CD4 lymphocytes, which are responsible for the body's immune response. This weakens the immune system to such an extent that it can no longer fight other viruses, bacteria, protozoa, fungi and tumours. Methods: We investigated the potential biological role of the natural compound Polydatin (or piceid) using SwissDock, a web service to predict the molecular interactions that can occur between a target protein and a small molecule. Discussion: For the first time, we have investigated the role of polydatin against HIV-1 protease and HIV-2 protease through a computational approach by comparing their estimated ΔG values (kcal/mol) and the nature of the interactions between the residues in the catalytic centre of the HIV proteases.Conclusion: From these simulations, Polydatin has excellent physical properties and an excellent estimated ΔG value (kcal/mol) of about -9.9 kcal/mol against HIV-2 protease and ΔG value (kcal/mol) of about -9.5 kcal/mol against HIV-1 protease. In addition, Polydatin was able to bind to two key amino acids of the catalytic triad sequence common to asparagine proteases (Asp25 and Gly27)

This study explores the potential of natural compounds, including Daidzin, Luteolin, and Silibinin, as inhibitors of human monoamine oxidase B (MAO-B) for the treatment of Parkinson's disease. Docking simulations were performed using Autodock Vina with Pyrx program to evaluate the binding affinities of these compounds with MAO-B. Results indicate that Daidzin, Luteolin, and Silibinin exhibit promising binding affinities with MAO-B, with Daidzin demonstrating the highest affinity. Toxicity parameters were further predicted using the PkCSM Server, confirming the low toxicity of these compounds. Overall, the findings suggest that Daidzin, Luteolin, and Silibinin have the potential to be effective and safe treatments for Parkinson's disease through their inhibition of MAO-B. Further experimental validation is warranted to support their therapeutic efficacy in clinical settings.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

To evaluate the nutrient load due to the grazing of laying hens in outdoor runs, soil characteristics were monitored in three Italian organic farms. For each farm, soil samples were taken from three increasing distances from the hen house and two depths and different chemical parameters were evaluated. The comparison among the results from the different distances shows that N-NO3 and Olsen P are the most affected parameters by hen faeces: both present high values with a statistically significant difference in the area close to the poultry house and for the most superficial layer. Even TKN and TOC show significant differences between the concentrations of the first layer (more concentrated) and those of the second layer (less concentrated). In general, the surface soil layer closest to the chicken house is the portion of the outdoor run most affected by chicken droppings and represents the most critical point in terms of potential environmental impact. Therefore, it is necessary to intensify the management of the outdoor run with tools that can facilitate the grazing of animals and with vegetation that can absorb nutrients by limiting leaching and run-off.

Antibiotics have played a crucial role in the reduction of TB incidence globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline of antibiotic development, and different economic and social conditions. In this review, we summarise recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasise that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throught the community.

The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multiresistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.

Hazelnut shells (HS), scientifically known as Corylus avellana L. shells, are a waste produced in companies that process nuts. The main objective of this study was to find an efficient way to maximize the chemical potential of HS by solubilizing the hemicelluloses, which could then be used to recover sugars and at the same time increase the lignin content of this material in order to produce adhesives or high strength foams. In order to optimize the pre-hydrolysis process, two different temperatures (160 and 170 C) and times varying from 15 to 180 min were tested. All the remaining solid materials were then liquefied by polyalcohols with acid catalysis. The chemical composition of hazelnut shells was determined before and after the pre-hydrolysis. All the process was monitored by FTIR-ATR by determining the spectra of solids and liquids after pre-hydrolisis and liquefactions steps. The highest solubilization of hazelnut shells was found for 170 C and 180 min, resulting in a 25.8% solubilization. Chemical analysis after the hydrolysis process showed a gradual increase in the solubilization of hemicelluloses as both the temperature and time of the reactor were increased. Simultaneously, the percentages of α-cellulose and lignin in the material also increased with rises in temperature and duration. FTIR-ATR allowed for the detection of significant spectral changes in the hazelnut shells from their initial state to the solid residue and further into the liquefied phase. This confirmed that pre-hydrolysis was effective in enhancing the chemical composition of the material, making it more suitable for the production of adhesives or polyurethane foams with enhanced mechanical strength.

: This study was aimed at assessing adaptation and bonding of discontinuous (short) glass fiber-reinforced composite to intraradicular dentin EverX Flow (GC Corporation, Tokyo, Japan), when used as intracanal composite filling and anchorage instead of traditional fiber posts. (2) Methods: Seventy intact extracted human teeth were endodontically treated and randomly divided into 6 groups (n=10), depending on the materials used in the post space. In Group 1, a 2-bottle universal adhesive G2 Bond Universal + EverX Flow were tested. In group 2, a single-component universal adhesive G-Premio Bond + EverX Flow were used. In groups 3 and 4 the same materials are tested, but after cleaning of the canal walls with 17% EDTA and final irrigation with 5.25% NaOCl Ultrasound Activated. In the last three Groups (5-7) traditional prefabricated GC Fiber Posts 1.6 mm silanized with G-Multi Primer for 1 minute are cemented with a dual-cured composite resin cement (GradiaCore), after ultrasonic irrigation in the groups 6 and 7. In each group, 1 mm-thick slices from each sample (n=10) were cut for light microscope and SEM inspection for study materials adaption to the dentin and for measuring push-out strength of post / cemement material to the dentin / prefabricated post. These results were statistically analyzed: as the data distribution was not normal, the Kruskal-Wallis Analysis of Variance by Ranks had to be applied. The level of significance was set at p<0.05. Results: Push-out forces varied between 6.66-8.37 MPa. No statistically significant differences were recorded among the groups. Microscopic examination showed that ultrasonic irri-gation increased adaptation of the materials to the dentin surface. There was a trend of higher bond strength among the tested groups when EverX Flow was used. Also, the type of failure was more often cohesive when ultrasonic irrigation and two-step adhesive system were used. Conclusions: Within the limitations of this in vitro study, it may be concluded that when EverX Flow was used for intracanal anchorage in the post-endodontic recon-struction, similar push-out retentive forces and strength to those of traditional fiber posts cemented with particulate filler resin composite cements were achieved. Although further studies are necessary, EverX Flow represents an effective alternative to traditional fiber post adhesion in particular when used in combination with the two-step adhesive system and ultrasonic activation.

Efficient use of agricultural wastes and by-products, basically transforming waste materials into value added products, is considered as pivotal for an effective bioeconomy strategy for the rural development. To this scope, citrus waste management represents a major issue for citrus processors but, at the same time, it embodies a potentially unexploited resource for the rural sustainable development. This study focuses on analyzing the current management of citrus waste in South Italy and identifying the determinants and barriers that may affect an entrepreneur’s choice on the destination of citrus waste. Citrus processors’ preferences about the contract characteristics needed to take part in a co-investment scheme have been investigated. Both analyses are preliminary steps to design an innovative and sustainable citrus by-product supply chain. Results show that the distance between the citrus processors and the citrus by-products plant is one of the main criteria for choosing alternative valorization pathways. Moreover, the required guaranteed capital, the short duration of the contract, and low risk are contract scheme characteristics that improve entrepreneurs’ willingness to co-invest in the development of a citrus waste multifunctional plant.

