The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

Since December 2019, the worldwide spread of COVID-19 has brought the majority of the world to a standstill, affecting daily lives as well as economy. Under these conditions, it is imperative to develop a cure as soon as possible. On account of some of the adverse side effects of the existing conventional drugs, researchers all around the world are screening natural antiviral phytochemicals as potential therapeutic agents against COVID-19. This paper aims to review interactions of some specific phytochemicals with the receptor binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2 and suggest their possible therapeutic applications. Literature search was done based on the wide array of in-silico studies conducted using broad spectrum phytochemicals against SARS-CoV-2 and other viruses. We shortlisted 26 such phytochemicals specifically targeting the S protein and its interactions with host receptors. To validate the previously published results, we also conducted molecular docking using the AutoDockVina application and identified 6 high potential phytochemicals for therapeutic use based on their binding energies. Besides this, availability of these compounds, their mode of action, toxicity data and cost-effectiveness were also taken into consideration. Our review specifically identifies 6 phytochemicals that can be used as potential treatments for COVID-19 based on their availability, toxicology results and low costs of production. However, all these compounds need to be further validated by wet lab experiments and should be approved for clinical use only after appropriate trials.

Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH towards different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g. sulfenylation, S-thiolation, nitrosylation and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.

Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.

Much of the debate on Plan S seems to concentrate on how to make toll access journals open access, taking for granted that existing open access journals are Plan S compliant. We suspected this was not so, and set out to explore this using DOAJ's journal metadata. We conclude that an overwhelmingly large majority of open access journals are not Plan S compliant, and that it is small HSS publishers not charging APCs that are least compliant and will face major challenges with becoming compliant. Plan S need to give special considerations to smaller publishers and/or non-APC-based journals.

Adlay seed samples were collected from 3 adlay growing regions (Yeoncheon, Jeonnam and Eumseong regions) in Korea during 2012. Among all the samples collected, 400 seeds were tested for fungal occurrence by standard blotter and test tube agar methods and different taxonomic groups of fungal genera were detected. The most predominant fungal genera encountered were Fusarium, Phoma, Alternaria, Cladosporium, Curvularia, Cochliobolus and Leptosphaerulina. The occurrence of Fusarium species were 45.6% and based on the combined sequences of two protein coding genes, EF-1a, Beta-tubulin and phylogenetic analysis, 10 species were characterized as F. incarnatum (11.67%), F. kyushense (10.33%), F. fujikuroi (8.67%), F. concentricum (6.00%), F. asiaticum (5.67%), F. graminearum (1.67%), F. miscanthi (0.67%), F. polyphialidiom (0.33%), F. armeniacum (0.33%) and F. thapsinum (0.33%). The ability of these isolates to produce mycotoxins fumonisin (FUM) and zeralenone (ZEN) were tested by ELISA quantitative analysis method. The result revealed that fumonisin (FUM) was produced only by F. fujikuroi and zeralenone (ZEN) by F. asiaticum & F. graminearum. Mycotoxigenic species were then examined for their morphological characteristics to confirm their identity. Morphological observations of the species correlated well with their molecular identification and confirmed as F. asiaticum, F. fujikuroi and F. graminearum.

Parkinson’s disease (PD) is the second most common degenerative disease which may cause blood pressure abnormalities due to autonomic dysfunction. Early morning rise of blood pressure which is called morning surge is found to be related with some cardiovascular diseases when it is exaggerated. We wanted to search the relation of Morning blood pressure surge (MBPS) and inflammation in PD. Method: Ambulatory blood pressure monitoring for 24 hours, fibrinogen to albumin ratio, hs-CRP are used in this retrospective study. Fifty idiopathic PD patients and 50 age and sex matched control cases were included. MBPS, it has been defined as the difference between morning BP (measured 2 hours after awakening) and the lowest night-time BP. Body mass index (BMI) is used as an independent variable. Results: Median value of MBPS for PD group (21,63) was significantly different from the control group values (18,63) (p

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

With the increasing occurrence of rotator cuff injuries every year, there is a great need for a reliable treatment option. Wharton’s Jelly contains several components that can positively impact the replacement and repair of musculoskeletal defects. The overall objective of this study is to evaluate the improvement of patient-reported pain scales after applying Wharton’s Jelly (WJ) in rotator cuff defects. Eighty-seven patients with rotator cuff defects who failed at least eight weeks of conservative treatment were selected from the retrospective repository. 2cc of WJ flowable allograft was applied to the specific affected anatomy, the most common being supraspinatus tendon, biceps tendon insertion, labral tear, and subscapularis tear. No adverse reactions were reported. Statistically significant improvements were found from the initial to Day 90 in all scales. Patient satisfaction was calculated using minimal clinically important differences. No statistically significant differences were found in mean changes between gender, BMI, and age. Scanning Electron Microscopy images reveal the similarities between the collagen matrix in WJ and the rotator cuff. The significant improvement in patient outcomes coincides with current literature analyzing WJ applications with other structural defects around the body. WJ is a promising alternative for musculoskeletal defects when the standard of care fails.

Cow’s Milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, 'lactase deficient' individuals cannot digest milk's carbohydrate lactose depriving themselves of highly beneficial milk proteins like casein, lactoalbumin and lactoglobulin, due to lactose intolerance (LI), while other individuals develop cow milk allergy specifically against these proteins (CMPA). The management of these conditions is distinctly different and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restriction or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of the nutrients over the genome, proteome and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and so increasing life expectancy. Here, we report the scientific community opinion proposing to replace the approach “one size fits all” with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety, often resulting from the individual perception of this condition as different from a normal state.

