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.

We used agar overlay assays to assess if 24 circulating and historical isolates of Neisseria mucosa could inhibit the growth of 28 circulating and historical isolates of N. gonorrhoeae. We found no evidence of inhibition by N. mucosa (n=24). Positive controls Streptococcus pneumoniae and Escherichia coli demonstrated a strong inhibitory effect against the growth of N. gonorrhoeae.

Antibiotic-sparing treatments are required to prevent the further emergence of anti-microbial resistance in Neisseria gonorrhoeae. Commensal Neisseria species have previously been found to inhibit the growth of pathogenic Neisseria species. For example, a previous study found that 3 out of 5 historical isolates of Neisseria mucosa could inhibit the growth of N. gonorrhoeae. In this study, we used agar overlay assays to assess if 24 circulating and historical isolates of Neisseria mucosa could inhibit the growth of 28 circulating and historical isolates of N. gonorrhoeae. Although pitting around each colony of N. mucosa created an optical illusion of decreased growth of N. gonorrhoeae, we found no evidence of inhibition (n=24). In contrast, positive controls of Streptococcus pneumoniae and Escherichia coli demonstrated a strong inhibitory effect against the growth of N. gonorrhoeae.

Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting in dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. This increasing detection of resistant gonococcal strains may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics, (2) development of new antibiotics and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this Superbug. This has lead the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

Chromosomal rearrangements in N. gonorrhoeae and N. meningitidis were studied with the determination of mobile elements and their role in rearrangements. The results of whole-genome sequencing and de novo genome assembly for 50 N. gonorrhoeae isolates collected in Russia were compared with 96 genomes of N. gonorrhoeae and 138 genomes of N. meningitidis from the databases. Rearrangement events with the determination of the coordinates of syntenic blocks were analyzed using the SibeliaZ software, the minimum number of events that allow one genome to pass into another was calculated using the DCJ-indel model using the UniMoG program. Population-level analysis revealed a stronger correlation between changes in the gene order and phylogenetic proximity for N. meningitidis in contrast to N. gonorrhoeae. Mobile elements were identified, including Correa elements, Spencer-Smith elements (in N. gonorrhoeae), Neisserial intergenic mosaic elements, IS elements of IS5, IS30, IS110, IS1595 groups, Nf1-Nf3 prophages, NgoФ1-NgoФ9 prophages, Mu-like prophages Pnm1, Pnm2, MuMenB (in N. meningitidis). More than 44% of the observed rearrangements most likely occurred with the participation of mobile elements, including prophages. No differences were found between the Russian and global N. gonorrhoeae population both in terms of rearrangement events and in the number of transposable elements in genomes.

Maximum likelihood estimation (MLE) is a popular method for parameter estimation in both applied probability and statistics but MLE cannot solve the problem of incomplete data or hidden data because it is impossible to maximize likelihood function from hidden data. Expectation maximum (EM) algorithm is a powerful mathematical tool for solving this problem if there is a relationship between hidden data and observed data. Such hinting relationship is specified by a mapping from hidden data to observed data or by a joint probability between hidden data and observed data. In other words, the relationship helps us know hidden data by surveying observed data. The essential ideology of EM is to maximize the expectation of likelihood function over observed data based on the hinting relationship instead of maximizing directly the likelihood function of hidden data. Pioneers in EM algorithm proved its convergence. As a result, EM algorithm produces parameter estimators as well as MLE does. This tutorial aims to provide explanations of EM algorithm in order to help researchers comprehend it. Moreover some improvements of EM algorithm are also proposed in the tutorial such as combination of EM and third-order convergence Newton-Raphson process, combination of EM and gradient descent method, and combination of EM and particle swarm optimization (PSO) algorithm.

Background: Bacteria can survive antibiotic exposure by mechanisms like tolerance without a shift in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone (CRO), azithromycin (AZM), and ciprofloxacin (CIP), in clinical isolates and WHO reference panel of N. gonorrhoeae and explored the prevalence between urogenital and anorectal infection sites. Methods: We examined 66 N. gonorrhoeae clinical isolates, evenly divided between anorectal and urogenital infection sites, using a modified tolerance disk (TD test) for three antibiotics. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disc for 20 hours of incubation (Step I), followed by the replacement of the antibiotic disc with a nutrient disc for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). Results: Four isolates were lost due to contamination. Of 62 clinical isolates, 7 exhibited tolerance to AZM, with 6 from anorectal and 1 from urogenital sites (p = 0.0496). Tolerance to CRO was observed in 11 isolates, which was significantly associated with the infection site, with 9 from the anorectum, and 2 from the urogenital site being tolerant (p = 0.02). Tolerance to CIP was found in 11 isolates, but was not significantly associated with the infection site. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO (World Health Organization) reference strains, with varying patterns of tolerance to CRO (n=8), CIP (n=2) and AZM (n=1). Conclusion: This study identified CRO, AZM, and CIP tolerance in clinical Neisseria gonorrhoeae isolates. Significant variations in tolerance proportions between anorectal and urogenital infection sites, particularly for CRO, were observed. Additionally, tolerance was detected in WHO reference strains.

Background: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV PrEP have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6-months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population. Methods: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals. Results: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals. Conclusions: We conclude that in high antimicrobial consumption populations, the association between antimicrobial consumption and resistance may be attenuated.

Although working memory (WM) is crucial for intellectual abilities, not much is known about its brain underpinnings, especially the structural connectivity. We used diffusion tensor imaging (DTI) to look across the whole brain for the white matter integrity correlates of the individual differences in the reading span (verbal WM capacity during reading) in healthy adults. Right-handed healthy native Russian speakers (N = 67) underwent DTI on a 3T Philips Ingenia scanner. Verbal WM was assessed with the Daneman-Carpenter reading span test (Russian version). Fractional anisotropy maps from each participant were entered into the group tract-based spatial statistics analysis with the reading span as a covariate; the results were TFCE-corrected. After taking into account effects of age, sex, education and handedness, reading span positively correlated with the white matter integrity in multiple sites: the body, the genu and the splenium of corpus callosum; bilateral corona radiata (anterior, posterior, and superior); bilateral superior longitudinal fasciculus; several tracts in the right hemisphere only, including the internal and external capsule; bilateral superior parietal and frontal white matter. Although the left hemisphere is central for verbal processing, we revealed the important role of the right hemisphere white matter for the verbal WM capacity. Our finding indicates that larger verbal working memory span may originate from additional processing resources of the right hemisphere.

Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the CDC recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic ,cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an ELISA and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.

Background: The resurgence of syphilis, primarily in MSM populations, has necessitated novel prophylactic strategies, such as the use of doxycycline post-exposure prophylaxis (doxy-PEP). However, the potential for increased doxycycline use to select for tetracycline resistance represents significant challenges in managing this sexually transmitted infection. This study aims to identify chromosomal mutations associated with tetracycline resistance in Spirochaetales to inform treatment strategies and surveillance measures.Methods: Whole genome sequences (WGS) from the Spirochaetales order, including 4,355 genomes, were analyzed for the presence of mutations in 16S rRNA and non-synonymous mutations in the rpsC and rpsJ genes. The study utilized WGS from GenBank® and sequence data from the PubMLST Treponema pallidum isolate collection. Genetic resistance to tetracycline was detected using a combination of BLASTN searches and gene-gene analysis. Results: A transition mutation TGA to TGG at positions 965-967 in the 16S rRNA gene was detected in 5.6% of Treponema spp. and 3.97% of Spirochaeta spp. genomes. The rpsJ gene exhibited a V57G amino acid substitution across a significant subset of Treponema spp. Notably, the V57K mutation was common in Spirochaeta spp. The rpsC gene had the H178Q mutation and was found to be present in the Spirochaetales bacterium.Conclusion: The identification of mutations associated with tetracycline resistance in Spirochaetales provides a foundation for the development of rapid molecular diagnostics and guides the clinical selection of antibiotics for syphilis treatment. This study underscores the complexity of antibiotic resistance mechanisms and the critical importance of surveillance in the era of antibiotic prophylaxis for STI management.

It is unclear how important it is to reduce fluoroquinolone consumption in the general population to prevent the spread of fluoroquinolone resistance in Neisseria gonorrhoeae (bystander selection). Methods We assessed bystander selection by using Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in N. gonorrhoeae was correlated with the prevalence of fluoroquinolone resistance in four other gram-negative species - Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Results Fluoroquinolone resistance in N. gonorrhoeae was positively associated with homologous resistance in all 4 species - A. baumanii. (ρ=0.61, P=0.0003, E. coli (ρ=0.67, P<0.0001), K. pneumoniae (ρ=0.52, P=0.0004) and P. aeruginosa (ρ=0.40, P=0.0206). Positive associations were also found between the national prevalence of fluoroquinolone resistance and fluoroquinolone consumption in the general population in the preceding year for 4 of the 5 species. Conclusions Gonococcal fluoroquinolone resistance can be productively viewed as being part of a syndemic of fluoroquinolone resistance. Strengthening antimicrobial stewardship programs may help retard the spread of fluoroquinolone resistance in N. gonorrhoeae.

Corrugated board is a composite material characterized by strong orthotropy in both the elastic and plastic phases. Additionally, due to its layered structure, which consists of alternately arranged flat and wavy layers of paper, its mechanics becomes complicated. Therefore, a precisely selected set of laboratory tests is needed to correctly identify all the necessary material parameters of cardboard. The work attempts to define a full set of laboratory tests in order to determine material parameters describing the linear-elastic, orthotropic behavior of cardboard and the basic parameters defining popular plasticity criteria, such as the asymmetric orthotropic Hoffman criterion. For this purpose, sensitivity analysis and numerical models of several selected basic laboratory tests were used. Since the aim of the work is to choose appropriate laboratory tests necessary to correctly determine the material parameters of corrugated board (not its individual layers), the numerical models do not contain detailed cardboard geometry, but only its homogenized representation in the form of the flat shell models. All numerical models are based on the nonlinear finite element method and constitutive modelling in the form of UMAT subroutines implemented in the ABAQUS software. Based on the analyses, appropriate measurements and laboratory tests were indicated that are most sensitive to the material parameters sought.