Recurrent pregnancy loss (RPL) affects around 2 % of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene polymorphisms have been associated with RPL. Some polymorphisms are increased in women of Asian or Caucasian race. In admixed RPL populations, the information on possible genetic links is scarce and contradictory. The study aimed to assess the frequency of two SNP in different enzymes involved in medical conditions observed during pregnancy. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics. It is present in ovaries, and it is hormonally regulated. The endothelial nitric oxide synthase forms nitric oxide from arginine and is involved in vascular tone. Two SNPs, rs1051740 and rs1799983, were assessed. The study included 26 controls and 63 primary RPL patients. Significant differences were observed in the frequencies of both SNP (p<0.05). The frequency of mutated alleles was higher in patients. Double mutated homozygotes were encountered only in RLP patients (p<0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

Verminosis causes great damage to the producer, with reduced milk production and decreased development of young animals. The use of bioproducts are an alternative to control worms. This study evaluated the effects of oral administration of one commercial formulations, based on the fungus Duddingtonia flagrans (Bioverm®) and experimental formulations D. flagrans associated with Pochonia chlamydosporia, on the control of worms in naturally infected cattle on February pasture to October 2021. Eighteen Holstein x Zebu cattle were divided into groups of six animals (group 1 Bioverm®, group 2 Association and control), separated into paddocks naturally infected with helminth larvae (L3). The parasite load was by means of fecal samples and pasture collection to determine L3 infestation. The study demonstrated low recovery of L3 in the pasture due to low rainfall during the experiment. The EPG was lower in groups 1 and 2 compared to the control in April, May and July, while in March the values were lower only in treatment 1 compared to the control. Individual or combined administration of fungal products reduced the presence of eggs and larvae in pastures at certain months of the year, indicating their effectiveness in the strategic control of gastrointestinal parasites in cattle.

Use of porous titanium (Ti) and Ti alloys in orthopedic implants or in light structures requires processing routes that could generate an as-much-as possible control in the pores amount, shape, size and connectivity. In this work, a colloidal approach to the processing of Ti porous structures by the inside foaming of a porogen into a gelled high solid content aqueous suspension of Ti powders, is presented. The prepared slurries contained different amounts of Methyl Cellulose (MC) as gelling agent (8, 10 and 12 g/L) and ammonium bicarbonate (BA) as porogen (15, 20, 25 wt. %). The gel-casted samples were heated at mild temperatures ranging (60, 70 and 80 °C) to promote the gelation and produce, at the same time, the porosity by the thermal decomposition of the ammonium bicarbonate. Different structures are obtained depending on the combination of the study variables

A large body of evidence reports about the positive effects of physical activity in pathophysiological conditions associated with aging. Physical exercise, alone or in combination with other medical therapies, unquestionably causes reduction of symptoms in chronic non-transmissible diseases often leading to significant amelioration or complete healing. The molecular basis of this exciting outcome, however, remain largely obscure. Epigenetics, exploring at the interface between environmental signals and the remodelling of chromatin structure, promises to shed light on this intriguing matter possibly contributing to the identification of novel therapeutic targets. In this review, we shall focalize on the role of sirtuins (Sirts) a class III histone deacetylases (HDACs) which function has been frequently associated, often with a controversial role, to the pathogenesis of aging-associated pathophysiological conditions including cancer, cardiovascular, muscular, neurodegenerative, bones and respiratory diseases. Numerous studies, in fact, demonstrate that Sirt-dependent pathways are activated upon physical and cognitive exercises linking mitochondrial function, DNA structure remodelling and gene expression regulation to designed medical therapies leading to tangible beneficial outcomes. However, in similar conditions, other studies assign to sirtuins a negative pathophysiological role. In spite of this controversial effect, it is doubtless that studying sirtuins in chronic diseases might lead to an unprecedented improvement of life quality in the elderly.

One of the most critical aspects in introral impression is the detection of the finish line, in particular in case of subgingival preparations. The aim of these in vitro study was to evaluate the accuracy among four different IntraOral Scanners (IOSs) in scanning a subgingival vertical margins preparation (VP). A reference maxillary typodont (MT) was fabricated with a VP for full crown on #16 and #21. The MT was scanned with a laboratory scanner (Aadva lab scanner, GC, Tokyo, Japan) to obtain a digital MT (dMT) in .stl format file. A group of 40 digital casts (dIOC) were obtained by scanning the MT 10 times with four different IOSs (Trios 3, 3Shape A/S), ( I700, Medit), (Vivascan, Ivoclar), (Experimental IOS, GC). All the obtained dIOCs were imported into an inspection software program (Geomagic Control X; 3D SYSTEMS) to be superimposed to the dMT, to calculate trueness. Therefore, in order to calculate precision all the scans of the same scanner group were superimposed onto the cast that obtained the best result of trueness. Results were collected as root mean square value (RMS) on #16 and #21 abutment surfaces and on a marginal area positioned 1 mm above and below the gingival margin. A nonparametric analysis Kruskal-Wallis test was performed to compare the RMS values obtained in the different iOS groups for trueness and precision. Statistically significance was set at 0.05. The trueness on #16 abutment, did not statistically differ in between the IOS, while on #21 abutment, Vivascan (56.0 ±12.1) and Experimental IOS, GC (59.2±2.7) performed statistically better than the others. Regarding precision Experimental IOS, GC and Trios 3 were significantly better than I700 and Vivascan both in the #16 (10.7±2,1; 15.8 ± 2,7) and in the #21 area (16.9±13.8 ; 18.0±2.7). At marginal level for both #16 and #21 all the IOS reported reduced accuracy compared to clinical acceptance.

In Mexico viticulture represents the second source of employment in the agricultural area after the fruit and vegetable sector. In developed countries, remote sensing is widely used for vineyard monitoring, however, this tool is barely used in developing countries of Iberoamerica. In this re-search, our overall objective is to characterize two vineyards in the state of Queretaro (Mexico) using Sentinel-2 and meteorological data, specifically spectral and thermal indices. Results showed that spectral indices obtained from Sentinel-2 bands have characterized adequately the phenolog-ical evolution of the different varieties of the vineyards. The Modified Soil-Adjusted Vegetation Index (MSAVI) was adequately used to discriminate the first stages of vineyards, while the Nor-malized Difference Vegetation Index (NDVI) was useful to monitor vineyards during the rest stages of vineyards. Thermal indices have shown that the best grape varieties were those that can adapt to both cooler and warmer temperatures, have a reasonable ripening period, and can produce wines with balanced acidity and flavors. In conclusion, the combination of meteorological (including thermal indices) and remote sensing data (NDVI and MSAVI) provide information for choosing the suitable grape variety for this region.

High-frequency neuroelectric signals like electroencephalography (EEG) or magnetoencephalography (MEG) provide a unique opportunity to infer causal relationships between local activity of brain areas. While causal inference is commonly performed through Classical Granger causality (GC) based on multivariate autoregressive models, this method may encounter important limitations (e.g. data paucity) in the case of high dimensional data from densely connected systems like the brain. Additionally, physiological signals often present long-range dependencies which commonly require high autoregressive model orders / number of parameters. We present a generalization of autoregressive models for GC estimation based on Wiener-Volterra decompositions with Laguerre polynomials as basis functions. In this basis, the introduction of only one additional global parameter allows to capture arbitrary long dependencies without increasing model order, hence retaining model simplicity, linearity and ease of parameters estimation. We validate our method in synthetic data generated from families of complex, densely connected networks and demonstrate superior performance as compared to classical GC. Additionally, we apply our framework to studying the directed human brain connectome through MEG data from 89 subjects drawn from the Human Connectome Project (HCP) database, showing that it is able to reproduce current knowledge as well as to uncover previously unknown directed influences between cortical and limbic brain regions.