This research proposes an algorithm to sign messages using the ElGamal asymmetric cryptosystem, called: Digital signature algorithm based on ElGamal, Diffie-Hellman protocol and the number π (DSAπ). This proposal has a high level of security like the DSA standard, in addition, execution times are reduced in relation to it. The Diffie-Hellman protocol and the number π were used in the construction of the digital signature algorithm in conjunction with the Hash-Sha-512 function. Some experiments are presented to provide evidence that the bits on the right side of the decimal point of π appear randomly, such as: a color image was constructed of a string of consecutive bits chosen at random, of the number π. Subsequently, parameters such as: entropy, correlation, discrete Fourier transform, goodness-of-fit test χ2 were evaluated. It is mentioned that an S-box 8×8 is involved in the signature. The sensitivity of the signature was measured, that is, when small changes are made to the sender’s private key, or small changes to the message. Finally, an image was constructed using the signatures of random texts, and subsequently the randomness of its pixels was obtained, to verify that there is no relationship between the different signatures.

Intrusion detection is generally carried out by matching network traffic patterns with known attack patterns or by identifying abnormal network traffic patterns. One statistical methodological approach used in intrusion detection is Statistical Process Control (SPC) by constructing a control chart. Hotelling’s T2 control chart is a multivariate control chart commonly used to monitor the mean process. The performance of the T2 chart in monitoring mean shifts can be increased if a robust estimator is utilized. Based on previous research, T2 based on the Fast-MCD estimator has good performance in monitoring low to medium outlier contaminated data. Therefore, the MRCD estimator can be used to detect intrusion. On the other hand, this research focuses on developing a bootstrap-based robust Hotelling’s T2 charts with Fast-MCD and MRCD estimators for evaluating performance in detecting intrusion on intrusion detection datasets. Based application of UNSW-NB15, the proposed chart has better performance than the conventional T2 and Fast-MCD-based T2 despite the longer execution time.

The Sidi Bou Othmane (SBO) pegmatite district is in the Central Jebilet massif, Occidental Meseta domain, Morocco. The SBO district is hosted essentially in a volcano-sedimentary series composed of the Late-Devonian Sarhlef shales. Pegmatite bodies crop out as dykes, which are oriented from N-S to E-W and are generally variably deformed with ductile and/or brittle structures with ante, syn- or post kinematic criteria. Petrographic observations of pegmatite dykes show that feldspars (i.e., albite, microcline) are the most abundant mineral phases, followed by quartz, micas, with tourmaline and accessory mineral as garnet, and zircon and secondary minerals as clinochlore, sericite, and illite. The geochemical study indicates that, according to the major pegmatite elements dykes of SBO have mainly a S-type granitic composition and are peraluminous granite with calc-alkalic affinity. The study of trace elements pointed out that SBO pegmatite formed under post-orogenic syn-collision context during the Variscan orogeny, by the partial melting of argilliferous sediment and can be ascribed to the muscovite-bearing pegmatite; moreover, they have a good potential on ceramic and contain minerals, such as feldspar, recently assessed as Critical raw materials by European Union.

The work is devoted to the development of methods for constructing asymptotic formulas as x→∞ of a fundamental system of solutions of linear differential equations generated by a symmetric two-term differential expression of odd order. The coefficients of the differential expression belong to classes of functions that allow oscillation (for example, those that do not satisfy the classical Titchmarsh-Levitan regularity conditions). As a model equation, the 5th order equation i2p(x)y′′′′′+p(x)y′′′′′+q(x)y=λy, for which various cases of behavior of the coefficients p(x),q(x), is investigated. New asymptotic formulas are obtained for the case when the function h(x)=−1+p−1/2(x)∉L1[1,∞) significantly influences the asymptotics of solutions to the equation. The case when the equation contains a nontrivial bifurcation parameter is studied.

It is important to develop new antibacterial drugs since the emergence of bacterial resistance to available antibiotics. Metal nanoparticles have the potential to combat antibiotic resistance and are effective antibacterial agents. Here, we demonstrate the biogenic production of zinc nanoparticles using Rhododendron arboreum stem bark. The biosynthesized ZnNPs were characterized through different analytical techniques such as UV-vis, FTIR, EDX, SEM, and XRD. Clinical isolates such as E. coli, S. aureus, and K. pneumonia were used to check the antibacterial efficacy of the biosynthesized zinc nanoparticles. The MIC and MBC values against K. pneumonia, S. aureu, and E. coli were found to be 34±0.21 and 11.71±0.47, 47±0.11 and 23.86±0.84 and 94±0.18 and 40.43±0.16 µg/mL, respectively. It dramatically decreased the integrity of the cell membrane and markedly increased the permeability of both inner and outer membranes. The green synthesized ZnNPs have good catalytic activity. It degraded 65% of methyl orange dye within 6h when the mixture was kept in direct sunlight, thus demonstrating good photodegradation potential and can be employed as a good photocatalyst. According to these results, biosynthesized zinc nanoparticles could be a potential therapy option for controlling bacterial pathogenesis and an effective photocatalyst for the elimination of hazardous water contaminants.

Following on from work already carried out in our laboratory on a new biomass-derived green solvent, eucalyptol, we are now turning our attention to sabinene as a new green solvent. Sabinene is also derived from biomass. We have shown that it can be used as such or distilled to synthesize thiazolo[5,4-b]pyridine heterocycles by thermal or microwave activation. This new solvent was compared with various conventional and green solvents. The conditions were optimized to enable us to carry out the syntheses in good yields, and we were able to show that sabinene, a natural bicyclic monoterpene, could be used effectively as a solvent.