My innovative entropy measure, Ismail entropy, namely, (IE) is an ultimate generalization to numerous generalized entropies within the literature. The fractal dimension of IE is identified in this paper. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

Cucurbitacin phytonematicides consistently suppress population densities of plant nematodes, but have no effect against bacteria, fungi and insects. This study investigates the mechanism through which cucurbitacin phytonematicides consistently exert nematicidal properties on nematodes. Post 72-h exposure of second-stage juveniles (J2) of Meloidogyne enterolobii to geometric concentration of Nemafric-BL phytonematicide, J2 total proteins were measured using TruspecCHNS Macro. Total proteins versus phytonematicide exhibited a negative quadratic relation (R² = 0.97), with the minimum total proteins achieved at x = 4.9% phytonematicide. Beyond the minimum, total proteins increased gradually, depicting the existence of both isoprenylation (breakdown) and farnesylation (biosynthesis) of total proteins. In conclusion, cucurbitacins and nematode cuticles are both chemically structured, which provides the mechanism through which the test chemicals consistently decrease population densities of plant nematodes.

Kininogens are multidomain glycoproteins found in the blood of most vertebrates. They are important in the blood coagulation cascade pathways - in intrinsic pathway activation leading to thrombin generation partially independently from tissue factor dependent extrinsic pathway, connecting blood coagulation with the kallikrein-kinin system. Nothing is known about the shape on atomic level therefore the endeavor to obtain the good-quality spatial structure of kininogens is important for a better understanding of their role in disease and treatment. Application of cryo-EM is important for solving the spatial structure of kininogens, drawing new frontiers in understanding the function and opening new pathways for drug development.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

In the absence of a vaccine, current antibiotic-dependent efforts to reduce the prevalence of Neisseria gonorrhoeae in high prevalence populations have been shown to result in extremely high levels of antibiotic consumption. No randomized controlled trials have been conducted to validate this strategy and an important concern of this approach is that it may induce antimicrobial resistance. To contribute to this debate, we assessed if mass treatment in the related species, Neisseria meningitidis, was associated with the emergence of antimicrobial resistance. To this end, we conducted a historical review of the effect of mass meningococcal treatment programmes on the prevalence of N. meningitidis and the emergence of antimicrobial resistance. We found evidence that mass treatment programmes were associated with the emergence of antimicrobial resistance.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Improper lifting measures of long-span spatial steel structures during construction process may delay the construction period and even cause safety accidents. Few studies on long-span spatial steel structures considered time-varying mechanical characteristic during construction process. In order to achieve safe and efficient installation in a long-span spatial steel structure, this research presents a time-varying mechanical analysis of the synchronous and asynchronous integral lifting and a single and interlaced point’s asynchronous integral lifting analysis method of a long-span spatial steel structure. The results showed that in the case of asynchronous lifting of single point, the displacement influence on other members is related to the distance. The closer the distance from the lifting point, the greater the influence. In asynchronous integral lifting, the lifting point with large lifting force is first installed to the specified position, and the lifting point with small lifting force is installed to the specified position.

Gelatin industry residues are increasingly used as fertilizer and soil conditioner. However, correct residue dosage is critical for grass development and minimizing environmental impacts. This randomized block design study determined adequate dosage of Mixed Gelatin Sludge (MGS) for Marandu grass production in wet/dry seasons in Brazil. Five MGS levels (0%–200% of required nitrogen) were compared to mineral fertilizer. Agronomic/productivity characteristics, bromatological composition, macro/micro-nutrient composition of leaves, and soil chemical attributes were evaluated. Agronomic/productivity characteristics were influenced by MGS dose in both dry/rainy seasons, except for leaf blade pseudostem ratio and percentage of leaves/pseudostem. Bromatological composition was influenced by MGS doses in dry/rainy seasons except for dry/mineral material quantities. Marandu leaf tissue chemical composition was significantly influenced by MGS dose, except for potassium, boron, and iron. Chemical composition of four soil layers between 0–50 cm influenced GMS dose, except for pH, organic matter, magnesium, copper, manganese, and zinc. GMS dose for Marandu production should be 200% of nitrogen (N) requirement. GMS application increased productivity/quality of Marandu grass. Macronutrients (N, phosphorus) and micronutrients (Ca, Mg, S, Cu, and Zn) increased in Marandu grass and in the soil (Ca, S, and Na). Increased sodium (Na) level was not limiting.

BackgroundThe use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria. ObjectivesThis aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a Galleria mellonella model of Streptococcus pneumoniae infection. Methods A chronic model of S. pneumoniae infection in G. mellonella larvae was used for the experiment. Inoculation of larvae with S. pneumoniae was followed by injections of EMA (0.0875 μg/ml) and WHO (0.012 μg/ml) ADI doses of erythromycin proceeded by isolation of S. pneumoniae colonies on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications.   Results Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in S. pneumoniae. Emergent resistance to erythromycin was associated with a mutation in rplA. Conclusion In our in vivo model, even single dose of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in S. pneumoniae. These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs.

The continuous flowing spacetime forms a spacetime group G, one of its fundamental groups is the Poincare group PO(1,3), and the matter and interaction fields are representations of its intrinsic spacetime group. As a kind of quantized space-time unit, space-time group elements generate both space-time manifolds and matter. Matter and fields are aggregates of the quantum space-time within them and determine their type: the Lorentz group SO(1,3) represents a rotating spacetime corresponding to visible matter and the translation group P^1,3 represents a translational spacetime corresponding to dark matter and dark energy. The aggregation mode of space-time degrees of freedom in matter reveals that charge conjugation symmetry is the inverse symmetry of internal time of charged particles, and the external parity breaking of neutrinos is also due to their internal spatial aggregation mode.

Centrifugal pumps are widely employed in the oil refinery industry due to their efficiency and effectiveness in fluid transfer applications. The reliability of pumps plays a pivotal role in ensuring uninterrupted plant productivity and safe operations. Analysis of failure history data shows that bearings have been identified as critical components in oil refinery pump groups. However, traditional reliability estimation theories may not apply when data is limited or subject to right censoring. This paper addresses the complexity of estimating the Weibull distribution parameters using the maximum-likelihood method under the abovementioned conditions. The likelihood equation lacks an explicit analytical solution, necessitating the use of numerical methods for resolution. The proposed approach presented in this article leverages the Expectation-Maximization (EM) algorithm for estimating the Weibull distribution parameters. This method provides more accurate estimates of failure rates and probabilities by accounting for limited and censored data. The findings are demonstrated through a case study, showcasing the practical application of the proposed approach.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Epoxy asphalt (EA) concrete is widely used in constructing long-span steel bridge pavements (SBDPs). This study aims to derive a fatigue damage evolution law, conducting an experimental investigation of SBDP. First, a general theoretical form of the fatigue damage evolution law of materials is established based on the thermal motion of atoms. Then, fatigue experiments demonstrate that this evolution law well represents the known damage–life relationships of SBDP. Taking into account the experimental relationships between damage and fatigue life under symmetrical cyclic loadings with different overload amplitudes and temperature variations, a detailed damage evolution law is deduced. Finally, the role of damage accumulation is discussed on the basis of the proposed damage evolution law for the extreme situation of heavy overload and severe environments. The results show that both heavy loading and falling temperatures increase the fatigue damage of SBDP considerably; therefore, SBDP should avoid heavy loading combined with winter temperatures. EA shows a fatigue life two to three times longer than that of modified matrix asphalt (SMA) or guss asphalt (GA). For the same thickness, EA pavement is demonstrated to be more suitable for an anti-fatigue design of large-span SBDP under high traffic flows and low temperatures.

The brain being arguably the most complex organ in the human body, its detailed functioning is yet to be fully deciphered, let alone accurately modeled. Nonetheless, the medical community has gathered quite a remarkable amount of studies about the consequences of illnesses and injuries on its development and functioning. This bibliographic review aims to cover mostly the findings related to the changes in the physical distribution of neurons and their connections - the connectome -, both structural and functional, as well as their modelling. It does not intend to offer an extensive medical description of all injuries and diseases affecting the brain, rather presenting the most common ones succinctly so the need for accurate brain modelling can be fully understood and pondered, offering propositions to this aim.

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.

Electromobility has gained significant attention in the auto- motive industry, with car manufacturers striving to improve the charging experience for their users. In this study, we compare multiple realistic charging strategies in order to quantify the benefits arising from better planning of charging sessions. We base our evaluation on electricity price data from three regions: Sweden (SE3 region), Germany (DE region), and Denmark (DK2 region). This data is obtained from the ENTSO-E Transparency Platform, covering the two full years 2021 and 2022. We enhance this dataset with commercial price forecasts from the company StormGeo and benchmark it against a naive forecasting method. The primary aim of our work is to compare how the strategies of varying levels of complexity perform across the three different countries in terms of minimizing energy costs for electric car users.

In this work, several random Boolean networks (RBN) are generated and analyzed from two characteristics: their time evolution diagram and their transition diagram. To do this, its randomness is estimated using three metrics, of which algorithmic complexity is the only one capable of revealing both transitions towards the chaotic regime and the algorithmic contribution of certain states to the transition diagram and their relationship with the order they occupy in the temporal evolution of the respective RBN.

This paper discusses how mathematical models are used to predict environmental conditions. While these models are successful for larger scale phenomena, it becomes more complex for local weather or wave processes. Several approaches have been proposed to address this problem, including neural networks and statistical and mathematical models. The novelty in this approach is the use of statistical manifolds, which provide a more accurate way to estimate distances and cost functions. This work focuses on advancements in differential and information geometry for creating different types of models that can be used for environmental simulation and forecasting. These fields are vital for many institutes and centres worldwide, as they help solve challenges in areas such as meteorology, renewable energy, and aviation safety. Some potential IG applications to advance energy were given. Closing remarks with new open problems combined with the next research phase are provided.

We prove through path integral Monte Carlo computer experiments that the affine quantization of the $\varphi_4^4$ scaled Euclidean covariant relativistic scalar field theory is a valid quantum field theory with a well defined continuum limit of the one- and two-point-function. Affine quantization leads to a completely satisfactory quantization of field theories using situations that involve scaled behavior leading to an unexpected, $\hbar^2/\varphi^2$ which arises only in the quantum aspects.