Load balancing, energy efficiency and fault tolerance are among the most important data dissemination issues in Wireless Sensor Networks (WSNs). In order to successfully cope with the mentioned issues, two main approaches (namely, Data-centric Storage and Distributed Data Storage) have been proposed in the literature. Both approaches suffer from data loss due to memory and/or energy depletion in the storage nodes. Even though several techniques have been proposed so far to overcome the mentioned problems, the proposed solutions typically focus on one issue at a time. In this paper, we integrate the Data-centric Storage (DCS) features into Distributed Data Storage (DDS) mechanisms and present a novel approach, denoted as Collaborative Memory and Energy Management (CoMEM), to overcome both problems and bring memory and energy efficiency to the data loss mechanism of WSNs. We also propose analytical and simulation frameworks for performance evaluation. Our results show that the proposed method outperforms existing approaches in various WSN scenarios.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

Here, using the theory of electrical-quantum modelling of the neutron and proton as a three-phase alternating current electrical generator, we will analyse the proton decay and the inverse neutron decay and determine the following subatomic particles, Dproton, Protoniu, Dneutron and Neutroniumd.

This study employs molecular docking simulations using Autodock Vina with the Pyrx program to investigate the binding interactions between Human prostate-specific antigen (PSA) and natural compounds, namely Amentoflavone, Ginketin, Rutin, and Hypericin. The evaluation reveals excellent binding energy values, averaging around -10 kcal/mol, suggesting robust and favorable interactions between the selected compounds and PSA. The results provide valuable insights into the potential therapeutic applications of these natural compounds in the context of prostate cancer treatment or management. Further experimental validation is warranted to confirm these findings and explore the viability of these compounds as promising candidates for innovative therapeutic strategies. This research contributes to the growing body of knowledge in the field of molecular docking and its applications in drug discovery and bioinformatics.

Parkinson's disease is a neurodegenerative disorder resulting from progressive damage to specific brain regions. Key symptoms encompass involuntary movements (tremor), slowness of movements (bradykinesia), and muscle rigidity. Although the precise cause remains uncertain, a combination of genetic and environmental factors is believed to contribute to its development. This study focuses on the interaction of the E3 ubiquitin-protein ligase parkin with natural compounds. Docking investigations revealed that Amentoflavone exhibited an excellent binding energy score of approximately -10 kcal/mol. The E3 ubiquitin-protein ligase parkin displayed a robust binding affinity with docked amentoflavone, evident from a high binding energy of -10 kcal/mol. Nonetheless, additional biological studies are crucial not only to validate its potential efficacy against Parkinson's and assess safety in terms of toxicity but also to perform further computational analyses confirming these preliminary assessments.

This study employs molecular docking techniques to investigate a spectrum of targets within Escherichia coli (E. coli), with a specific focus on four key proteins: Beta-lactamase, MccE protein, Penicillin G acylase, and DNA polymerase II. The research explores the binding interactions of various natural compounds, emphasizing Hypericin. Through computational analyses, the study aims to unveil the potential interactions between these compounds and essential proteins in E. coli. Notably, Hypericin demonstrates remarkable binding energy scores of approximately -10.5 kcal/mol within the Ligand Binding Site of the specified proteins. This observation suggests Hypericin's potential as a potent modulator of E. coli targets, prompting further investigation into its antimicrobial properties and therapeutic applications.

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation explores the binding capabilities of Bromelain to Apoptosis-associated speck-like containing CARD (ASC), a crucial adapter molecule known for its involvement in inflammatory processes and inflammasome formation. For the first time, these findings suggest that Bromelain exhibits a notable affinity for ASC, indicating its promising role as a natural anti-inflammatory agent. This study sheds light on the molecular interactions that may contribute to Bromelain's therapeutic potential in modulating inflammatory responses.

This study centered on examining 60 different antibiotics by assessing their primary toxicity parameters through the pkCSM database. The parameters included Max. Tolerated Dose (Human) (log mg/kg/day), Oral Rat Acute Toxicity (LD50) (mol/kg), Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day), and Minnow Toxicity (LC50) (log mM). The results highlight four potential antibiotics—cefotaxime, ceftriaxone, imipenem, and meropenem—that exhibited lower toxicity effects compared to other compounds. These findings imply a relatively favorable safety profile for these antibiotics concerning the specified toxicity parameters. However, it is crucial to interpret these outcomes within the context of the specific clinical application and to consider additional factors for a comprehensive safety assessment. It's essential to acknowledge that evaluating toxicity is intricate, and the determination of what is considered "less toxic" can rely on specific criteria and the context of use. Furthermore, individual responses to antibiotics may vary, and the selection of an antibiotic should be based on diverse factors, including the specific infection being treated, the patient's health, and potential side effects.

PIM1is involved in critical cellular processes, playing a key role in the regulation of the cell cycle, apoptosis, transcriptional activation, and broader signal transduction pathways . The exploration of PIM1inhibitors, such as small molecules or antibodies, represents a promising avenue in cancer research for developing novel treatment strategiess. Its significance in oncogenic signaling has led to extensive research on PIM1 as a target in cancer studies. Docking studies have revealed a robust interaction between hypericin and PIM1, suggesting a strong binding affinity (-12.5 kcal/mol). This research aims to explore the molecular dynamics of the hypericin-PIM1 interaction, identifying potential binding sites and elucidating the impact on PIM1-mediated cellular processes, such as cell cycle regulation and apoptosis. The findings may contribute valuable insights into developing hypericin-based therapies targeting PIM1, paving the way for novel and effective strategies in cancer research.

Heat Shock Proteins play a crucial role in maintaining cellular integrity during thermal stress conditions, acting as chaperones and participating in the regulation of cellular responses. The focus was to contribute valuable insights into the potential role of hypericin in modulating these heat shock proteins and its implications for anti-tumoral properties. This study employs computational methods, specifically molecular docking, to investigate the potential biological interactions between the chaperone proteins HSP90 and HSC70 and Hypericin, a natural compound recognized for its anti-tumor properties. Despite the limited existing studies in this domain, this research aims to uncover structural insights into the binding mechanisms between Hypericin and these heat shock proteins. In the docking assessments, hypericin demonstrated notable binding energy results, exhibiting a binding energy of -10.5 kcal/mol with Heat Shock Cognate 71 kDa protein and -11.2 kcal/mol with Heat Shock Protein HSP90-alpha.

BACE1 is involved in the production of beta-amyloid peptides, and inhibiting its activity is a potential therapeutic strategy for managing Alzheimer's disease, as excessive beta-amyloid accumulation is a characteristic feature of the disease.Computational results suggest that hypericin has the potential to act as an inhibitor of BACE1. The Molecular Docking results indicate a high binding affinity between hypericin and BACE1, with a notable binding energy score of -10.3 kcal/mol. Additionally, the formation of various chemical bonds, including hydrogen bonds and hydrophobic bonds, further supports the idea that hypericin may effectively interact with the active site of BACE1. It's important to note that while the in silico Molecular Docking results are promising, further in vitro and in vivo studies would be necessary to validate and better understand the inhibitory potential of hypericin against BACE1. Additionally, the practical application of hypericin as a BACE1 inhibitor in a therapeutic context would require careful consideration of factors such as bioavailability, safety, and efficacy.

The assessment of Histone deacetylases in conjunction with Curcumin, conducted through the Mcule Database employing the Autodock Vina algorithm, involves an examination of molecular interactions. This analysis includes the calculation of binding energies, revealing the strength and stability of the interactions between Curcumin and various Histone deacetylase targets. The comparison encompasses diverse aspects such as binding energies, specific binding sites, interactions across different targets, structural details, and potential implications for biological activity. The results imply that Curcumin shows heightened affinity for Histone deacetylase 4 in comparison to other investigated histone deacetylases.