Perinatal stress experienced by mothers of very premature newborns may influence the mother’s milk and the infant’s intestinal microbiota. This prospective study of mothers of very preterm infants fed with mother´s own milk (MOM) was carried out in a tertiary hospital over a 2-year period. Assessment of maternal stress in 45 mothers of 52 very preterm newborns using the parental stress scale (PSS:NICU) that revealed an inverse relationship between stress and MOM production in the first days of life (p=0.012). The greatest contributor to stress was the one related to the establishment of mother-child bond. Maternal stress was lower in mothers in whom the kangaroo method was established early (p=0.011) and in those with a higher educational level (p=0.032). Levels of fecal calprotectin (FC) decrease with the passage of days and were directly correlated with birthweight (p=0.044). FC levels 7 days post-delivery were lower in newborns that received postnatal antibiotics (p=0.027). High levels of maternal stress resulted in progressive decreases and increases in the proportions of Firmicutes and Proteobacteria species, respectively, over 15 days post-delivery, both in MOM and in fecal samples from premature newborns. These findings underscore the importance of recognizing and appropriately managing maternal stress in neonatal units, given its marked influence on both the microbiota of maternal milk and the intestinal microbiota of premature newborns.

Currently, a wide variety of velocity profiles are used in motion control. Thus, this paper compares the energy consumption of three parabolic, trapezoidal, and S-curve profiles. We studied the case of using embedded systems since they are a powerful solution to monitor and coordinate the movement of devices and machinery in various industries combined with motion control applications. These integrated systems allow precise and efficient control of motors and actuators through control and feedback algorithms. In addition, we propose an alternative methodology for implementing motion controllers using an Advanced RISC Machine (ARM) microcontroller, which computes the trajectory and the control action in real-time. We conducted an experiment using a linear plant composed of a direct current (DC) motor coupled to an endless screw where a carriage is mounted that can move mechanically along a rail a distance of 1.16m. In addition, a 4096 pulses per revolution (PPR) encoder is connected to the motor to measure position and angular velocity, which compute the distance the carriage has moved in meters. A current sensor is used to assess the energy consumption, and 40 tests for each profile were carried out to compare the energy consumption for the three-motion profiles considering cases with and without load on the carriage.

A simulation test system for the two-dimensional (2D) fuze overload loading process was designed to address the loading issues of recoil overload and centrifugal overload in fuze safety and arming (S&A) devices. By incorporating centrifuge rotation energy storage, impact acceleration simulation, and equivalent centrifugal rotation simulation, a block equipped with a fuze S&A device was accelerated instantly upon being impacted by a centrifuge-driven impact hammer, simulating recoil overload loading. The impact hammer was retracted instantaneously by adopting an electromagnetic brake, which resulted in the centrifugal rotation of the block around its track, to simulate the centrifugal overload loading. The dynamic equations of the simulation test system and the equations of impact hammer motions were established, whereby the rotation speed of the centrifuge and the braking force of the electromagnetic brake were calculated and selected. A dynamic model of the collision between the impact hammer and block was established using ANSYS/LS-DYNA software for simulation analysis. The acceleration curves of the recoil overload and centrifugal overload with variations in the centrifuge speed, cushion material, and buffer thickness were obtained, which verified the feasibility of the proposed loading simulation method. 2D overload loading simulation tests were performed using the developed simulation system, and the acceleration curves of the recoil overload and centrifugal overload were measured. The test results indicated that the proposed system can accomplish 2D overload loading simulations for a recoil overload of several 10000 g and centrifugal overload of several 1000 g.

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency i.e. 5.13±0.10% and 82.36±4.01%, respectively. SC PLGA NPs showed a spherical morphology on an average size (134.8±4.61nm), PDI: 0.277±0.004, and −25.3±1.03mV zeta-potential is suitable for oral delivery. Development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameters examinations with 1.219-minutes RT, MS (162.00/73.10), and a total run-time was 2.0-minutes. 1.0–1000.0ng/mL was a linear-range with inter & intra-day accuracy (92.55–99.40%) followed by precision (1.88–4.23%). SC PLGA NPs oral bioavailability was significantly higher (**p<0.01) as compared to SC-S treated groups (iv & oral). We found that the antimicrobial activity of SC PLGA NPs was more effective than pure S-Allyl-L-Cysteine with significant results (p<0.01) as compared to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties which can be helpful for oral administration. On the basis of our observations, SC PLGA NPs suggested the highest potential for the improvement of oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and is the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described, a clinical isolate infection model, utilizing isolates obtained from patients with CF, an incomplete antibiotic clearance model, leading to bacterial bounce-back and the establishment of chronic infection, and an adapted water bottle chronic infection model. These models circumvent the requirement for surgical procedure and importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.

The research is a deep study of the CBOE Volatility Index (VIX), which represent the market sentiments of the S & P 500 Index (SPX) over a period of 33 years. It evaluates how the two indexes perform in the stock market crash and how reliable VIX is in predicting market sentiments. The research distributes the market rally in two forms, and one is a trust rally, when investors are happy to see the market in a stable form, and investors' sentiments are positive towards the stock market. Second is a fear rally, where investors' sentiments are negative, and their outlook is bearish for various reasons. It observes the pattern of rallies, like the longest trust or fear rally, in which year and its duration. The research analyzes data to reach a meaningful conclusion and various inferences that can be drawn from the study of historical data.

Methyl Salicylate (MS), the principal constituent of Wintergreen oil (WO) was obtained from acetyl salicylic acid (ASA) by sequential transesterification-esterification reaction promoted by NbCl5for the first time. The reagents were added simultaneously, and the reaction process involved the transesterification and esterification reactions, which were accompanied by thin layer chromatography and gas chromatography. The conversion rate via GC was 100%, and the MS yield was 94%. A cytotoxicity of 50% and 64% for cultured S. aureus and metastatic melanoma cells, respectively, was observed for a concentration of 0.6 mg/mL, whereas no cytotoxicity for non-tumor cells was observed for this concentration, and it is considered to be the optimum concentration.