The Semantic-Enhanced Tree-LSTM (SeT-LSTM) network, a novel advancement in the realm of linguistic modeling, marks a significant step forward from traditional Tree-based Long Short Term Memory (LSTM) networks. By intricately weaving in the nuances of typed grammatical dependencies, SeT-LSTMs offer a more nuanced understanding of language semantics. Traditional models often overlook the semantic shift caused by variations in word or phrase roles, a gap this paper aims to fill by focusing on the types of grammatical connections, or typed dependencies, within sentences. Our proposed architecture, dubbed the Semantic Relationship-Guided LSTM (SRG-LSTM), leverages a control mechanism to model the interplay between sequence elements. Additionally, we present a novel Tree-LSTM variant, the Semantic Dependency Tree-LSTM (SDT-LSTM), which integrates dependency parse structures with dependency types for more robust sentence embedding. The SDT-LSTM demonstrates superior performance in Semantic Relatedness Scoring and Sentiment Analysis compared to its predecessors. Qualitatively, it shows resilience to changes in sentence voice and heightened sensitivity to nominal alterations, aligning well with human intuition. This research underlines the pivotal role of grammatical relationships in sentence understanding and paves the way for further exploration in this domain.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

In small animal models of severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) infection, ferrets (Mustela putorius furo) have been used to investigate the pathogenesis. Podoplanin (PDPN) is an essential marker in lung type I alveolar epithelial cells, kidney podocytes, and lymphatic endothelial cells. Monoclonal antibodies (mAbs) against ferret PDPN (ferPDPN) are useful for the pathological analyses of those tissues. We previously established an anti-ferPDPN mAb, PMab-292 using the Cell-Based Immunization and Screening (CBIS) method. In this study, we determined the critical epitope of PMab-292 using flow cytometry. The N-terminal ferPDPN deletion mutants analysis revealed that the Val34 is located at the N-terminus of the PMab-292 epitope. Furthermore, the PA tag-substituted analysis (PA scanning) showed that Asp39 is located at the C-terminus of PMab-292 epitope. The epitope sequence (₃₄-VRPEDD-₃₉) also exists between Val26 and Asp31 of ferPDPN, indicating that PMab-292recognizes the tandem repeat of the VRPEDD sequence of ferPDPN.

A dataset collected from Central-South Finland is used to investigate the mortality of boreal trees. The mortality rate is found to be the order of three times that predicted by earlier Nordic mortality models, being in the upper range of international literature observations. Small subpopulations of any tree species tend to die out. Mortality of downy birch increases with stand basal area, as well as with stand age. Mortality of Norway spruce and silver birch increases after 100 years, while that of Scots pine is invariant to age. As the relative loss rate of basal area is insensitive to stand basal area, the mortality of trees does not strongly regulate thinning practices.

In recent years, humanity has faced a growing challenge posed by the rise of antibiotic-resistant bacteria, resulting in an alarming surge in fatalities and the emergence of increasingly hard-to-manage diseases. Among these resilient pathogens is Acinetobacter baumannii, due to its escalating prevalence in hospitals, elevated mortality rates, and resistance to treatment. Despite its clinical significance, our understanding of this pathogen in non-hospital settings and its virulence factors remains limited. Therefore, this review aims to shed light on the latest research regarding its ecological niche, microbiological traits, and antibiotic resistance profiles. Recent investigations have expanded its detection to various environmental niches, including rivers, treatment plants, and soils. Moreover, this bacterium has been discovered in diverse food sources such as meat and vegetables, as well as in farm animals and household pets like dogs and cats. This broader presence of Acinetobacter baumannii outside of hospital environments underscores a significant risk of environmental contamination, necessitating heightened awareness and preventive measures to address potential public health implications.

Green spaces localized in cities create favourable environmental conditions for Ixodes ricinus, the most widespread and important vector of tick-borne pathogens in Central Europe. In this study, we described the prevalence of Borrelia burgdorferi s.l. and Babesia species found in mono- and double infections among I. ricinus ticks occurring in urban areas of the city of Poznań, west-central Poland. Two tick groups were examined: (i) a group of 1,029 host-seeking ticks (460 nymphs, 289 females, and 280 males and (ii) a group of 1,268 engorged female ticks removed from 1,115 tick-infested animals, dogs and cats. The overall prevalence of B. burgdorferi s.l. found in host-seeking ticks was almost two-fold higher in comparison to ticks derived from pets (8.7 vs. 4.7%, respectively, χ2 test, P = 0.001). Borrelia afzelii and B. garinii were the most prevalent species both in ticks from vegetation (3.7% and 3.7%, respectively) and from pets (3.7% and 0.6%, respectively). Babesia infections were slightly more common in feeding ticks compared to those from vegetation (6.0 vs. 4.7%, respectively), however, the difference was not significant. Three Babesia species including Ba. microti, Ba. venatorum and Ba. canis were identified. Babesia canis and Ba. microti were the most prevalent in host-seeking (2.6% and 1.4%, respectively) and feeding ticks (2.8% and 2.2%, respectively), whereas Ba. venatorum was the rarest piroplasm. All Ba microti obtained sequences (n=42) were identical to Ba. microti genotype "Jena/Germany" that is considered as pathogenic to humans. Furthermore, the sequences of Ba. venatorum (n=17) were identical with those isolated from patients in Italy, Austria and Poland. Altogether, out of 121 Babesia-positive ticks, 19.8% were simultaneously infected with B. burgdorferi s.l. spirochetes. We found similar prevalences of co-infections in host-seeking (1.1%) as well as in feeding ticks (1.0%). In the first group, Ba. canis prevailed in coinfections (73%), mostly with B. afzelii and B. garinii, in the second group, Babesia microti dominated with B. afzelii (92.7%). This is the first finding documenting the co-occurrence of both pathogens in ticks from companion animals. The detection of Ba. microti and Ba. venatorum sequences identical to strains pathogenic to humans as well as predominance of LB spirochetes, B. afzelii and B. garinii in I. ricinus from vegetation and animals indicates that there is a potential risk of acquiring human babesiosis and/or Lyme borreliosis in urban areas of the city of Poznań. Although, the overall risk of encountering a Ba. microti and B. burgdorferi s.l. co-infected tick was low (1.0%), the potential for more severe clinical symptoms and complications deserves notice. A relatively high infection rates of Ba. canis in dog-derived ticks (3.2%) and in host-seeking ticks (2.6%), suggests that I. ricinus could potentially be involved in the circulation of this piroplasm in areas, where the competent vector, Dermacentor reticulatus is absent or rare.

This article seeks to strengthen efforts in technological developments based on the classification of PET plastic that positively impacts sustainable development and contributes to suitable solutions in collection centers in Mexico. Three experiment designs and machine learning tools for data processing were developed. For the experimentation, three factors were considered: the bottle's size, the amount of liquids inside the bottle, and the label on the bottle. The first experiment was to identify the distance of the sensor from post-consumer PET bottles. The second experiment was to determine the detection ability of the sensor with different levels of liquids inside the bottles, and the third was to determine the detection ability on the bottle labels. A digital lux meter on a microcontroller was developed to monitor illuminance on post-consumer PET plastic when it contains liquid as it passes through a conveyor belt for processing at an average rate of three bottles per second. With the implemented methodology, liquids were satisfactorily detected inside the transparent PET bottles when they had beverages between 25% and 100% of their capacity. Finally, this paper highlights that it is possible to implement an affordable design to identify bottles with liquids for collection centers.

The ordinary 3D wave equation for nondissipative, homogeneous, isotropic media admits solutions where the point sources are permitted to move, but it does not admit solutions where the receiver is allowed to move. To overcome this limitation, the new wave equation is derived, permitting both the receiver and the source to move. This new wave equation is a generalization of the standard wave equation, and it reduces to the standard wave equation when the receiver is at rest. To derive this new wave equation, we first mathematically define a diverging spherical wave caused by the stationary point source. From this purely mathematical definition, the wave equation for the stationary source and the moving receiver is derived together with the corresponding free-space Green's function. Utilizing the derived Green's function, it was shown that this new wave equation also permits the solutions where both the receiver and the source are permitted to move. In conclusion, this paper demonstrates that, instead of an ordinary wave equation, the wave equation for the moving source and the moving receiver governs the waves emitted by the moving point sources and received by the moving receivers.

The future index prices are viewed as a critical issue for any trader and investor. For this craving, various models have shown up in the literature. The Geometric Brownian motion (GBM) is one of the popular models. This work examines four types of GBM as per the presence of memory or kind of volatility. These models include classical GBM with memoryless and constant volatility assumptions, SVGBM with memoryless and stochastic volatility assumption, GFBM with memory and constant volatility assumption, and SVGFBM with memory and stochastic volatility assumption. These models are utilized in an empirical study to forecast the future index price of Energy Sector in the Saudi Stock Exchange Market. The assessment was led by utilizing two error standards, mean square error (MSE) and mean absolute percentage error (MAPE). The outcomes showed that the SVGFBM occupies the highest level of accuracy according to smallest values of MSE and MAPE. While the accuracy of GBM come in the tail of the list models under study. These results have affirmed the positive affection of combining memory and stochastic volatility assumption into the GBM model, which agreed findings of numerous earlier works. Furthermore, the findings showed the GFBM models are more accurate than GBM models regardless of the type of volatility. While, under the same type of memory, the models with stochastic volatility assumption are more accurate than the corresponding models of constant volatility assumption. In general, all models considered in this work uncovered high accuracy through the value of MAPE ≤ 10%. This indicates of the ability of applying these models in a real financial environment. Through this empirical study, we can say that the Energy Sector in Saudi Arabia is predictable and stable and afterward we urge financial investors and stockholder to trade and invest in this sector.