Nitrates can cause severe ecological imbalances in aquatic ecosystems, with considerable consequences for human health. Therefore, monitoring this inorganic form of nitrogen becomes essential for any water quality management structure. This research aimed at developing a novel Nitrate Portable Measurement System (NPMS) for monitoring nitrate concentrations in water samples. NPMS is a reagent-free ultraviolet system developed using low-cost electronic components. Its operation principle is based on Beer-Lambert law for measuring Nitrate concentrations in water samples through light absorption in the spectral range 295-315 nm. The system is equipped with ready to use ultraviolet sensor, Light Emission Diode (LED), op-amp, microcontroller, liquid crystal display, quartz cuvette, temperature sensor, and battery. All the components are assembled in a 3D-printed enclosure box which allows a very compact self-contained equipment, with high portability, enabling field and near real time measurements. The proposed methodology and the developed instrument were used to analyse multiple nitrate standard solutions. The performance was evaluated in comparison with the Nicolet Evolution 300, a classical UV-Vis spectrophotometer. The results demonstrate a strong correlation between the retrieved measurements by both instruments within the investigated spectral band and for concentrations above 5 mg NO3- /l.

This study presents a strategic approach to developing applications focused on implementing Large Language Models using the Langchain framework in Python. Three language models are highlighted: GPT-3.5 (turbo mode), LLaMA 2, and Vicuna 7B, each with their distinctive features and capabilities. The methodology used is described in detail, including data extraction from medical reports using zero-shot prompting data extraction techniques, interaction with language models, and structured storage of results. The performance of the models in data extraction is evaluated, presenting metrics such as precision, recall, and F1 score. The results demonstrate high model capability in extracting information, although areas for improvement are identified, particularly in data extraction precision. In conclusion, the efficacy of the models in extracting information from medical histories is not considerably acknowledged, with an emphasis on the importance of improving precision and increasing the volume of trained data for future research in healthcare digitalization.

Polydatin, a polyphenolic compound sourced from various natural origins, has garnered attention due to its potential anti-tumor properties and low toxicity. This research utilized Molecular Docking methods to investigate the molecular interactions between Polydatin and the Crystal Structure of Human UDP-glucuronic acid decarboxylase (UXS1), aiming to uncover the mechanisms contributing to its anti-tumor effects. The study revealed a substantial binding energy value of approximately -10 kcal/mol for the Polydatin-UXS1 interaction, indicating a robust and favorable binding. This suggests that Polydatin holds significant promise in cancer research, offering insights into its ability to interact with and potentially modulate the activity of UXS1. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of polydatin ( or piceid). From these results, the parameters for polydatin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile.These findings position Polydatin as a compelling candidate for further exploration in cancer research, highlighting both its efficacy and safety considerations.

We are going to demonstrate the origin of dark energy, using a Hardwire similarity, a test that is carried out in terrestrial seismic with vibroseis in the search for gas and oil. In the first instance, we are going to analyse the mathematical function of Dirac's delta and compare it with the detonation of an explosive that is carried out in the search for gas and oil. Let's understand that in both cases a frequency spectrum is produced. We will also explain the meaning of a non-causal, zero-phase system; a causal system, of minimum phase, in order to determine the mathematical behaviour that corresponds to the Big Bang. Next, following the line of seismic, we will analyse a Hardwire Similarity to demonstrate that a vibroseis source, which generates a sweep, produces, in addition to the ideal sweep of fundamental frequencies, spurious harmonic frequencies and additional noise. We will show that this additional energy generated by the spurious harmonic frequencies and additional noise adds to the energy of the fundamental frequency sweep in analogy as dark energy does.

Talking about sustainable development refers mainly to the environmental sphere, but the concept is much broader and also takes into account the social and economic conditions. The concept of sustainability, in this sense, is linked to the compatibility between the development of economic activities, the related social phenomena, and the protection of the environment. Therefore, the ability to balance social, economic and environmental sustainability is the very meaning of the concept of sustainable development. Firms that choose to develop policies and strategies to enhance and pursue sustainable development in the medium to long term have the burden of having to quantitatively document the improvements in production processes with the aim of sustainable development. As a result, one of the biggest challenges for European industry is to introduce sustainability principles into business models leading to competitive advantage. This is particularly important in raw material and energy intensive manufacturing sectors such as the ceramic industry. The present state of knowledge lacks a comprehensive operational tool for industry to support decision-making processes geared towards sustainability. In the ceramic sector, the economic and social dimensions of the product and processes have not yet been given sufficient importance. Moreover, the traditional research on industrial districts lacks an analysis of the relations between firms and the territory with a view to sustainability. Finally, the attention of scholars in the field of economic and social sustainability, has not yet turned to the analysis of the Sassuolo district. Therefore, in this paper we introduce the Life Cycle Sustainability Assessment (LCSA), as a method that can be a suitable tool to fill this gap, because through a mathematical model it is possible to obtain the information useful for decision makers to integrate the principles of sustainability both at the microeconomic level in enterprises, and at the meso-economic level for the definition of economic policies and territorial governance. Environmental and socio-economic analysis was performed from the extraction of raw materials to the packaging of the product on different product categories manufactured by the Italian ceramic industries of the Sassuolo district (northern Italy). For the first time the LCSA model, usually applied to unitary processes, is extended to the economic and industrial activities of the entire district, extending the prospect of investigation from the enterprise and its value chain to the integrated network of district enterprises.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

Variable-Angle Tow (VAT) laminates can improve straight fiber composites mechanical properties thanks to the application of curvilinear fibers. This characteristic allows to achieve ambitious objectives for design and performance purposes. Nevertheless, the wider design space and the higher number of parameters result in a more complex structural problem. Among the various approaches that have been used for VATs study, Carrera’s Unified Formulation (CUF) allows to obtain multiple theories within the same framework, guaranteeing a good compromise between the results accuracy and the computational cost. In this article, the linear buckling behavior of VAT laminates is analyzed through the extension of CUF 2D plate models within the Reissner’s Mixed Variational Theorem (RMVT). Results show that RMVT can better approximate the prebuckling non-uniform stress field of the plate when compared to standard approaches, thus improving the prediction of the linear buckling loads of VAT composites.

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

Pregnant women (PW) are at a higher risk of diseases and hospitalization from viral respiratory infections, specially influenza, due to cardiopulmonary and immunological changes. This study assessed the impact of viral respiratory infections on PW hospitalized with severe acute respiratory infection (SARI). It´s a cross-sectional study with 42 PW and 85 non-pregnant women (NPW) admitted with SARI to two tertiary hospital between January 2015 and December 2019. The rate of virus prevalence, SARI hospitalization, length of hospital stay, oxygen supplementation, intensive care unit (ICU) admission, and death were comparable between PW and NPW. Multivariate analysis showed that PW had a higher rate of viral SARI hospitalizations (OR = 2.37; 95% CI =1.02 - 5.48) compared to NPW, with influenza virus being the most prevalent (aOR =7.58; 95% CI =1.53 - 37.66). Length of hospital stay (aOR = 0.83; 95% CI = 0.73 – 0.95) and admission to the ICU (aOR=0.028; 95% CI=0.004 - 0.25) were lower in PW compared to hospitalized NPW. Respiratory viruses had a greater impact on the frequency of SARI in the group of PW. Although PW had a higher rate of influenza SARI, they had a better outcome than NPW due to the treatment they received.