In response to the new concept of the impact of total climate production factors on plant phenology, this study will verify the feasibility of simulating plant phenology and triggering thresholds based on total climatic production factors by using the phenological and meteorological observation data of S. krylovii plant from 1985 to 2018 at the Xilinhot National Climate Observatory of China Meteorological Administration. The results indicate that the total climate production factors influencing plant phenological changes can be well used for phenological simulation and its triggering thresholds. The mutation of cumulative climate production potential based on total climate production factors can effectively indicate the green-up date and the wilting date of S. krylovii plant, and their triggering thresholds depend on the parameters of climate resource change and plant biology, which are (0.085, –5.363) and (0.086, –27.620), respectively. The cumulative climate production potential based on total climate production factors can effectively indicate the heading date of S. krylovii plant, and its triggering thresholds also depends on the parameters of climate resource change and plant biology, which is (394.632，–38026.268). Furthermore, the results support the viewpoint that the climate abrupt changes determine the beginning and the ending of plant growth, while the accumulative climate resources determine the other phenological dates. This study provides new ideas for the study of plant phenology.

With the explosion of the generation, transmission and sharing of image data over the Internet and other unsecured networks, the need and significance for the development of novel image encryption algorithms is unprecedented. In this research work, we propose a novel framework for image encryption that is based on two hyperchaotic maps, utilized in conjunction with the single neuron model (SNM). The framework entails three successive stages, where in every stage, a substitution box (S-box) is applied, then XORing with an encryption key is carried out. The S-boxes and the encryption keys are generated from the numerical solutions of the hyperchaotic maps and the SNM. The performance of the proposed framework is gauged through a number of metrics, reflecting superior performance and complete asymmetry between the plain images and their encrypted versions. However, the main advantages of this work are: (1) The attained width of the key space; and (2) The achieved efficiency in software implementation. The superior key space of 2^{2551} is the result of employing the two hyperchaotic maps, while the improved efficiency, resulting in an average encryption rate of 8.54 Mbps, is the result of the utilization of the single neuron model, as well as the employment of optimized parallel processing techniques. In addition, the proposed encryption framework is shown to output encrypted images that pass the NIST SP 800 suite.

From the merge of arts and crafts towards a practice for mass production of desirability, consumption and product development in a capitalist economy of scale, design has lost its natural ability of problem comprehension and tension alleviation. The modern world needs the creativity, flexibility, and responsiveness embedded into design practices, mostly when a behavioural change, either individual or organizational, is intended. Still, the informality nature of the field is creating a gap between the study, research, and industrial design practice. Here it is presented the Biology of Creativity Model (BoC) which is a design-by-analogy method that promotes an empowered design practice through analysis of mostly biology reference texts for enhanced creativity and innovation performance in a diverse array of contexts.

Cotton is one of the most important economic crops in the world, whereas insect attacks is a prime cause of its losses on yield and quality. Despite it is important, little is known about the mechanism of cotton response to insect. In this study, we simulated insect feeding by applying insect oral secretions (OS) to wounds, and combined transcriptome and metabolome analysis to comprehensively investigate how OS from two major pest species (Helicoverpa armigera and Spodoptera litura) affect cotton defense responses. Obvious differences were observed that 12,668 and 13,379 genes differently expressed respectively in cotton after being treated with different OS when compared with wounding along. Upon the addition of OS, JA-signaling pathway were rapidly and strongly induced, however SA-biosynthesis related gens were significantly down-regulated. By constructing the co-expression gene network, we identified a hub gene which encoding a leucine-rich repeat receptor kinase may play important role in recognition and signal transduction at early stage. We also found that OS from different insect species altered abundance of flavonoid related compound with different patterns. Interestingly, Gossypol which is a well-known anti-insect compound was kept a relative low content after OS application relative to wounding which implied the existence of the suppression effects of OS to cotton defense response. This study illustrated the transcriptional and metabolic changes of cotton in responding to OS from two chewing insect species, identified potential key gene during the interaction process and finds the evidence for OS’s inhibition effects on cotton defense response.

In this paper, we introduced many new notions and new contraction named as S-weakly contraction after that we obtained the p-common best proximity point theorems for different types of contractions in the setting of complete metric spaces by using weak P_p-property and proved the uniqueness of these points. Also we presented some examples to prove the validity of our results.

Amidst worsening climate change, drought stress imperils global agriculture, jeopardizing crop yields and food security, necessitating urgent exploration of sustainable methods like biopriming, harnessing beneficial microorganisms to bolster plant resilience. Recent research has revealed diverse biological compounds with versatile applications produced by Schizophyllum commune, rendering this fungus as a promising contender for biopriming applications. For the first time this study aimed to investigate,the potential of S. commune exo- (EPSH) and intra-PSH (IPSH), isolated from two strains: Italian (ITA) and Serbian (SRB) under submerged cultivation, in enhancing the resilience of Pisum sativum L. seeds through biopriming technique. Testing of seed quality of bioprimed, hydroprimed, and unprimed seeds was done using a germination test, under optimal and drought conditions. In optimal conditions, the IPSH SRB increased germination energy by 5.50% compared to the control, while the highest percentage of germination (94.70%) was shown after biopriming with PSH isolated from the ITA strain. Additionally, all assessed treatments resulted in a boost in seedling growth and biomass accumulation, where the ITA strain demonstrated greater effectiveness in optimal conditions, whereas the SRB strain showed superiority in drought conditions. The drought tolerance indices increased significantly in response to all examined treatments during the drought, with EPSH ITA (23.00%) and EPSH SRB (24.00%) demonstrating the greatest effects. Results demonstrate a significant positive influence of fungal PSH, indicating their potential as biopriming agents and offers insights into novel strategies for agricultural resilience in the face of changing environmental conditions.