The fate of critically sick patients with infections in intensive care units (ICUs) is significantly influenced by antimicrobial resistance, which has become a serious concern in developing nations. This observational study was conducted at the IBN Sina Specialised Hospital in Dhaka, Bangladesh, over a 12-month period from January 2021 to December 2021, in order to track the pattern of antibiotic resistance among the patients admitted to the intensive care unit (ICU). Aspiration pneumonia (29%) and diabetes mellitus (24%), among 200 patients, were the most common main diagnoses. 65 samples (or 26%) of the 250 samples had 85 bacteria identified from them. Urine (14.12%) and tracheal aspirate (64.71%) were the most frequently found sites of infection. In the sample from the tracheal aspirate, Pseudomonas spp. (30.59%), Escherichia coli (24.71%), Acinetobacter spp. (20%), and Klebsiella spp. (14.12) were the most frequently isolated microorganisms. The following antibiotics were shown to have the highest overall patterns of resistance: levofloxacin (68.24), amikacin (64.71), meropenem (49.41), ceftazidime (75.29), ciprofloxacin (78.82), and gentamicin (82.35). The most effective antibiotic against Klebsiella species was meropenem (64.61%), while Acinetobacter species were mostly susceptible to cotrimoxazole (64.67%) and piperacillin + tazobactam (60.50%). Most susceptible to netilmicin (70.48%) and meropenem (49.32%) were Escherichia coli, while Pseudomonas spp. were mostly responsive to colistin (55.14%) and netilmicin (52.25%). Antibiotic resistance is common among intensive care unit (ICU) patients, and most isolated microbes have resistance to traditional medicines.

A three-year survey was conducted to estimate the incidence of grapevine trunk diseases (GTDs) in Greece and identify fungi associated with the disease complex. In total, 310 vineyards in different geographical regions in northern, central, and southern Greece were surveyed, and 533 fungal strains were isolated from diseased vines. Morphological, physiological and molecular (5.8S rRNA gene-ITS sequencing) analyses revealed that isolates belonged to 35 distinct fungal genera, including well-known (e.g. Botryosphaeria sp, Diaporthe spp., Eutypa sp., Diplodia sp., Fomitiporia sp., Phaeoacremonium spp., Phaeomoniella sp.) and lesser-known (e.g. Neosetophoma sp., Seimatosporium sp., Didymosphaeria sp., Kalmusia sp.) grapevine wood inhabitants. GTDs-inducing population structure differed significantly among the discrete geographical zones. Phaeomoniella chlamydospora (26.62%, n=70), Diaporthe spp. (18.25%, n=48) and F. mediterranea (10.27%, n=27) were the most prevalent in Heraklion, whereas D. seriata, Alternaria spp., P. chlamydospora and Fusarium spp. were predominant in Nemea (central Greece). In Amyntaio and Kavala (northern Greece), D. seriata was the most frequently isolated species (&gt;50% frequency). Multi-genes (rDNA-ITS, LSU, tef1-α, tub2, act) sequencing of selected isolates, followed by pathogenicity tests revealed that Neosetophoma italica, Seimatosporium vitis, Didymosphaeria variabile and Kalmusia variispora caused wood infection with the former being the most virulent. To the best of our knowledge, this is the first report of N. italica associated with GTDs worldwide. This is also the first record of K. variispora, S. vitis and D. variabile associated with wood infection of grapevine in Greece. The potential associations of disease indices with vine age, cultivar, GTD-associated population structure and the prevailed meteorological conditions in different viticultural zones in Greece are presented and discussed.

This research explores the predictive capabilities of autonomous driving systems by integrating human factor considerations within the context of safety-critical events. Recognizing the significance of human behaviors in influencing driving dynamics, the study employs advanced modeling techniques to enhance the accuracy of predictions in scenarios that demand heightened safety measures. Traditional rule-based systems and monotonic logic often fall short in addressing the complexities of safety-critical events. To overcome these limitations, the research proposes the application of non-monotonic logic, allowing for flexible and adaptive reasoning that accommodates exceptions and context-specific information.The study emphasizes the importance of incorporating individual differences among drivers, such as risk-taking tendencies, reaction times, decision-making processes, and driving styles. By considering these human factors, the research aims to develop realistic and accurate autonomous driving models that capture the nuances of real-world driving scenarios, especially in safety-critical situations. The predictive model takes into account both internal and external factors, enabling the autonomous system to anticipate and respond effectively to unforeseen events.The primary goal is to provide autonomous vehicles with the capability to make plausible inferences, handle conflicting data, and adapt their behavior in real-time during safety-critical events. The proposed model integrates personalized cognitive agents for each driver, incorporating their unique preferences, characteristics, and needs. This personalized approach aims to optimize the safety and efficiency of autonomous driving, contributing to the ongoing evolution of intelligent transportation systems.In conclusion, this research contributes to advancing the field of autonomous driving by introducing a predictive model that leverages human factor considerations to enhance safety in safety-critical events. The incorporation of non-monotonic logic and individualized cognitive agents signifies a comprehensive approach to address the challenges associated with predicting autonomous driving behavior, paving the way for safer and more reliable autonomous vehicles in dynamic and unpredictable environments.

Background: The bacterium Capnocytophaga spp. is a part of the oral microbiome of dogs, which has zoonotic potential. This study aimed to assess factors that influence the prevalence of Capnocytophaga cynodegmi and Capnocytophaga canimorsus in Wrocaw’s dog population. Methods: Molecular detection (PCR) involved 105 swabs, examining parameters such as oral cavity condition, underlying health issues, recent antibiotics, age, medications, material collection, and dog chews. Results: The study highlighted significant associations between the presence of Capnocytophaga cynodegmi and oral cavity condition, material collection method, and use of dog’s chews. Conclusions: Correlations obtained in this study between the oral health of Wroclaw's dog population and the presence of Capnocytophaga cynodegmi suggest its significance in the oral microbiome of dogs. Limitations, including the small sample size, highlight the need for more research to comprehensively understand additional factors that affect the prevalence of Capnocytophaga spp. in dogs

Boswellia trees are the source of frankincense, which can be found throughout the Middle East and parts of Africa and Asia. Boswellia serrata extract has been shown to have anti-cancer, anti-inflammatory, and anti-microbial effects. Periodontitis is an oral chronic inflammatory disease that affects nearly half of the US population. We investigated the antimicrobial effects of B. serrata extract on two oral pathogens associated with periodontitis. Using the minimum inhibitory concentration and crystal violet staining methods, we demonstrated that Porphyromonas gingivalis growth and biofilm formation were impaired by treatment with B. serrata extracts. However, there were no significant effects on Fusobacterium nucleatum growth and biofilm formation. Using colony-forming units quantification and microscopy techniques, we also showed that concentrations of B. serrata that were not toxic for host cells decreased intracellular P. gingivalis infection in human gingival epithelial cells. Our results show antimicrobial activity of a natural product extracted from Boswellia trees (B. serrata) against periodontopathogens. Thus, B. serrata has the therapeutic potential for preventing and/or treating periodontal diseases. Future studies will identify molecular components of B. serrata extracts responsible for the beneficial effects.

Celtis sinensis is an adaptable species that is widely grown in southern China. In June 2022, a leaf blotch disease of C. sinensis was observed in Nanjing, Jiangsu, China. Based on morphological characterization, three isolates were identified as Alternaria species. Phylogenetic analysis of combined ITS, GAPDH, TEF1-α, RPB2 and Alt a 1 sequences identified the three isolates we obtained as Alternaria alternata and Alternaria koreana. Koch’s postulates were fulfilled in the greenhouse, and the pathogenicity of A. alternata and A. koreana was determined by leaf inoculation tests on C. sinensis seedlings. The symptoms of indoor inoculation were consistent with those in the field. A. alternata and A. koreana can grow at 15-35 °C, with an optimal growth temperature of 25 °C. The results of fungicide sensitivity experiments indicated that A. alternata and A. koreana were the most sensitive to prochloraz, which may be a useful strategy for the future prevention and control management of A. alternata and A. koreana. This study provides the first step for further research on A. alternata and A. koreana as pathogens of C. sinensis and provides a theoretical basis for future control strategies.

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.

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.

This study focuses on examining various approaches for Tensor Decompositions (TDs) and their potential applications in satellite imaging (SI) and deep learning (DL). The research highlights how these decompositions can contribute to the advancement of SI and DL, providing valuable insights for future utilization of TDs in research. It explores how these techniques contribute to the advancement of SI and DL methods, providing insights into their potential applications and suggesting future research directions. The study aims to enhance the use of TDs techniques to further advance research efforts in these fields. More importantly, the current investigation offers a thorough analysis of the potential advantages and reasons for employing TDs techniques in different domains, including satellite imaging and deep learning. The aim is to enhance research outcomes by utilizing TDs. The review also identifies unresolved issues and proposes future directions for further investigation in this field. Fundamentally, these proposed open problems will open new grounds to the research community to articulate, innovate, and provide more real-life applications to improve the current state of the art by delving into a wider vision for a higher-level performance of both satellite imaging (SI) and deep learning (DL). Looking at the bigger scenario, this also suggests that TDs could be potentially employed to revolutionize existing machine learning technologies as well as the current space AI industry.

Pathogenic Neisseria gonorrhoeae causes the sexually-transmitted infection gonorrhea. N. gonorrhoeae has evolved high levels of antimicrobial resistance (AR) leading to therapeutic failures even in dual-therapy treatment with azithromycin and ceftriaxone. AR mechanisms can be acquired by genetic transfer from closely related species, such as naturally-competent commensal Neisseria species. At present, little is known about the antimicrobial resistance profiles of commensal Neisseria. Here, we characterized the phenotypic resistance profile of four commensal Neisseria species (N. lactamica, N. cinerea, N. mucosa, and N. elongata) against 10 commonly used antibiotics, and compared their profiles to 4 N. gonorrhoeae strains, using disk diffusion and minimal inhibitory concentration assays. Overall, we observed that 3 of the 4 commensals were more resistant to several antibiotics than pathogenic N. gonorrhoeae strains. Next, we compared the penicillin-binding-protein 2 (PBP2) sequences between commensal and N. gonorrhoeae strains. We found mutations in PBP2 known to confer resistance in N. gonorrhoeae also present in commensal Neisseria sequences. Our results suggest that commensal Neisseria have unexplored antibiotic resistance gene pools that may be exchanged with pathogenic N. gonorrhoeae, possibly impairing drug development and clinical treatment.