This study investigates the potential of natural compounds against HIV-1 protease, a critical enzyme in the replication cycle of human immunodeficiency virus type 1 (HIV-1). HIV-1 protease is essential for cleaving large precursor proteins into smaller functional proteins necessary for viral maturation and infectivity. Protease inhibitors, specifically targeting HIV-1 protease, effectively suppress viral replication, aiding in the management of HIV infection. Using the SWISS DOCK Server, several natural compounds were investigated for their potential as inhibitors of HIV-1 protease. Docking results revealed that Amentoflavone showed excellent binding affinity with high Estimated ΔG values, suggesting its potential as an inhibitor of HIV-1 protease. Additionally, Amentoflavone exhibited similar promising results when tested against Roussarcoma virus protease. These findings indicate the potential of Amentoflavone as a natural compound against HIV and warrant further investigation into its therapeutic applications.

This study delves into the realm of potential therapeutics for breast cancer by conducting a comprehensive docking simulation and virtual screening analysis using Autodock Vina Algorithm. The focus based on the human epidermal growth factor receptor 2 (HER2), a key protein associated with various cancers, particularly in the context of breast cancer.The results reveal compelling insights into the binding interactions of several natural compounds and drugs with HER2. Notably, Acebilustat, Bemcentinib, and Amentoflavone exhibit outstanding binding energies, averaging around -10 kcal/mol, suggesting strong and favorable interactions with the HER2 target.These encouraging findings not only emphasize the potential biological significance of these compounds but also hint at their potential usefulness in fighting breast cancer.Their promising binding affinities with HER2 position them as potential candidates for further investigation and development as therapeutic agents against breast cancer.

Neisseria gonorrhoeae is a bacterium that causes the sexually transmitted infection gonorrhea. This study employed molecular docking simulations to investigate potential interactions between natural molecules and the Fe(3+) ions import ATP-binding protein fbpC in Neisseria gonorrhoeae FA 1090. Among the screened molecules, Hypericin exhibited a remarkable binding energy of approximately -13.2 kcal/mol, indicating a robust and favorable binding affinity with the target protein. This promising outcome suggests that Hypericin could serve as a potential candidate for further exploration as a therapeutic agent against Neisseria gonorrhoeae infections. However, it is imperative to emphasize that these in silico findings necessitate experimental validation through in vitro and in vivo studies to ascertain the actual efficacy and safety of Hypericin as a treatment option.

The issue of antibiotic resistance represents a significant threat that extends beyond human health, encompassing animal welfare and the sustainability of the natural environment. The inappropriate use of antibiotics, poor sanitation and inadequate control measures, have contributed to the emergence of drug-resistant bacteria, which can spread at the human-animal-environment interface. The documented presence of antimicrobials in agriculture, veterinary medicine and human medicine has convinced all stakeholders of the need to contribute to the development of a "One Health" approach, which recognises the interrelationships between animals, humans and their environment and the need to adopt a common strategy encompassing these sectors to limit the spread of antimicrobial resistance (AMR). Although a number of countries have implemented integrated surveillance systems to monitor antibiotic use and antimicrobial resistance, available data suggest that the use of antibiotics in humans, animals and the environment is increasing worldwide. Consequently, the emergence of antibiotic-resistant pathogens is becoming a recurring concern. This review provides a comprehensive overview of the measures that are necessary to be taken and implemented in order to guarantee global health security.

Introduction: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTC), papillary thyroid carcinoma (PTC) is the most common. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis, in order to obtain a personalized and more effective treatment of patients. Aims: This study aims to evaluated 1) miRNAs expression in a series of DTC, and the association with the presence of selected genetic mutations, in order to improve diagnosis and predict biologic behavior of DTC/PTC. 2) the reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. Material and methods: This series includes 176 samples (98 cytology samples and 78 formalin-fixed paraffin embedded (FFPE) tissues) obtained from 106 patients submitted to surgery, being 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and the results were analyzed using the 2- ΔΔCT method, using miR16 as an endogenous control. The discriminative ability of miRNAs expression regarding PTC diagnosis was evaluated using the area under the Receiver Operating Characteristic Curve (AUC). The association of miRNAs expression, clinicopatological features and genetic alterations (BRAF, RAS and TERTp) was evaluated in PTCs. Results/Discussion: All the analyzed miRNAs showed a tendency to be over expressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant than in benign tumors. In histology, corresponding discriminative abilities regarding PTC diagnosis were: miR-146b (AUC0.94, 95%CI 0.87-1), miR-221 (AUC0.79, 95%CI 0.68-0.9), miR-222 (AUC0.76, 95%CI 0.63-0.89) and miR-15a (AUC0.85, 95%CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); mi-R221 se=68.4, sp=90; miR222 se=73, sp=70, and mi-R15a se=72, sp=80. MicroRNAs were associated with aggressive clinicopathological features and tumor progression in PTCs (p &lt; 0.05), particularly for miR-222. Our data reveals a significant association between higher expression levels of miR-146b, miR-221 and miR-222, with the presence of BRAF mutation (p&lt;0.001), and miR-146b (p=0.016) and miR-221 (p=0.010) with the presence of RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Although this study has a relatively small sample size, over expression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs showed a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations results could be useful for an accurate diagnosis of DTCs/PTCs in FNAC.

Background: To compare photodynamic therapy 41 and the use of probiotics in reducing halitosis assessed through gas chromatography and microbiome analysis. Methods: Participants aged from 18 to 25 years, showing sulfide (SH2) ≥ 112 ppb on gas chromatography, were selected. They were divided into 4 treatment groups: Group 1 - Tongue Scraping; Group 2- Antimicrobial Photodynamic Therapy (aPDT); Group 3- Probiotics; Group 4- Antimicrobial Photodynamic Therapy (aPDT) and Probiotics. The halimetry process was performed before, immediately after the treatments, 7 days, 14 days and 30 days after the initial collection. The collections for later microbiological analysis were made along with the halimetry, for the microbiome analysis. Results: Treatment with aPDT or probiotics under these experimental conditions was not able to change the bacteria present in the biofilm of the tongue. Conclusions: More research is needed to know the behavior of the oral microbiome in the presence of halitosis and the effectiveness of new treatments.

: Crohn’s disease (CD) is a multifactorial chronic disorder that involves a combination of factors as genetic, immune response and gut microbiota. Actually, the therapy comprises salicylates, immunosuppressive agents, corticosteroids, biologic drugs. International guidelines don’t recommend the use of antibiotics except for septic complications of CD patients. The increased evidence of the implication of gut bacteria in this chronic disease support the rationale for using antibiotics as primary treatment of active CD. In the last decades several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E.coli) species and Mycobacterium avium paratubercolosis (MAP), aroused the interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment in CD patients but randomized trials of antibiotic treatments against E.coli and MAP did not show prolonged benefits, and only generated conflicting results so much so that several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course and the outcome measures. In this article we attempted to provide an overview and update of the trials on antibiotic treatment in active CD patients taking into account the role of pathogens, the mechanism by which the different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also tried to draw new lines for future studies to use antibiotics to treat active CD patients

This work offers a new log generalized odd log-logistic exponential regression model for analyzing weekly dengue fever cases in 2022 with a location-systematic component. To achieve this, a data set of 49 observations of dengue fever cases in the Federal District of Brazil is employed. A review of the mathematical properties of the generalized odd log-logistic exponential distribution is provided, the maximum likelihood method is used to estimate the parameters, and, through Monte Carlo simulations, the accuracy of the estimators is investigated. The model's fit is assessed using global influence metrics and residual analysis. For the time scenario studied, the proposed regression identified factors that have an impact on dengue fever cases, which may contribute to improve disease control. Finally, several interpretations are addressed, and a discussion presents results that aid in better understanding the data set and future research on different data.