A difficult open problem that has never been fully resolved in the literature to date is the behaviour of the (TDCDP) third approximation. As a giant step towards modern control theory, this cutting-edge paper will advance control theory and other relevant inter-disciplinary subjects. Because control theory is important in industry and engineering, this study will be especially beneficial to anyone working in these disciplines who wish to understand more about recent advances in control theory settings. In contrast, the wealth of applications of Fokker Planck Kolmogorov (FPK) equations numerous disciplines As a result, the study instantly gains more taste and credibility. At the end of the paper, there are several challenging open problems, some concluding remarks, and recommendations for further investigation.

Our starting point is the covariant coordinate transformation equation of a relativistic positioning system in Minkowski space-time, which maps the receiver’s emission coordinates (proper times broadcast by the emitters) to its coordinates in some inertial reference frame. Bancroft’s analytical (closed-form) solution to the basic pseudorange navigation equations with four emitters is recovered and the subjacent elements are geometrically interpreted. The case of four static beacons is analized as a clarifying situation.

This article addresses the urbanization model in valley bottom areas in the city of São Paulo, an-alyzed in its urban planning and socio-environmental aspects, and examines the hydrological impacts triggered by its implementation. It argues that sustainable occupation of urbanized hy-drographic basins should be based on environmental criteria in order to attain a sustainable water management regime that can ensure urban and environmental resilience. In the “Introduction,” the article emphasizes that urbanization in São Paulo has neglected the natural features of river basins, promoting the channeling of watercourses, which resulted in floods and inundations. “Theoretical Basics” brings in key concepts related to the environmental approach of drainage infrastructure with gray and green-blue systems. “Methods” details our qualitative research, bibliographical analyzes, referential case studies, and cartographical analyzes (geoprocessing), focusing on a case study in the Jaguaré creek basin. “Results” includes guidelines and recom-mendations for an urbanization model adjusted to valley bottom areas, applicable to new patterns of urban occupation or to the adjustment of existing patterns. “Discussion” explores the concept of “local sustainable self-development,” and “Conclusions” highlights the importance of an inte-grated, multisectoral, and sustainable planning, adjusted to the characteristics of river basins in valley bottom areas, promoting a socially responsible urban occupation, especially in the face of climate change.

. Interconnected control systems (ICS) widely apply to various technical systems. ICS has a complex description. Therefore, simplified models use, which the specifics of an object do not always reflect. So, the problem of synthesizing mathematical models is topical. The work purpose is to develop an approach to obtaining models in conditions of incomplete a priori information. We use an adaptive approach. As examples, two-channel systems (TCS) with cross-links and identical channels consider, and a method for mathematical model design. We consider the system with asymmetric cross-links and evaluate their impact on properties of an adaptive identification system. Approach proposed to assessing the TCS identifiability with cross-links. The excitation constancy influence on TСS parameter estimates is studied. A generalization of the proposed approach is given for an interconnected system.

Smoker’s paradox usually refers to the common observation of a favourable outcome of smoker patients in acute myocardial infarction. The interpretation of this phenomenon is still controversial and not fully explained. We aimed at assessing whether smoking could be associated with mortality in a large cohort of prospectively enrolled patients with ST segment elevation myocardial infarction (STEMI) referred to primary percutaneous coronary intervention (pPCI). From April 2006 to December 2018 a population of 2456 STEMI patients treated with primary PCI were prospectively enrolled in the MATRIX registry. Ischemic time, clinical, demographics, angiographic data and 1-year follow-up were collected. Among 2546 patients admitted with STEMI 1007 (41%) were current smokers. Smokers were 10 years younger and had lower crude in-hospital and 1-year mortality (1.5% vs 6%, p&lt;0.0001 and 5% vs 11%, p&lt;0.0001), shorter ischemic time (203 [147-299] vs 220 [154-334] minutes, p=0.002) and shorter decision time (60 [30-135] vs 70 [36-170] minutes, p=0.0063). After propensity-matching, age, cardiogenic shock and low TIMI score were associated with in-hospital mortality, while smoking habit was still associated with reduced mortality. Smoking was also associated with reduced death rate at 1-year follow-up (HR 0.54, 95% CI [0.37 - 0.78]; p&lt;0.001). Our data show a protective link between smoking status and mortality in patients with STEMI, the so called “smoker’s paradox”. This could be explained not only by the shorter ischemic time and younger age of the smoking population but also by a specific pathogenetic effect of smoking underlying the onset of STEMI and response to therapies.

Any malocclusion can be associated with various face development patterns, including hyper, neutral and hypodivergent growth patterns. We measured face height ratios, angle formed by Y axis to SN and growth patterns in various malocclusions in a group of patients from Timis county. The pretreatment digital cephalograms of 350 participants were split into three groups based on Angle's classification of dentoalveolar malocclusion. Every cephalogram was digitally traced and analyzed using a composite cephalometric method analysis utilizing the WebCeph imaging cephalometric program, which included two linear and one angular. In general, patients from Timis county have a hypodivergent development pattern. Hypodivergent development pattern predominated in group I, II, and III. Group I hyperdivergent 5.14%, normodivergent 16.01%, hypodivergent 78.85%. Group II hyperdivergent 2.78%, normodivergent 14.44%, hypodivergent 82.78%. Group III hyperdivergent 10.53%, normodivergent 10.53%, hypodivergent 78.94%. In all three groups, the value of the angle formed by Y axis to SN is within normal limits group I 65.4 ±4.34°, group II 63.87± 3.86° and group III 64.66 ±5.28°. A strong negative correlation was found between angle: Y axis to SN and facial height ratio (r= -0,766; p &lt;0.001). In all kinds of malocclusion, patients from Timis county show primarily a hypodivergent development pattern.