Neisseria meningitidis outer membrane vesicles or proteoliposomes (PLs) has been used as vaccines and adjuvant. Despite the presence of potentially toxic amounts of lipopolysaccharide (LPS), they have been shown to be safe, well tolerated, and immunogenic. This suggests that LPS-PL may have reduced LPS toxicity. We show here that the ability of PL to induce pro-inflammatory cytokine production in human U937 histiocytic cell line is significantly lesser than that of an equivalent concentration of purified LPS, thus confirming that certain components or physical properties of PL reduce the pro-inflammatory activity of their endogenous LPS. To investigate the mechanisms responsible for this protective effect, PLs were fractionated and assayed the ability of the resulting fractions to induce inflammatory cytokine expression. Several individual PLs fractions were more potent inducers of pro-inflammatory cytokine production than the unfractionated PLs. The majority of the pro-inflammatory activities appeared to be mediated by the presence of LPS in the fractions, as shown by the ability of an anti-CD14 antibody to block it. However, in two PL fractions, the production of IL-8 and to a lesser extent IL-6 was not inhibited by anti-CD14 treatment, indicating that pro-inflammatory components other than LPS could also be present in PL. Eight proteins present in the fractions were identified by n-terminal sequencing. Our results suggest that two of them PorB and particularly the RmpM protein may also contribute to the pro-inflammatory activity of N. meningitidis PL. Our results could support the development of PLs as vaccine adjuvant.

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.

: Poultry products in Zambia form an integral part of the human diet in many households, as they are cheap and easy to produce. The burden of poultry diseases has, however, remained a major challenge. Growing consumer demand for poultry products in Zambia has resulted in non-prudent antimicrobial use on farms, intending to prevent and treat poultry diseases for growth optimization and maximising profits. This cross-sectional study aimed to identify the different types of bacteria causing diseases in chickens in Lusaka and to detect the extended-spectrum-lactamase (ESBL)-encoding genes. We collected 215 samples from 91 diseased chickens at three post-mortem facilities and screened them for gram-negative bacteria. Of these samples, 103 tested positive for various clinically relevant Enterobacteriaceae, including Enterobacter (43/103, 41.7%), Escherichia coli (20/103, 19.4%), Salmonella (10/103, 9.7%), and Shigella (8/103, 7.8%). Other isolated bacteria included Yersinia, Morganella, Proteus, and Klebsiella, which accounted for 21.4%. E. coli, Enterobacter, Salmonella, and Shigella were subjected to antimicrobial susceptibility testing. The results revealed that E. coli, Enterobacter, and shigella were highly resistant to tetracycline, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole, while Salmonella showed complete susceptibility to all antibiotics. The observed resistance patterns correlated with antimicrobial usage estimated from sales data from a large-scale wholesale and retail company. Six (6/14, 42.9%) E. coli isolates tested positive for bla_CTX-M, whilst eight (8/14, 57.1%) Enterobacter samples tested positive for bla_TEM. Interestingly, four (4/6, 66.7%) of the E. coli isolates carrying bla_CTX-M-positive strains were also positive for bla_TEM. Sanger sequencing of the PCR products revealed that five (5/6,83.3%) of the abovementioned isolates possessed the bla_CTX-M-15 allele. The results suggest the presence of potentially pathogenic ESBL-producing Enterobacteriaceae in poultry, threatening public health. Keywords:. Enterobacteriaceae, bla_CTX-M, bla_TEM

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. Previously, we developed a sublingual vaccine formulated with the SARS-CoV-2 receptor binding domain antigen and Poly(I:C) adjuvant in nonhuman primates, cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvant and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccineproduced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines—IFN-alpha, IFN-gamma, and IL-17—in the blood, nor upregulated the gene expression of proinflammatory cytokines—IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B—in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with Poly(I:C) adjuvant is safe and creates a balanced state of enhancing and suppressing the immune-related response.

The work contains a detailed analysis of the electromagnetic field originating from a point source placed above the layered structure.The surface impedance of the multilayer dielectric structure was determined. Based on the boundary conditions, a method for determining the surface impedance of a layered structure with a perfectly conductive screen and or a magnetic screen is presented. The resonance conditions and the conditions for the excitation of surface waves are derived. The integral expression defining the generalized impedance was analyzed with a view to adapting it to numerical implementation. This allowed the development of a computer program based on which calculations were made of the effect of excitation of waves on multilayer dielectric substrates.

Conventional text style transfer (TST) methodologies primarily utilize style classifiers to segregate the content and stylistic elements of text for effective style transformation. Despite the pivotal role of these classifiers, their influence on TST techniques remains largely unexplored. This study embarks on a detailed exploration of the limitations inherent in style classifiers within current TST frameworks. We reveal that these classifiers often inadequately comprehend sentence syntax, leading to diminished performance in TST models. In response, we introduce the Syntax-Enhanced Style Transfer (SEST) model, a groundbreaking approach incorporating a syntax-sensitive style classifier. This classifier ensures that the extracted style representations robustly encapsulate syntax nuances, enhancing TST effectiveness. Rigorous evaluations across diverse TST benchmarks demonstrate that SEST significantly surpasses contemporary models in performance. Additionally, our case studies highlight SEST's proficiency in producing syntactically coherent sentences that aptly retain original content.

Spodopotera frugiperda is a worldwide invasive pest that has caused major economic damage. According to classical biological control theory, natural enemies that can control invasive pests come from the area of origin as the pests that have gone through coadaptation processes. However, the new association’s approach suggests that local natural enemies are equally capable to control invasive pests. Due to the lack of data on the association of S. frugiperda and local natural enemies, research was conducted through a rapid survey to study the population density of S. frugiperda in Yogyakarta, Indonesia and to study the diversity of parasitoid associated with S. frugiperda. The results showed the difference in S. frugiperda population and parasitism rate, with 15 parasitoid species associated with S. frugiperda. Four egg parasitoids, eight larval parasitoids, and three pupal parasitoids were found to be associated with S. frugiperda for three years after it was first discovered in Indonesia. A new association was found between S. frugiperda and three parasitoid species, consisting of two egg parasitoids (Platygasteridaesp.01 and Platygasteridaesp.02) and a larval parasitoid (Eupelmidaesp.01). A relatively new association was found between S. frugiperda and two larval parasitoids (Coccygidium sp. and Stenobracon sp.), and an existing association was found between seven species including an egg parasitoid Telenomus remus, three larval parasitoids (Cotesia sp., Microplitis sp., Campoletis sp.), and three pupal parasitoids (Brachymeria lasus, B. femorata, and Charops sp.). Telenomus remus is the most dominant parasitoid, with a higher abundance and parasitism rate. This study also reported the first findings of the association of S. frugiperda with the larval parasitoid Megaselia scalaris in Indonesia. The result suggests another method for biological control using the new association approach since local natural enemies can foster quick adaptation to invasive pests.

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.

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.

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.

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. Colitis severity was evaluated using histology and colonoscopy. Mice were mono-inoculated with C. albicans, C. tropicalis or co-challenged with both species. Mice were administered 3% DSS to induce acute colitis. Biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) assay. Abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. Co-challenged mice showed decreased colitis severity compared to mono-inoculated mice. The XTT assay demonstrated a marked decrease of C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface leading to a reduction in biofilm formation.

Maintaining the high overall health of farmed animals is a central tenant of their well-being and care. Intense animal crowding in aquaculture promotes animal especially in the absence of straightforward methods for monitoring their health. Here, we used bacterial 16S ribosomal RNA gene sequencing to measure population dynamics occurring during P. salmonis outbreaks. Our findings revealed a complex bacterial community consisting of a previously undescribed core pathobiome. Notably, we detected Aliivibrio wodanis and Tenacibaculum dicentrarchi on the skin ulcers of salmon infected with P. salmonis, while Vibrio spp. were enriched on infected gills. The prevalence of these co-occurring networks indicates the influence that coinfection plays in P. salmonis pathogenicity.

This study aimed to assess the microbiological quality of set of fruits and vegetables sold on stalls in the streets and open markets of Dakar, the capital city of Senegal. Samples purchased in seven sites were analyzed to isolate E. coli, Salmonella spp. and Vibrio spp. Some primary samples with a positive microbiological culture were subjected to DNA extraction and subsequent metagenomic analysis. A total of 240 fresh fruit and vegetable samples were collected including lettuce (n=40), tomatoes (n=40), mango slices (n=40), onion slices (n=40), mint leaves (n=40), strawberries and grapes (respectively n=20). Of these samples, 50.83% (122/240) and 60.41% (145/240) was contaminated with Escherichia coli and Vibrio spp. respectively, while Salmonella was not isolated in any product. Levels of contamination with both E. coli (1.3 103 to 6 106 CFU/g) and Vibrio spp. (4.55 102 to 8.73 106 CFU/g) were significantly above the thresholds acceptable for human consumption. The most contaminated samples were lettuce with a prevalence of 98% (39/40) for E. coli and for Vibrio spp. followed by mint leaves with 100% (40/40) and 93% (37/40) of the samples containing for E. coli and Vibrio spp. respectively. Out of 46 samples sequenced, metagenomic analysis revealed high contamination rates for E. coli, Vibrio spp. and Salmonella spp. with 100%, 67.39% and 93.47% of prevalence respectively. On the other hand, the alpha diversity analysis shows a high bacterial diversity in lettuce and mint leaf samples while beta diversity analysis highlighted the presence of two major clusters. Our results stress the need of a surveillance system that extends this investigation to a national scale while increasing the number of sampling sites and products analyzed.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Despite recent improvements in the methods used to eradicate and minimize mosquito populations, they still pose severe threats to human health. This study aimed to investigate the Larvicidal potentials of silver nanoparticles of Ocimum gratissimum on wild Anopheles larvae from Lagos. The plant used in this study was collected from the southeastern part of Nigeria, Ibite-Olo in Ezeagu Local Government Area of Enugu State. Wild Anopheles mosquito larvae were collected from a field at Kosofe Local Government Area of Lagos State, Nigeria where resistant Anopheline populations have been reported in and around Lagos State were brought to the laboratory and kept under standard insectary conditions (25–29 °C;78–82% relative humidity). Aqueous extract of Ocimum gratissimum was made and subsequently into the silver nanoparticles. A bioassay test was performed according to WHO guidelines, with six different concentrations to assess the larvicidal activity and values obtained were subjected to log prohibit regression analysis to obtain LC₅₀ and values with 95% confidence limit. The results of the larvicidal activities of the silver nanoparticles of Ocimum gratissimum showed that the mortality rate was dose-dependent with the percentage mortality increasing at a direct proportional rate as with dose and time of exposure. Ocimum gratissimum gave LC₅₀ at 0.5 ppm and LC₉₅ at 2.5 ppm respectively. The biosynthesized silver nanoparticles augmented the larvicidal activity of the silver nanoparticles of Ocimum gratissimum on wild Anopheles larvae from Lagos. Therefore, this study showed that the silver nanoparticles of Ocimum gratissimum have the potency to be used against an insecticide-resistant mosquito vector and are a suitable candidate for the development of novel natural insecticides.