The background of this research is the environmental sustainability assessments in the aviation ecosystem, particularly concerning airports, are getting significant attention from the industry, regulators, and researchers. A standardized and comprehensive approach is essential for uniformly addressing the global impacts of these assessments across the industry. The main objective of this study is to develop a unique framework that encompasses the requirements of aviation regulators as well as industry and academic metrics, aiming for a standardized approach to environmental sustainability assessments at airports. The methodology used the Sum of Ranking Method to evaluate each environmental indicator precisely. It was applied to five airports globally, providing a diverse testing ground to assess the proposed metrics’ applicability and effectiveness and validate the framework. The results showed that applying the framework across these varied airport environments demonstrated its viability and effectiveness, indicating that it can be successfully applied to different airport realities. The conclusion shows that the developed framework can be successfully applied globally, suggesting that it can be a valid method for international adoption in environmental airport sustainability analysis, offering a standardized approach that could be accepted and utilized worldwide.

In the Mediterranean Sea, there are two critical issues affecting marine benthic biocenosis: the sedimentation process and the increasing trend in marine biodiversity loss. These processes are very marked along the western side of Calabria coastline where siltation is one of the main reasons for the regression of Posidonia beds in the regional coastal waters. This research aims to investigate the relationships between the geomorphological features of the debris source areas, represented by fluvial basins, and the distribution of Posidonia meadows. So, a geomorphological study of the Tyrrhenian fluvial basins with area greater than 200 km2 and its correlation with the mapping of the meadows in the Calabria Tyrrhenian waters was carried out. Furthermore, in order to assess the increased level of burial in a Posidonia oceanica meadow and its health state over time, a program of Posidonia monitoring was undertaken between 2000 and 2010, in a test area located in the Marine Regional Park of Isca (Calabria, Southern Italy). The results of this survey highlighted that, at the beginning of the study period, for a silting rate of 4 - 5 cm/year, the meadow suffered a reduction of its photosynthetic ratio with a rate of mortality of 50%. In the following years, the siltation rate reach 12 cm/year in 2010 and the meadow began to disappear. Therefore, the marine pollution by sedimentation represents a serious factor for the regression of Posidonia oceanica meadows, enhancing the risk of a gradual loss in marine biodiversity.

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities in de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have changed the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road towards a personalized treatment for de novo mHSPC is still long considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as predictive biomarker requires further validation, as well as it remains to ascertain how the genomic alterations detected in mHSPC, that are considered predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

An explanation of the origin of dark matter is suggested in this work. The argument is based on symmetry considerations about the concept of mass. In the Wigner's view, the rest mass and the spin of a free elementary particle in flat space-time are the two invariants that characterize the associated unitary irreducible representation of the Poincar\'e group. The Poincar\'e group has two and only two deformations with maximal symmetry. They describe respectively the de Sitter (dS) and Anti de Sitter (AdS) kinematic symmetries. Analogously to their shared flat space-time limit, two invariants, spin and energy scale for de Sitter and rest energy for Anti de Sitter, characterize the unitary irreducible representation associated with dS and AdS elementary systems. While the dS energy scale is a simple deformation of the Poincaré rest energy and so has a purely mass nature, AdS rest energy is the sum of a purely mass component and a kind of zero-point energy derived from the curvature. An analysis based on recent estimates on the chemical freeze-out temperature marking in Early Universe the phase transition quark-gluon plasma epoch to the hadron epoch supports the guess that dark matter energy might originate from an effective AdS curvature energy.

Proteins play a pivotal role in supporting athletes by promoting muscle hypertrophy and minimizing protein catabolism during exercise. They stimulate muscle protein synthesis, aiding in the repair of exercise-induced muscle damage and serving as an energy source, particularly for post-exercise glycogen replenishment. In individuals with phenylketonuria (PKU), for whom protein intake is limited to essential phenylalanine (Phe), supplementation with Phe-free amino acids or glycomacropeptides is necessary. Tailored for macronutrient and micronutrient content, these protein substitutes fulfill most protein requirements, but lack Phe, unlike dietary sources of protein. Protein requirements for athletes with PKU exceed general recommendations due to limited availability in supplements and potential catabolism mitigation. Various factors influence tolerated dietary Phe in PKU, including protein substitute quantity, distribution, pharmacological treatment, age, growth rate, pregnancy, catabolic states, and physical activity. While general protein requirements for PKU surpass those of the general population, adherence to supplement regimens is crucial for athletes and patients with PKU. Strategically timed protein substitutes enhance muscle protein synthesis, body composition, and sports performance within safety limits. Individualized intake is essential for optimal outcomes, as proteins have a multifaceted role in optimizing athletic performance and addressing challenges in PKU.

Based on the elasticity theory, this paper deals with the static analysis of a cracked double beam system in presence of a Winkler medium. The double-beam system is also supposed to be constrained at both ends by elastically flexible springs, with transverse and rotational stiffness. Using a variational formulation, the static governing equations are derived and solved by using analytical and numerical approaches. In the first approach, the closed-form solutions for the displacements functions are obtained based on the Euler-Bernoulli beam theory. In the second approach, the Cell-Discretization Method (CDM) is performed, according to which the two beams are reduced to a set of rigid bars linked together by means of elastic constraints, where the bending stiffness of the bars is concentrated. The resulting stiffness matrix is easily deduced, and the governing equations of the static problem can be immediately solved. A comparative analysis is performed in order to verify the accuracy and validity of the proposed method. This study focuses on the effect of various parameters including the crack depth and position, boundary conditions, elastic medium and slenderness. The validity of the proposed analysis is confirmed by comparing the present results with those obtained from the other approach. In particular, the results obtained by closed-form solution and Cell-discretization method (CDM) are compared by Finite element method (FEM). Accuracy of the results has been evaluated by making comparisons with the results in literature and reported in bibliography. It is demonstrated that the proposed algorithm provides a simple and powerful tool in dealing with the static analysis of a double-beam system. Finally, some concluding remarks are made.

Oral mucositis is most frequently a toxic effect of chemotherapeutic and/or radiotherapeutic treatment, resulting from complex multifaceted biological events involving DNA damage. The clinical manifestations have a negative impact on the life quality of cancer patients. Preventive measures and curative treatment of mucositis are still not well established. The glycine has anti-inflammatory, immunomodulatory and cytoprotective actions, being a potential therapeutic in mucositis. The objective was to evaluate the effects of glycine on the expression of collagen and growth factors, platelet and epidermal in oral mucositis. The mucositis of which was induced by the protocol of Sonis. 40 hamsters were used, divided into two groups: Group I- control; Group II- supplemented with 5% intraperitoneal glycine, 2,0 mg/g diluted in hepes. Histopathological sections were used to perform the immune-histochemical method, the evaluation collagen expression and the growth factors: EGF and PDGF. It was observed that the group supplemented with glycine higher amounts of collagen expression and predominance type of collagen I. The glycine group presented lower immunoexpression of the growth factors, EGF and PDGF. The group supplemented with glycine showed a marked healing process of the oral mucosite, demonstrated by the predominance of collagen type I and reduction of growth factors, EGF and PDGF.