Nowadays, it is highly desired to develop highly active and humidity resistive ozone decomposition catalyst to eliminate the ozone contaminant, one of the primary pollutants in air. In this work, a series of Cu2S hollow structured materials are rapidly synthesized using different structured Cu2O templates. The Cu2S from porous Cu2O shows the highest ozone catalytic decomposition efficiency of >95% to 400 ppm ozone with a weight hourly space velocity of 480,000 cm3g-1h-1 in dry air. Importantly, the conversion still keeps >85% in a high relative humidity of 90%. The mechanism is explored by diffusive reflectance infrared spectroscopy which shows the decomposition intermediate of O22-, and the X-ray photoelectron spectroscopy reveals the dual active site of both Cu and S. All these results show the effective decomposition of ozone by Cu2S especially in harsh environments, promising for active ozone elimination.

Background: Parkinson's disease (PD) is a global disease. However, there is a lack of research specifically focused on the AfrAbia population. Climate change, driven mainly by global warming, is linked to detrimental health impacts, including an increased frequency and intensity of heat waves. Neurological diseases, including neurodegenerative syndromes like Alzheimer's disease, Parkinson's disease, and motor neuron illnesses, have been increasingly seen and recorded in scientific literature. Although there is much literature demonstrating the growth in neurodegenerative disorders, the relationship between environmental variables such as global warming, air pollution, heavy metals, and pesticides and the higher occurrence of these illnesses is still unknown. Objective: The current article primarily aims to examine the relationship between climatic changes, air pollution, pesticides, heavy metals, and the occurrence of PD. Initially, we evaluate the influence of exposure to these variables on the cause or origin of Parkinson's disease. In addition, we will investigate how these variables disrupt processes such as excitotoxicity, oxidative stress, and neuroinflammation, all of which are strongly linked to Parkinson's disease (PD). Conclusions: This research presents a plausible rationale for the adverse effects of environmental influences on the brain, which are pivotal in the progression or onset of Parkinson's disease from an AfrAbian standpoint.

The early detection of cognitive decline and timely non-pharmacological management or drug therapy are extremely important in providing care for Parkinson’s disease with dementia (PDD). In this study, we first conducted a discovery study to identify six plasma microRNAs that may allow for the differentiation of PD with or without mild cognitive impairment via NGS. A total of 120 participants were further recruited in a validation cohort and divided into four subgroups, namely, normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI) and PDD. Among the six candidates, miR-203a-3p was successfully detected in the plasma of the validation cohort using droplet digital PCR (ddPCR). Our results show that the ratio of miR-203a-3p/miR-16-5p observed in PDD was significantly increased compared to in PD-MCI (p < 0.001) and PDND (p = 0.041). Moreover, the ratio of miR-203a-3p/miR-16-5p showed a significant correlation with MoCA scores (r = -0.237, p = 0.024) in patients with PD (PwP). The ROC curve of the logistic regression model, consisting of the variables of age, the ratio of miR-203a-3p/miR-16-5p and the UPDRS III score, also demonstrated an average AUC of 0.883 via 5-fold cross-validation. In conclusion, the ratio of miR-203a-3p/miR-16-5p may serve as a potential biomarker for distinguishing cognitive dysfunction from PwP.

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

As humans age, aberrancies in several signaling pathways occur. In the aging population, some patients display abnormal bone morphogenetic protein (BMP) signaling. This can lead to osteoporosis (OP), a debilitating bone disorder caused by an imbalance between osteoblasts and osteoclasts. In 2002, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery as it is crucial for bone formation. However, complications have been reported with rhBMP-2 and primary osteoblasts isolated from OP patients are unresponsive to BMP-2. While patient samples are available, previous medical history may alter results. Therefore, C57BL/6 mice, an aging model that displays aberrant BMP-signaling, can be utilized to investigate OP and aging. We show that BMP receptor type Ia (BMPRIa) is upregulated in the bone marrow stromal cells (BMSCs) of 15-month mice similar to previous data. We show that a conjugation between BMP-2 and Quantum Dots (QDot®s) effectively binds to BMPRIa and can investigate BMP-2 activity. After incubating BMSCs with methyl-β-cyclodextrin (MβCD), BMP-signaling is restored in 15-month mice as shown by western blotting and the von Kossa assay. MβCD may be used to rescue BMPRIa and the BMP-signaling pathway can be utilized by future therapeutics to treat OP.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

This article is a study on the (k,s)-Riemann-Liouville fractional integral, a generalization of the Riemann-Liouville fractional integral. Firstly, we introduce several properties of the extended integral of continuous functions. Furthermore, we make the estimation of the Box dimension of the graph of continuous functions after the extended integral. It presents that the upper Box dimension of the (k,s)-Riemann-Liouville fractional integral for any continuous functions is no more than the upper Box dimension of the functions on the unit interval I=[0,1], which indicates that the upper Box dimension of the integrand f(x) will not be increased by the σ-order (k,s)-Riemann-Liouville fractional integral ksD−σf(x) where σ&gt;0 on I. Additionally, we prove that the fractal dimension of ksD−σf(x) of one-dimensional continuous functions f(x) is still one.

Hemoglobin is one of the proteins that are more susceptible to S-glutathionylation and the levels of its modified form, glutathionyl hemoglobin, increase in several human pathological conditions. The scope of the present review is to provide knowledge about how hemoglobin is subjected to be S-glutathionylated and how this modification affects its functionality. The different diseases that showed increased levels of glutathionyl hemoglobin and the methods used for its quantification in clinical investigations will be also outlined. Since there is a growing need for precise and reliable methods of markers of oxidative stress in human blood, this review highlights how glutathionyl hemoglobin is more and more emerging as a good indicator of severe oxidative stress but also as a key pathogenic factor in several diseases.