Sexually transmitted infections (STIs) such as Gonorrhea is associated with serious morbidity and mortality rates in the world considering the multiple virulence factors possessed. The disease is manifested as salpingitis, pelvic inflammatory disease (PID), and bacteremia and is controlled by macrophages, dendritic cells, neutrophils, T cells, epithelial cells and cytokines. Dihydroliponamide acetyltransferase, a component of the mitochondrial pyruvate complex can be used as immunogenic target. Recent changes in the strain allowed the bacteria to acquire resistance against antibiotics.Vaccination remains an alternative to prevention against the disease. This study predicts an effective epitope-based vaccine against dihydrolipoamide acetyltransferase of Neisseria Gonorrhea using immunoinformatics approaches. Sequences retrieved from NCBI were passed on several prediction tests to analyze for possible B-cell, T-cell MHC class I epitopes and class II. Two epitopes showed high binding affinity for B-cells, while thirteen epitopes showed high binding affinity for MHCI and forty-five for MHCII. A population coverage of 100% for combined MHC I and II dictates the huge number of individuals who will benefit from formulating the vaccine. We recommend invivo and invitro studies to prove our prediction results.

Ixodes scapularis is a blood-feeding obligate ectoparasite responsible for transmitting the Lyme disease (LD) agent, Borrelia burgdorferi. During the feeding process, I. scapularis injects B. burgdorferi into the host along with its saliva, facilitating the transmission and colonization of the LD agent. Tick calreticulin (CRT) is one of the earliest tick saliva proteins identified and is currently utilized as a biomarker for tick bites. Our recent findings revealed elevated levels of CRT in the saliva proteome of B. burgdorferi-infected I. scapularis nymphs compared to uninfected ticks. Differential precipitation of proteins (DiffPOP) and LC-MS/MS analyses were used to identify the interactions between Ixs (I. scapularis) CRT and human plasma proteins and further exploring its potential role in shielding B. burgdorferi from complement killing. We observed that although yeast expressed recombinant (r) IxsCRT binds to the C1 complex (C1q, C1r, and C1s), the activator of complement via the classical cascade, it did not inhibit deposition of the membrane attack complex (MAC) via the classical pathway. Intriguingly, rIxsCRT binds intermediate complement proteins (C3, C5, and C9) and reduces MAC deposition through the lectin pathway. Despite inhibition of MAC deposition in the lectin pathway, rIxsCRT did not protect a serum sensitive B. burgdorferi strain (B314/pBBE22Luc) from complement-induced killing. As B. burgdorferi establishes a local dermal infection before disseminating to secondary organs, it is noteworthy that rIxsCRT promotes the replication of B. burgdorferi in culture. We hypothesize that rIxsCRT may contribute to the transmission and/or host colonization of B. burgdorferi by acting as a decoy activator of complement and by fostering B. burgdorferi replication at the transmission site.

Chronic kidney disease (CKD) is characterized by a continuous decline in kidney function, often persisting for years or even a lifetime. This study presents a new exploration into the extraction and application of insect chitosan (Tenebrio molitor) targeting hemodialysis (HD). Initially, the potential of insect-derived chitosan as a sustainable and effective alternative to traditional sources (i.e. crustaceans) is demonstrated. Efficient extraction methods were developed (totaling between 6 h and 12 h), producing chitosan. Firstly, chitin was efficiently isolated from T. molitor through deproteinization and demineralization, with yields of approximately 5% (w/w). Subsequently, chitosan was obtained from the extracted chitin resulting in yields of between 65.0 ± 0.8% (w/w) and 79.3 ± 0.8% (w/w). Characterization using Fourier Transform Infrared Spectroscopy (FTIR) confirmed structural similarities with commercial chitosan and degrees of deacetylation in the 73 - 75% range. The bioactive properties of chitosan obtained from T. molitor, including antimicrobial and antioxidant activities, were evaluated. All the microorganisms tested were inhibited, exhibiting minimum lethal concentrations between 2 and 8 mg/mL, confirming the antimicrobial activity of the extracted chitosan. In addition, chitosan showed antioxidant activity in the range of 60 to 65 µmol Trolox equivalent/g, suggesting its viability for various medical applications.This study also developed a chitosan-based membrane (CH - M) culminating in a proof-of-concept phase for hemodialysis. The permeation characteristics of CH-M for urea and albumin were studied in vitro to assess their suitability as HD membranes. Urea was permeable to values of over 70% and albumin was retained.

Paratuberculosis, or Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis affecting both domestic and wild ruminants. The agent was also found in wild mammals such as wild boar (Sus scrofa), however, the role of wild mammals in the epidemiology of MAP is unclear. During the research period, 941 free-ranging wild boar (S. scrofa) legally hunted in two locations in the Centre-eastern region of Portugal were examined. Ninety-seven wild boar exhibited one or more gross lesions and were tested for the presence of Mycobacterium avium subsp. paratuberculosis using acid-fast staining, mycobacterial culture, poly-merase chain reaction (PCR), and histopathological examination. Forty-five animals (46.4%, 95% CI: 36.5-56.3%) were identified as infected, as indicated by positive results in culture and/or PCR. The findings revealed that the most significant risk factor was being a juvenile compared to year-lings and adults (OR = 10.2, 95% CI: 2.2-48.0). Based on our results, 37.9% (n = 11) of the infected animals were considered suitable for human consumption. Our findings offer novel insights into mycobacterial infections in wild boar populations in Portugal and suggest that wild boar could be a source of human infection if zoonotic potential is considered.

Metagenomic analysis of Aedes aegypti and Ae. albopictus mosquitoes from diverse geographical regions of India revealed presence of several insect viruses of human interest. Most abundant reads found in Ae. aegypti mosquitoes were Phasi-Charoen like virus (PCLV), Choristoneura fumiferana granulovirus (CfGV), Cell fusing agent virus (CFAV) and Wenzhou sobemo-like virus 4 (WSLV4), whereas WSLV4 and CfGV constituted the highest percentage in Ae. albopictus viromes. Other reads which were of low percentage included Hubei mosquito virus 2, Porcine astrovirus 4 and Wild Boar astrovirus. PCLV and CFAV, which were found to be abundant in Ae. aegypti viromes, were absent in Ae. albopictus viromes. Among the viromes analyzed, Ae. aegypti sampled from Pune showed highest percentage (79.82%) of viral reads while Ae. aegypti mosquitoes sampled from Dibrugarh showed lowest percentage (3.47%). Shamonda orthobunyavirus, African swine fever virus, Aroa virus and Ilheus virus, having potential to infect vertebrates including humans, were also detected in both mosquito species, albeit in low read numbers. Reads of gemykibivirus, avian retrovirus, bacteriophages, herpesviruses and viruses infecting protozoans, algae, etc. were also detected in the mosquitoes. A high percentage of reads in the Ae. albopictus mosquito samples remained unclassified and warrant further investigation. Data generated in the present work may not only lead to studies to explain the influence of these viruses on replication and transmission of viruses of clinical importance but also find application as biocontrol agents against pathogenic viruses.

The predatory mirids Macrolophus pygmaeus Ramber and Nesidiocoris tenuis Reuter (Heteroptera: Miridae) are used for the biological control of Tuta absoluta Meyrick (Lep.: Gelechiidae) and other pests in tomato greenhouses. The functional response of 1 (young) and 10 (old) days old adult females and males of M. pygmaeus and N. tenuis on eggs of T. absoluta, was determined on tomato at two temperatures (20° and 25°C) and LD 16:8 and found to be Type II. M. pygmaeus females exhibited higher predation efficiency, than males at both tested temperatures. Young M. pygmaeus females had a higher efficiency than old ones, whereas males had a low efficiency irrespective of age. The predation efficiency of N. tenuis was high (but lower than M. pygmaeus) in both young females and males, although old females had a higher efficiency than the respective males. Our results show that the two predatory species have different functional response characteristics to their prey depending mainly on sex and age which may affect their role as biological control agents.

Burkholderia are a group of Gram-negative bacteria that can cause a variety of diseases in at-risk populations. B. pseudomallei and B. mallei, the etiological agents of melioidosis and glanders, respectively, are the two clinically relevant members of the B. pseudomallei complex (Bpc). The development of vaccines against Bpc species has been accelerated in recent years, resulting in numerous promising subunits and glycoconjugate vaccines incorporating a variety of antigens. However, a second group of pathogenic Burkholderia species exists known as the Burkholderia cepacia complex (Bcc), a group of opportunistic bacteria which tend to affect individuals with weakened immunity or cystic fibrosis. To date there have been few attempts to develop vaccines to Bcc species. Therefore, the primary goal of this review is to provide a broad overview of the various subunit antigens that have been tested in Bpc species, their protective efficacy, study limitations, and known or suspected mechanisms of protection. Then, we assess the reviewed Bpc antigens for their amino acid sequence conservation to homologous proteins found in Bcc species. We propose that protective Bpc antigens with a high degree of Bpc-to-Bcc sequence conservation could serve as components of a pan-Burkholderia vaccine capable of protecting against both disease-causing groups.