Background: Colorectal cancer (CRC) can significantly impact mental health, increasing suicide risk. Variables such as pain and threat perception may be crucial. This study aims to identify predictors of suicide risk in individuals with CRC. Methods: A total of 71 participants (76.06% men) aged 27 to 88 years (M = 65.18, SD = 12.02) were assessed using the SF-36 for pain, the Brief Illness Perception Questionnaire (B-IPQ) for threat perception, the Hospital Anxiety and Depression Scale (HADS) for emotional distress, and the Plutchik suicide risk scale for suicide risk. Descriptive, comparative, and correlational analyses were performed, followed by a linear regression analysis. Results: Nearly 20% of participants exhibited high suicide risk. There was a moderate to high association between suicide risk and the perception of threat, pain, and emotional distress. The linear regression model explained 39% of the variance in suicide risk, with threat perception, pain, and emotional distress as significant predictors. Conclusions: These results indicate the need for multidisciplinary care for individuals with CRC, including emotional support from health psychologists, and holistic, human-centered care from nursing and medical professionals. Future research is necessary to further explore these relationships and improve patient care strategies.

Objective: The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on comorbid symptoms of depression, anxiety, and fatigue in migraine patients resistant to traditional prophylaxis. Methods: The study was an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis treated with anti-CGRP/R mAbs for 3 months. Results: 77 patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44% respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥ 50% of headache frequency. The two groups were highly homogeneous for investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms were reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. Conclusion: anti-CGRP/R antibodies improve pain together with affection, fatigue, and sensory sensitization in migraine patients.

Prolonged fatigue is associated with non-pathological causes, and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve® Response) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue Severity Scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stressed conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months supplementation in healthy subjects with mild prolonged fatigue.

Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of ASCs secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.

Inflammation is a vital aspect of the body's immune response, appearing either as an acute reaction that swiftly develops (e.g., after injury or during an infection) or as a chronic condition that persists over a prolonged period, often linked with autoimmune disorders or cancer. This study introduces potential TNF-alpha inhibitors investigated by Molecular Docking investigation. They are Dactolisib with a binding energy of -10.1 kcal/mol, Nilotinib with -9.6 kcal/mol, Eltrombopag with -9.7 kcal/mol, Radotinib with -9.6 kcal/mol, and Nilotinib again with -9.7 kcal/mol. Additionally, Hypericin exhibited a notable binding energy of -9.9 kcal/mol, suggesting its potential as a natural TNF-alpha inhibitor. While these computational results are preliminary, they provide a foundation for further biological studies to confirm their efficacy. The significance of these findings extends to the scientific community, offering potential applications in the field of inflammatory diseases.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

Abstract This study focuses on the toxicity assessment of various flavonoids, with particular emphasis on Hesperidin. Among the investigated compounds, Hesperidin exhibits notable potential and low toxicity in both short and long-term evaluations. The toxicity parameters for Hesperidin include a low Max. Tolerated Dose (Human) (0.525 log mg/kg/day), indicative of its minimal potential harm to humans. Additionally, its Oral Rat Acute Toxicity (LD50) (2.506 mol/kg) suggests a relatively low acute toxicity level. The Oral Rat Chronic Toxicity (LOAEL) (3.167 log mg/kg_bw/day) signifies a higher dose threshold for observing adverse effects over the long term. Furthermore, Hesperidin demonstrates low Minnow Toxicity (7.131 log mM), suggesting minimal impact on aquatic organisms. Overall, this comprehensive assessment positions Hesperidin as a promising flavonoid with favorable properties and minimal toxicity.

Molecular docking, a computational method predicting how molecules bind to target proteins, is employed in this study to explore Polydatin's interactions with Ras-related protein Rab (Rab) proteins using the Mcule Database. This database validates the docking results and offers insights into the pharmacological properties of Polydatin. Notably, specific Rab proteins like Rab-5A, HRas, and Rab-18 exhibit robust interactions with Polydatin, indicated by favorable binding energies.These findings illuminate the potential roles of Polydatin in therapeutic and biological contexts, emphasizing its interaction with Rab proteins. The Mcule Database enhances the credibility of the study, providing additional perspectives on Polydatin's applications. The observed interactions, particularly with key proteins like HRas, present a promising avenue for modulating cellular signaling pathways. This modulation holds therapeutic potential, potentially addressing conditions associated with pathway overactivity, including specific cancer types.

Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.

This research concerns in to understand the link between urban heat and cool island, the Local Climatic Zones (LCZ) and atmospheric systems during the winter season in the city of Balneário Camboriú, Southern Brazil. To collect meteorological data on urban environmental, 11 permanent points in the Balneário Camboriú metropolitan region were installed. To understand the atmos-pheric systems operating in the region, a synoptic analysis of the dates was performed, and then, the LCZs map created for the city in World Urban Database and Acess Portal Tools was used to cor-relate the magnitudes of the heat and cool islands found in Balneário Camboriú in the winter period. The results indicate that the increasing verticalization with the construction of skyscrapers in Balneário Camboriú has a significant influence on local conditions for the occurrence of heat and cold islands. The findings indicate that LCZs with sparsely distributed buildings (LCZs 6, 8 and 9) and LCZs with dense vegetation (LCZ A) have lower intensity magnitudes of heat and cool con-ditions. The biggest magnitudes of heat and cool islands were reported in LCZs 1 and 3 during the timeframe. The synoptic analysis supports earlier researches that points to atmospheric stability (Anticyclonic domain) as a favorable atmospheric setting for the emergence of urban hear and coolness islands.

Sporotrichosis’ clinical manifestations, lesions in the cutaneous or subcutaneous tissues, it is caused by dimorphic fungi of the Sporothrix complex, is a cosmopolitan mycosis that affects humans and animals. This study aimed to identify prevalent species in Minas Gerais, Brazil, and characterize virulence profiles and antifungal susceptibility associated with Sporothrix isolates. Isolates were identified using macro and micro-morphological traits as well molecular biology techniques. Antifungal susceptibility was determined using the Minimal Inhibitory Concentration test, while, virulence factors such as growth at different temperatures, biofilm formation, melanin production, and urease activity were assessed. Our findings revealed S. brasiliensis as a predominant species isolated. Urease activity was a crucial factor associated with growth at 50°C in S. brasiliensis isolates, highlighting their high thermotolerance. Furthermore, strains isolated from humans produced a more robust biofilm compare to those from felines. Strains of S. brasiliensis isolated from Felis catus exhibited faster melanin production, decreased susceptible to antifungal agents tested, and superior growth capacity at 50°C to strains isolated from humans. Therefore, our study highlights the prevalence of S. brasiliensis causing sporotrichosis in both human and felines. However, it underscores the circulation of different strains, with varying levels of virulence and susceptibility to antifungal agents.

There is a growing trend among consumers to seek out natural foods and products with natural ingredients. This shift in consumer preferences had a direct impact on both food and pharmaceutical industries, leading to a focus of scientific research and commercial efforts to meet these new demands. The aim of this work is to review recent available scientific data on foods of interest, such as artichoke, gooseberry, and polygonoideae plants, as well as olive oil and red raspberries. Interestingly, the urgency of solutions to the climate change emergency has brought new attention to by-products of grapevine bunch stem and cane, which have been found to contain bioactive compounds with potential health benefits. There is a pressing need for a faster process of translating scientific knowledge from the laboratory to real-world applications, especially in the face of the increasing societal burden associated to non-communicable diseases (NCDs), environmental crises, the post-pandemic world, and ongoing violent conflicts around the world.