The structural identification (SI) problem of control objects has not been solved. The formalization and interpretation complexity of the structure concept is the main problem. In identification systems, the form of the model (its structure) choice is intuitive and bases on the experience and knowledge of the researcher in most cases. The task of parametric identification is often interpreted as SI. It introduces certain confusion in understanding of the task and decision-making. This is two different areas of research. The structural identification problem is multifaceted and includes many subtasks, and their solution gives the final result. Some tasks have been solved. The purpose of this work is to review existing approaches and methods to the structural identification problem of control objects from a system perspective. It is necessary to give the SI problem statement at the multiple-informational level to reflect the difficulties of formalizing SI. New directions to analyse that were not SI areas until now.

Histidine is an essential amino acid with significant implications in human growth and neuromodulation. Its concentration within cells, when either elevated or reduced, can indicate different diseases. While various methods exist to measure increased histidine levels, there remains a significant lack of sensors capable of actively responding to histidine deficiency within cells and releasing strong signals. In this study, we exploited the high induction levels of the his operon in S. Typhimurium SL1344, a histidine auxotroph, within a histidine-deficient environment, to develop a specific bacterial sensor with sensitivity towards low histidine concentrations. The SL1344-pGEX sensor, with a high copy number, exhibited remarkable sensitivity and selectivity to histidine in the range of 0 to 50 μM. Notably, even a minute addition of histidine (approximately 2.5 μM) to the M9 medium led to observable fluorescence reduction, rendering it highly suitable for monitoring histidine-deficient cellular environments. This bacterial fluorescence sensor holds great potential for detecting changes in intracellular histidine concentrations during pathogenic bacterial infections and for assessing the impact of drugs on cellular metabolism.

Background: Alzheimer's disease causes great changes, with the prefrontal cortex be-ing frequently damaged zones, affecting physical and cognitive behavioural and compromising autonomy and quality of life. Objective: To evaluate the effectiveness of feedback-based tech-nology on the improvement of physical-cognitive capacities in Alzheimer. Methods: Forty pa-tients with Alzheimer were recruited from the Santa Elena Alzheimer's Association, Seville, of which 15 ended up being pilot participants, divided randomly into controls (8) and experi-mental (7). They were evaluated with: Cognitive Mini-Examination Scale, Oddball Test and At-tention Network, Berg Scale, Tinetti, Timed up and Go and Geriatric Deterioration Scale. The experimental group was treated with feedback-based technology under the supervision of physiotherapists, during 16 thirty-minute sessions, twice a week. The control group performed their usual care. Result: A significant improvement was observed in the experimental group (Cognitive Mini-Examination and Tinetti). In the group of control, a worsening of physical and motor skills was evidenced because of the degenerative disease. Discussion/Conclusion: This treatment could be a strategy to keep the patient in early stages for longer, and improve quali-ty of life delaying dependency. It creates intergenerational bonds and use at home to promote treatment adherence.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p &gt; 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p &lt; 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

Magnetic and morphological properties of equiatomic B2-ordered FeRh thin films irradiated with single high-intensity ultrashort laser pulses are investigated. The goal is to elucidate the effect of femtosecond laser ablation on the magnetic properties of FeRh. We employed Scanning Magneto-Optical Kerr Effect (S-MOKE) microscopy to examine the magnetic phase after laser processing, providing high spatial resolution and sensitivity. Our results revealed the appearance of a magneto-optical signal from the bottom of ablation craters, suggesting a transition from antiferromagnetic to ferromagnetic behavior. Fluence-resolved measurements clearly demonstrate that the ablation threshold coincides with the threshold of the antiferromagnet-to-ferromagnet phase transition. The existence of such magnetic phase transition was independently confirmed by temperature-dependent S-MOKE measurements using a CW laser as a localized heat source. Whereas the initial FeRh film displayed a reversible antiferromagnet-ferromagnet phase transition, the laser-ablated structures exhibited irreversible changes in their magnetic properties. This comprehensive analysis revealed the strong correlation between the femtosecond laser ablation process and the magnetic phase transformation in FeRh thin films.

Biofilm formation is important in the free-living and symbiotic lifestyles of Sinorhizobium meliloti. Here we show that the S. meliloti NspS-MbaA system is homologous to the c-di-GMP modulating NspS-MbaA system described in Vibrio cholerae and modulates biofilm formation, exopolysaccharide (EPS) production and motility in S. meliloti in response to exogenous polyamines. Biofilm and EPS production in quorum sensing-deficient wild type strain 1021 decreased in cultures containing putrescine, 1,3-diaminopropane or spermine, but were unaffected in a 1021 nspS mutant (1021 nspS). Decreases in biofilm formation caused by these polyamines paralleled decreases in EPS production and increases in nspS transcription. Cell aggregation did not differ markedly between strain 1021 and 1021 nspS. The S. meliloti quorum sensing-proficient Rm8530 wild type strain and nspS mutant (Rm8530 nspS) produced similar levels of biofilm under control conditions and 3.2- and 2.2-fold more biofilm in cultures with norspermidine, but these changes did not correlate with EPS production. Rm8530 nspS aggregated up to several fold more than the wild type under most conditions. Changes caused by polyamines in swimming and swarming motility were not generally dependent on NspS-MbaA in either 1021 or Rm8530. We speculate that the S. meliloti NspS-MbaA system could modulate biofilm formation in response to environmental polyamines.