This paper is a brief review of our own work on the Planck quantized version of general relativity theory. It demonstrates several other straightforward methods to simply rewrite the same equations that we have already presented.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

Studies have established the crucial role of sleep among the students which plays a significant role in their mood. This study aimed to examine the mood disorders and sleep quality among undergraduate students at the University of Georgia (UG) and comparison between students’ nationality.This cross-sectional study was a self-reported questionnaire comprised of demographics including age, gender, year of study, current location, lifestyle data (Exercise and smoking), the Depression, Anxiety, and Stress Scale (DAS21) and the Pittsburgh Sleep Quality Index (PSQI). We performed a descriptive analysis, and the Chi-square was statistically significant at p<0.05. The prevalence was at a 95% confidence interval (95% CI) as multivariate analysis examined the multicollinearity. The female students were most of the respondents, below the age of 20 years. The student's mean age was 20.20 (SD± 3.0). DAS report presented 72.7% of students with depressive symptoms, 77.8% with anxiety symptoms, and 62.2% had stress. Georgian students were more at risk of having depressive complaints (95% Cl[1.567-3.788]), anxiety (95% Cl[1.612-4.285]), and stress symptoms (95% Cl[1.743-3.831]). There was a strong relationship between the students who experienced poor sleeping patterns and depressive complaints (aOR 0.10). The students who were smokers (aOR 0.39) were more likely to report anxiety symptoms than the students that do not exercise (aOR 1.68). It was observed that students with depressive symptoms, anxiety, and complaints of stress had a significantly high risk of poor sleep quality. Further studies are recommended to curb psychological symptoms of mood changes in association with sleep disorders among students.

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.

Security in the Internet of Things (IoT) is a critical concern due to the growing number of connected devices and the limited resources to implement robust security mechanisms in most of them. Adopting standard assessment frameworks, such as CVSS (Common Vulnerability Score System), allows for systematic vulnerability assessment. At the same time, CVE (Common Vulnerabilities and Exposures) records provide unique identifiers for known security issues, making it easier to share information. However, comparing security solutions is still challenging due to the diverse nature of IoT devices and the ever-evolving threat landscape, requiring continual innovation and collaboration between stakeholders. Furthermore, there still needs to be a simple way to compare technologies and solutions, taking into account the security provided by them. In this sense, in this article, we propose a tool for calculating a security score based on the CVSS index of each existing vulnerability in a given technology. We explain how the tool performs the calculation, discuss some challenges, and propose improvements for future work.

Coastal resources in Lian, Batangas, have undergone significant degradation due to a combination of human activities and natural factors, including sea-level rise, changes in sea-surface temperature, fluctuations in rainfall, increased storm frequency, and sedimentation. This has led to adverse effects on key ecosystems such as corals, mangroves, and seagrasses. To assess the extent of climate change hazards on these coastal resources, a Vulnerability Assessment was conducted in the municipality of Lian, Batangas. The assessment employed a combination of the Coastal Integrity Vulnerability Assessment Toolkit (CIVAT) and Integrated Coastal Sensitivity, Exposure, and Adaptive Capacity to Climate Change (ICSEA-C) guidelines. Additionally, the analysis incorporated detailed mapping using Light Detection and Ranging (LiDAR) data for mangroves and LandSat 8 imagery for corals and seagrasses. The findings at the municipal scale revealed that a staggering 90% of mangroves in Lian, Batangas, were highly vulnerable. This vulnerability was attributed to a high score in intrinsic characteristics and a low adaptive capacity. Similarly, a majority of seagrasses in the area were classified as medium and highly vulnerable at the municipal level. Only 10–20% of seagrasses received low to medium vulnerability scores. Shockingly, almost 100% of the coral reefs in Lian, Batangas, were deemed highly vulnerable, indicating a critical threat to this crucial marine ecosystem.

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with a progressive loss of biochemical processes and degeneration of molecular material, however, the mechanisms of diminishing function are not simply a result of aberrant expression of these pathways. Natural selection pressures are at their highest in youthful periods to select genes advantageous to maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene function once beneficial for developmental growth, but pathogenic later in life. Due to this selective ‘shadowing’ in ageing, mechanisms to counter hyperfunctional genes are unlikely to evolve within a given species. These genetic ‘run-on’ programmes are not dysfunctional per se and, in fact, remain highly robust. Thus, interventions capable of optimising gene function during the ageing process represent as attractive therapeutic modalities. Caenorhabditis elegans offers a unique model to explore high-throughput screening of interventions to combat hyperfunctional pathways involved in ageing. However, the majority of research to date employ whole-life vs late-life pathway manipulation of developmental/growth-related systems to claim ageing attenuation, despite significant impairments in early-life fitness and discordance with healthspan. Here, we discuss data supporting hyperfunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutants alter these dynamics. We later discuss the relevance of such mutant models for exploring mechanisms of ageing, highlighting that post-reproductive gene manipulation represents a far more translatable approach for C. elegans research not routed within pleiotropic constraints. More so, lifespan has become a routine readout for quantifying ‘ageing’, however, we make the argument that a compression of gerospan vs lifespan extension is a more meaningful goal for anti-ageing regimes with current knowledge. Similarly, mechanisms governing lifespan are distinct from those regulating health, and slowing senescent pathology accumulation appears more applicable for the abstraction to human ageing.

Individuals with BPD grapple with unstable relationships, marked by extreme emotional swings and interpersonal conflicts. Emotional instability, a distorted self-image, and impulsivity further complicate matters, often leading to self-harm and suicide attempts as desperate coping mechanisms. Genetics and adverse childhood experiences contribute to BPD's development, shaping brain function and emotional regulation. Diagnosis involves meticulous assessments, paving the way for personalized treatments like dialectical behavior therapy and, in severe cases, hospitalization. Early intervention, professional support, and societal understanding are pivotal for positive outcomes, and challenging mental health stigma.

The crayfish plague is a devastating disease of European freshwater crayfish and is caused by the oomycete Aphanomyces astaci (Ap. astaci), which was introduced to Europe around 1860. All European species of freshwater crayfish are susceptible to the disease, including the white-clawed crayfish Austropotamobius pallipes. The aquatic mould is primarily spread by North American crayfish species and can also disperse rapidly through contaminated wet gear moved between water bodies. This spread, coupled with competition from non-indigenous crayfish, has drastically reduced and fragmented native crayfish populations across Europe. Remarkably, the island of Ireland remained free from the crayfish plague pathogen for over 100 years, providing a refuge for A. pallipes. However, this changed in 1987 when a mass mortality event was linked to the pathogen marking the pathogen's introduction to the region. Fortunately, the plague did not establish and was not detected again in Ireland until 2015 when a molecular analysis linked a mass mortality event in the Erne catchment to Ap. astaci. Since then, the pathogen has appeared across the island. Between 2015 and 2023, Ap. astaci was detected in 18 Irish water catchments, revealing multiple genotypes. Intriguingly, the pathogen in Ireland exists without its natural host species. The uneven distribution of various genetic lineages strongly suggests human-mediated transport of zoospores via contaminated water equipment as a primary cause of spread. This review details the timeline of these events, Ap. astaci’s introductions into Ireland, its rapid spread, the genotypes documented, the issue of non-indigenous crayfish species in Ireland and management efforts.

Ureaplasma species (Ureaplasma spp.) are commonly found as commensals in the human urogenital tracts , but their overgrowth can lead to infection in the urogenital tract and at distal sites. Treatment of Ureaplasma spp. infections is difficult. The lack of a cell wall confers resistance to all β-lactam and glycopeptide antibiotics whereas the lack of de novo synthesis of folic acid makes them resistant to sulfonamides and diaminopyrimidines. Thus, there is a need to search for new drugs effective against these bacteria. In the presented studies, the effect of N,N-diethyldithiocarbamate (DDC) at a concentration of 2 µg/ml, 20 µg/ml and 200 µg/ml on the growth and survival of Ureaplasma urealyticum and Ureaplasma parvum was tested. Our results indicated that all DDC concentrations used showed both bacteriostatic and bactericidal activity against both tested strains In brief, for the first time we showed the bacteriostatic and bactericidal activity of DDC against Ureplasma urealyticum and Ureaplasma parvum. Based on literature data, we conclude that this DDC activity is related to the inhibition of urease activity, which is an indispensable enzyme for these bacteria. Further research is needed and the results obtained in the present study should be verified in in vivo models of infection.

O26 enteropathogenic Escherichia coli (EPEC), possesses a unique pseudocapsule composed of polysaccharides identical to the O antigen in their lipopolysaccharide (LPS) membrane. Therefore, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC was investigated. Our findings reveal that the concentration of GlcNAc, an immunodominant unit of O26 polysaccharides capable of activating the MBL (Mannose Biding Lecting) pathway of the complement system, was found to be lower in capsulated EPEC O26 compared to naked shiga toxin-producing E. coli (STEC) O26 strain. It was noted that, unlike the naked STEC strain, the capsulated EPEC O26 strain was protected against lysis by the alternative pathway of the com-plement system by inhibiting C3b adhesion to its bacterial surface. Capsulated EPEC O26 strains were also able to avoid phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies. Additionally, these antibodies were able to recognize O26 EPEC in the presence of biofilm and inhibit their adhesion to human epithelial cells. Overall, the results indicate that the O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the de-velopment of a vaccine against capsulated O26 E. coli

This study provides a comprehensive comparison of the Peter Chew Sum method and Newton's Sum in Quadratic Root Function Computations. Both methods offer significant advancements by alleviating the need for memorization of multiple formulas. However, when confronted with higher-order quadratic root functions such as the calculation of power 33. Newton's Sum method proves cumbersome due to its requirement of all previous answers for final computation, leading to increased steps and error risks. In contrast, the Peter Chew Sum method simplifies the computational process by requiring only a few previous answers, resulting in a more straightforward series of operations. We contextualize our analysis within the historical progression of mathematical techniques, highlighting the transformative leap represented by the Peter Chew Sum method in quadratic root function computations. Peter Chew Sum addressing the limitations of Newton's Sum , especially concerning higher-order functions such as the calculation of power 256. Furthermore, study demonstrates that the innovative approach of the Peter Chew Sum method not only simplifies complex computations but also fosters enhanced conceptual understanding among students. In conclusion, study findings underscore the profound impact of the Peter Chew Sum method on quadratic root function computations.