Patients with COVID-19 have coagulation and platelet disorders, with platelet’s alterations and thrombocytopenia representing negative prognostic parameters, being associated with severe forms of the disease, and increase lethality. Methods: Aim of this study was to study expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation Results: a total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19 +), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS CoV-2 (-) negative lungs (COVID-19 -), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1 positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of dead patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocytes over-expression in the lung. Conclusions: microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

Calcium sulphate (CS) is currently used as a bioabsorbable, completely synthetic and sterile material in the management of infected tissues and dead spaces (DS) mainly resulting from surgical procedures. Residual DS in the postoperative, may create an environment where hematomas fill up and bacteria can proliferate, leading to a high incidence of postoperative infections. Considering the available reviews in the literature, CS has been mainly studied in orthopedic surgery mostly giving brilliant results and low complication rates. Nowadays, orthopedists avail it in the form of pearls both as a bone void filler and as an “off-label” delivery agent for antibiotics in arthroplasty, chronic osteomyelitis and open fractures, paving the way of its application in many other contexts given its natural dis-position to biodegradation. In the last years, CS beads have been gaining ground in the general, vascular and endocrinological surgical specialties. Despite its clear potential and the increasing number of scientific evidences on the safety and effectiveness of CS application in the prophylaxis and treatment of infections, there are not many studies reporting on its application in fields other than orthopedics, with a substantial paucity in plastic and reconstructive surgery literature. This is some-how surprising, since reconstructive surgery often deals with complex wounds secondary to bone and soft tissue exposure, suture dehiscence, trauma, and surgical site infections. As far as we know this is the first updated systematic review assessing the state of the art, indications and new perspectives on the application of CS beads in plastic and reconstructive surgery.

Corneal biomechanics is a hot topic in ophthalmology. The biomechanical properties of the cornea (BMPs) have important implications in the management and diagnosis of corneal diseases such as ectasia and keratoconus. In addition, the characterization of BMPs is crucial to model the predictability of a corneal surgery intervention, the outcomes of refractive surgery or follow-up of corneal diseases. The biomechanical behavior of the cornea is governed by viscoelastic properties that allow, among other structural implications, the damping of excess of intraocular pressure and reduce damage to the optic nerve. Currently, the most versatile and complete methods to measure corneal viscoelasticity are based on air-puff corneal applanation. However, those methods lack the ability to directly measure corneal viscosity. The aim of this work is to propose a new methodology based on the analysis of corneal air-puff measurements through the Standard Linear Solid model (SLSM) to provide analytical expressions to separately calculate the elastic and time-dependent (corneal retardation time and viscosity) properties. The results shown the mean values of elasticity (E), viscosity (Ƞ) and corneal retardation time (τ) in a sample of 200 young and healthy subjects. The influence of elasticity and viscosity on viscoelasticity, high-order corneal aberrations and optical transparency is investigated. Finally, the SLSM fed back from experimental E and Ƞ values was employed to compare the creep-relaxation response between normal, an ocular hypertension patient and Ortho-K user.

The progressive reappearance of the Zika virus (ZIKV) infection since October 2013 and its circulation in >70 countries and territories (from French Polynesia to Brazil and other countries in the Americas, with sporadic spread in Europe and the East) has long been reported as a global public health emergency. ZIKV is a virus transmitted by arthropods (arboviruses), mainly by Aedes mosquitoes. ZIKV can also be transmitted to humans through mechanisms other than vector infection such as sexual intercourse, blood transfusions, mother-to-child transmission. The latter mode of transmission can give rise to a severe clinical form called Congenital Zika Syndrome (CZS) which can result in spontaneous abortion or serious pathological alterations in the fetus such as microcephaly, neurological and orofacial anomalies. In this study, beside a succinct overview of the etiological, microbiological, epidemiological aspects and modes of transmission of Zika virus infection, we have focused our attention on the pathogenetic and histopathological aspects in pregnancy and the pathogenetic and molecular mechanisms that can determine microcephaly, and consequently the clinical alterations, typical of the fetus and newborns, in a subject affected by CZS.

As a form of protection, a nature park is often created to protect and valorise natural and cultural heritage in peripheral rural areas. However, in terms of multi-functionality, new nature parks are incorporated into traditional productive activities, such as recreational and tourist activities, which sometimes compromise sustainability. The research objective is to study the relationship between tourism and sustainability in the Nature Parks of “Sierra de Aracena y Picos de Aroche”, “Sierra Norte de Sevilla” and “Sierra de Hornachuelos” that makes up the Dehesas de Sierra Morena Biosphere Reserve in Andalusia, Spain. Therefore, selective interviews have been carried out with the stakeholders to establish their perception of sustainable tourism and the presence of dominant discourses. The main conclusions indicate (1) the presence of different dominant discourses on sustainability, namely the conservationist and mercantilist ones, with the prevalence of the economic dimension; (2) poor awareness and adaptation to the context of global change; and (3) the presence of competitive relationships that generate difficulties for the governance of sustainable tourism.

Diabetes mellitus is acknowledged as a significant contributor to severe complications. The present work has explorated the potential role amentoflavone as an aldose reductase inhibitor through Docking Simulations. From these results this compound has shown excellent results with this enzyme with a high binding energy of -11 kcal/mol. If amentoflavone,a natural biflavonoid, proves effective in inhibiting aldose reductase, it could hold therapeutic promise for managing diabetic complications. However, it's crucial to emphasize that while computational studies offer valuable insights, experimental validation is essential to confirm the actual inhibitory effects and to establish the safety and efficacy of amentoflavone for this purpose. Further research and clinical studies are warranted to fully understand and harness the potential therapeutic benefits of amentoflavone in the context of diabetes.

Climate change related increases in frequency and intensity of heatwaves affect viticulture, leading to losses in yield and grape quality. We assessed whether canopy architecture manipulation mitigates the effects of summer stress in a Mediterranean vineyard. Muscat of Alexandria grapevines were monitored during 2019-2020. Two canopy shoot positioning treatments were applied: Vertical shoot positioning (VSP); and Modulated shoot positioning (MSP), the west side upper foliage released to promote partial shoot leaning, shading the clusters. Clusters were sampled at pea size (PS), veraison (VER) and full maturation (FM). Measurements included rachis anatomy and hydraulic conductance, and aquaporins (AQP) and stress-related genes expression in cluster tissues. Results show significant seasonal and interannual differences in Kh and vascular anatomy. At VER, Krachis , Krachis+pedicels, and xylem diameter decreased but were unaffected by treatments. The Phloem/Xylem ratio was either increased (2019) or reduced (2020) in MSP, compared to VSP. Most AQP were down-regulated at FM in pedicels, and up-regulated at VER in pulp. A potential maturation shift in MSP was observed, confirmed by the up-regulation of several stress-related genes in all tissues. The study pinpoints the role of canopy architecture in berry water relations and stress response during ripening.

Here we will electrically-quantum model the neutron and proton as a three-phase alternating current electric generator, for this, we will use the theory of three-phase electric generators and vector or phasor diagrams. We will use this model to hypothesize how the quarks that form neutrons and protons with a combined mass of 10 MeV/c², can generate, through quarks-antiquarks-gluon interactions, a mass of 939.56 MeV/c² for the neutron and a mass of 938.27 MeV/c² for the proton. Using quantum mechanics and the theory of the generalization of the Boltzmann constant in curved space-time we will calculate the number of quarks-antiquarks-gluons and gravitons inside a neutron. We will also analyse βˉ decay using vector diagrams, we will calculate the tension of the string T₀ and the length of the string ℓs between quarks-antiquark and finally, we will model a black hole using a neutron equivalent model. In version 2 of this article, we will update the vector diagrams of the βˉ decay and theoretically calculate the energy of the W⁻ boson, the Z⁰ boson, and the Θ angle, Θ = arc cos (W⁻/Z⁰). We will demonstrate, through vector diagrams, that quarks-antiquarks-gluon interactions are the cause of the origin of the W⁻ boson and the Z⁰ boson. We will also demonstrate how the fine structure constant α originates. It is important to make clear, in future updates, we will describe the relationship that exists between the theory described in this paper and the Isospin theory, flavour and colour theory