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.

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.

Ethanolic extracts of propolis collected from Apis mellifera hives have been shown to reduce Nosema ceranae infection in honey bee workers. This study aimed to determine the propolis concentration that optimizes the control of N. ceranae infection in honey bee workers. Newly emerged worker bees were individually fed 2 μL of 50% sucrose solution (w/v) containing 105 N. ceranae spores per bee, and treated with 0%, 25%, 50%, and 75% ethanolic extracted propolis in 50% sucrose solution (v/v). The treated bees were maintained in cages at 34 ± 2˚C and 55 ± 5% RH throughout the study. The number of dead bees was counted and removed from the cages daily for 30 days to generate survival curves. The number of N. ceranae spores per bee (infectivity) was quantified using a hemocytometer, and the number of infected bees per hundred bees (infection rate) was determined. The survival rates of N. ceranae infected bees fed 25%, 50%, and 75% propolis (NP1, NP2, NP3, respectively) were significantly higher than those of infected bees not fed propolis (NO). Furthermore, the infectivity and infection rates of NP2 and NP3 groups were significantly lower than those of the NO group. The infectivity and infection rates of the NP1 group were not different than those of the NO group. Our data suggest that 50% and 75% propolis extracts are appropriate concentrations for treating N. ceranae infection in honey bees. Ethanolic extracted propolis can be an alternative treatment for N. ceranae infection in Western honey bees.

This study developed Makgeolli (Korean traditional alcoholic beverage) by adding raw 20% Codium fragile (Cf), a green seaweed, to a mixed base consisting of rice and oats (1:1 ratio) (COM) and analyzed its quality characteristics and antioxidant activity. The rice based Makgeolli supplemented with raw 20% Cf was designated as control (CRM). The physicochemical (pH, acidity), microbiological (yeast, lactic acid bacteria), antioxidant (DPPH, ABTS), and sensory properties (7-henodonic scale) of CRM and COM were investigated during 7 days of fermentation. The pH/acidity levels of CRM and COM reached 3.66/0.68 and 3.69/0.95 after 7 days of fermentation, respectively. Compared to CRM, COM had lower alcohol and sugar contents (P < 0.05) (CRM: 14.5%/9.8 Brix, COM: 11.2%/7.4 Brix). However, COM contained more yeast and lactic acid bacteria (P < 0.05) (CRM: 1.30/4.28 log, COM: 6.04/6.09 log) compared to CRM. The antioxidant activity of DPPH/ABTS (P < 0.05) in COM was approximately 1.5 times that of CRM (CRM: 40.00/51.57%, COM: 56.76/70.91%). In addition, COM had an excellent sensory preference score (P < 0.05) due to its overall fresh flavor and savory taste (CRM: 4.93, COM: 6.06). Therefore, COM was shown to be Makgeolli with enhanced antioxidant function, with yeast and lactic acid bacteria, and improved flavor, suggesting the possibility of commercializing this Makgeolli.

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

Scholars and policymakers see sustainability as depending on the interrelationships between the three pillars of the environment, society and the economy. However, it remains less clear how key stakeholders with a responsibility for educating the next generation perceive the concept of sustainability and act accordingly. In order to gain new insights, this research scrutinises participant perceptions on sustainability and climate change in two eco-schools in England for primary children (aged 5-11 years). Our case study involved individual interviews with classroom teachers and headteachers, group interviews with fourth- and fifth-year students (ages 10-12 years), and in-class observations. We also analysed data from student exercise books and photographs of school grounds to understand participants’ self-reported knowledge and perceptions of sustainability and climate change. Within a framework drawing on theories of science communication and transformative learning (a learning approach based on having challenging experiences), the results show that the integration of sustainability into the curriculum was limited and problematic. That is despite the fact that all students and teachers were aware of the environmental dimensions of sustainability, like climate change and the overuse of natural sources. These findings suggest that schools are no different to other institutional settings when it comes to dealing with the challenges of integrating sustainability into daily practice. We conclude that there is a need for in-service teacher education programmes to enable and motivate teachers to provide richer teaching-learning environments so as to enable effective learning in schools about sustainability and climate change.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

Background: Atopic dermatitis (AD), a common dermatological condition, is often associated with significant economic and social burdens. Despite extensive studies globally, there is a gap in understanding the comprehensive impact of this condition in Romania. Objectives:This study evaluated the economic burden and quality of life impact of AD in Romania, considering both direct and indirect costs. Materials & Methods: A mixed methods cost of illness study was conducted from April to October 2023. A patient survey, expert reviews, and national health data analysis were used to assess direct medical costs (treatments, medical services), direct non-medical costs (transportation, accommodation), and indirect costs (productivity losses). Quality of life was evaluated using the EuroQol EQ-5D-5L instrument. Results: In 2022, the total cost of atopic dermatitis in Romania was 32.983.498 EUR for adults and 31.573.968 EUR for children. Adult costs included 24.534.603 EUR in direct and 8.429.884 EUR in indirect medical costs, with an average annual cost per patient of 447 EUR. Pediatric costs involved 15.026.781 EUR in direct and 16.516.410 EUR in indirect costs, averaging 290 EUR per patient annually. Conclusion: Care expenditure with AD management in Romania is substantially lower than in other countries, posing a significant economic burden, primarily driven by indirect costs. This study provides a foundation for future policy interventions and highlights the need for targeted management strategies for AD.

Background : Probiotics are composed of microorganisms that have positive effects on health when consumed in prescribed quantities. Lately, studies have attempted to establish this role of probiotics in enhancing health. Aim : The aim of this study was to compare the antifungal activity of 3 different probiotics against Candida albicans.Methodology :This was an in-vitro study. 3 types of commercially available probiotics - Bifilac, Pre pro HS and VSL-3 were cultured separately with Candida albicans and were placed under incubation. The maximum zone of inhibition was recorded for each of the probiotic solutions.Results : In this study, it was found that among the three probiotic products, Bifilac exhibited a maximum zone of inhibition of 13mm at concentration of 100µL against C. albicans, while Pre pro HS and VSL-3 showed zone of inhibition of 11mm at concentrations of 50µL and 100µL, respectively.Conclusion : Within the limits of the present study, This study could prove that probiotics can be considered as an alternative and safe treatment option for treatment of Oral candidiasis infections.

In order to search possible residual minor phases in Y-Ba-Cu-O family, powdered mixtures of Y₂O₃ + BaCO₃ + CuO and, independently, superconducting compound YBa₂Cu₃O_7-x have been treated in evacuated cells and elevated temperatures.YBa₂Cu₃O_7-x was reduced to YBa₂Cu₃O₅ by use of the special home designed Taconis-Knudsen vacuum device. A subsequent doping by oxygen converts produced insulator YBa₂Cu₃O₅ to semiconductor or metal YBa₂Cu₃O_5+x (0<x<0.3). In addition to YBa₂Cu₃O₅, 0.05 volume percent of the minor delafossite phase Y₂Cu₂O₄ was being spotted in the powder mixture 1/2 Y₂O₃ + 2BaCO₃+6Cu₂O, heated up to 818 °C in an inert gas atmosphere. An attempt to prepare the insulating bulk delafossite samples was successful, and subsequent doping by oxygen produces novel metallic phases.

A cell-surface ectonucleotidase CD39 mediates the conversion of extracellular ATP into immunosuppressive adenosine with another ectonucleotidase CD73. The elevated adenosine in the tumor microenvironment (TME) attenuates antitumor immunity, which promotes tumor cell immunologic escape and progression. Anti-CD39 monoclonal antibodies (mAbs), which suppress the enzymatic activity, can be applied to antitumor therapy. Therefore, an understanding of the relationship between the inhibitory activity and epitope of mAbs is important. We previously established an anti-mouse CD39 (mCD39) mAb, C₃₉Mab-1 using the Cell-Based Immunization and Screening (CBIS) method. In this study, we determined the critical epitope of C₃₉Mab-1 using flow cytometry. We performed the PA tag (12 amino acids)-substituted analysis (named PA scanning) and RIEDL tag (5 amino acids)-substituted analysis (named RIEDL scanning) to determine the critical epitope of C₃₉Mab-1 using flow cytometry. By the combination of PA scanning and RIEDL scanning, we identified the conformational epitope, spanning three segments of 275^th to 279^th, 282^nd to 291^st, and 306^th to 323^rd amino acids of mCD39. These analyses would contribute to the identification of the conformational epitope of membrane proteins.

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.

Several methods can be used to evaluate antibody avidity, one of which is the modified ELISA, in which a chaotropic agent is added to disrupt the binding between the antigen and the antibody. Although the avidity index provides relevant information about the functionality of antibodies, it does not allow us to characterize which antigens the antibodies are strongly bound to. To this end, we adapted the Immunoblot and Dot-Blot techniques by adding potassium thiocyanate (KSCN) after incubating nitrocellulose membranes with serum from mice immunized with Neisseria meningitidis outer membrane vesicles (OMVs) or serum from mice immunized with recombinant receptor-binding domain (RBD) of SARS-CoV-2, with different adjuvants for each antigen. In terms of results, when standardizing the incubation time of sera with KSCN, we observed that 5 minutes was the ideal time for both assays, however, when using different dilutions of serum from mice immunized with RBD, there was an influence on the strength of antigen-antibody binding. For the N. meningitidis assay, the antibodies maintained high avidity for the antigens present in the OMVs, PorA, NadA, and Opa, especially in the presence of the aluminum hydroxide adjuvant. The research showed that standardizing the Immunoblot and Dot-Blot in the same assay optimizes time and resources, allowing qualitative analysis for two different antigens, and resulting in more robust information for immunization studies against these pathogens.

Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide-based, glycoconjugate, protein-based and combined conjugate vaccines) that are approved to target five of the six disease-causing serogroups of the pathogen. Immunization strategies have been effective at helping to decrease the global incidence of meningococcal meningitis. Researchers continue to enhance these efforts through discovery of new antigen targets that may lead to a broadly protective vaccine and development of new methods of homogenous vaccine production. This review describes current meningococcal vaccines and discusses some recent research discoveries that may transform vaccine development against N. meningitidis in the future.