Background: Insecticide resistance in Anopheles gambiae s.l. is a major challenge for malaria vector control in Nigeria. Both target-site insensitivity and metabolic resistance have been im-plicated in resistance process, with the latter receiving little attention in Nigeria. Therefore, we investigated metabolic enzyme activities in Anopheles gambiae s.l populations resistant to Del-tamethrin and Diethyldichlorotriethylethane (DDT) in South-West Nigeria. Methods: Anopheles larvae were collected from Ibadan, Oyo and Badagry, Lagos. Adults were exposed to Deltamethrin and DDT using WHO method. Cohorts of populations were further exposed to Pyperonil Butoxide (PBO) and Deltamethrin. Insecticide-exposed and unexposed co-horts were examined for metabolic enzyme activities. Results were compared between exposed and unexposed samples ANOVA (P<0.05). Results: Mosquitoes were identified as An. gambiae (89%, Ibadan; 0%, Badagry) and An. coluzzii (11%, Ibadan; 100%, Badagry). The populations showed varied level of resistance to Deltamethrin (26%, Ibadan; 71%, Badagry) and DDT (2%, Ibadan; 44%, Badagry). Mortality to Deltamethrin in-creased from 26% to 64% (Ibadan) and 71% to 84% (Badagry) when populations were pre-exposed to PBO. Biochemical analysis revealed significant high levels (P<0.05) of cytochrome P450 and GST in exposed samples. Conclusions: Cytochrome P450 and GST are involved in Deltamethrin and DDT resistance in Anopheles gambiae s.l populations in South-West Nigeria.

Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system, and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer among others. Recent data provide compelling evidence that distinct reactive astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (M^pro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as M^pro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

In this article, the new Hermite–Hadamard type inequalities are studied via generalized s-convexity on fractal sets. These inequalities derived on fractal sets are shown to be the generalized s-convexity on fractal sets. We proved that the absolute values of the first and second derivatives for the new inequalities are the generalization of s-convexity on fractal sets.

In this article, the new Hermite–Hadamard type inequalities are studied via generalized s-convexity on fractal sets. These inequalities derived on fractal sets are shown to be the generalized s-convexity on fractal sets. We proved that the absolute values of the first and second derivatives for the new inequalities are the generalization of s-convexity on fractal sets.

The effects of acidic electrolyzed water (AEW) on the microbiological and physicochemical properties of fresh-cut red cabbages were studied. The fresh-cut red cabbages and artificially inoculated red cabbages with Salmonella Typhimurium DT104 were washed with distilled water (DW) and different available chlorine concentration (ACC) of AEW for different times. AEW treatments significantly reduced the populations of native aerobic bacteria, molds and yeasts, and artificially inoculated S. Typhimurium DT104 compared to the DW treated and untreated red cabbage samples. The effectiveness of AEW treatments was greatly enhanced with increasing ACC and treatment times. S. Typhimurium DT104 were not detected in the washing water after the red cabbages treated by AEW. The surface color, pH, and total phenolic contents were did not significantly change when the red cabbages were washed with DW and 100 ppm AEW for 3 min. The anthocyanin contents and antioxidant activities of red cabbage were significantly reduced by 18.5% for cyanidin, 22.1% for pelargonidin, and 11.2% for DPPH radical scavenging activity, the impacts on the nutritional benefits of red cabbage were considered as limited and acceptable. The optimal process condition of AEW for washing red cabbage was 100 ppm for 3 min. In these conditions, most of the native microflora were inactivated, and artificial inoculated S. Typhimurium DT104 on the red cabbage were reduced by 40.2% (3.67 log CFU/g) and with minimal losses of nutrients and antioxidant activity, as well as no requirement of discontinuation treatment on the washing water.

MEMS (Micro-electromechanical Systems) becomes important increasingly due to the smarter and smaller fuze used in OICW (Objective Individual Combat Weapon). MEMS Safety and Arming (S&A) device is employed in different platforms and regions for small caliber projectile. Therefore, it is necessary to make a parametric study of the MEMS S&A device in different apply environments and explore the main sensitive factors of the MEMS S&A device to provide reference for designs. In this paper, based on the MEMS S&A device designed by our term, theory and finite element models are established, and the centrifugal insurance mechanism of the MEMS S&A device is parametric studied under the different speeds, temperature and thickness of the model by nonlinear dynamic method. By comparing the experimental and predicted results, the established FEM model is verified, and the conclusion is that the temperature and the centrifugal force are the main sensitive factors in the centrifugal insurance mechanism. In summary, we can suggest that the application environment, which the MEMS S&A device is suitable for, is the temperature equal to or slightly greater than normal temperature and the rotating speed higher than35000r/min of small caliber projectile.

Several plant species produce mixtures of odorous and volatile compounds known as essential oils (EOs). These mixtures play important roles in nature and have been utilized by man for pharmaceutical and agrochemical purposes. There are more than 3000 EOs reported in the literature with approximately 300 having commercial use, including the oils from Eucalyptus species. Such oils are rich in monoterpenes and have found applications as pharmaceuticals, agrochemicals, food flavorants and in the perfume industry. Such applications are related to their diverse biological and organoleptic properties. In view of their importance, we review in this article up to date information concerning chemical composition and biological activities of essential oils from different species of Eucalyptus. Among the 900 species and subspecies of the Eucalyptus genus¸ we examined 68 species. The studies associated with these species were conducted in 27 countries. We have focused on the antimicrobial, acaricide, insecticide and herbicide activities, hoping that such information will contribute in the advances of the research in this field. It is also intended that the information herein described can be useful in the rationalization of the use of Eucalyptus EOs as components for new pharmaceutical and agrochemical applications as well as food preservatives and flavorants.

This paper reports an experimental investigation on compression after low-velocity impact response for two lay-up configurations of symmetric CFRP laminated composite specimens obtained by reversing their angle-ply orientation, namely [0/-45/45/90]s versus [90/45/-45/0]s, the impact velocity of the projectile up to the BVID level being subsequently considered. To this aim, a modified Compression-After-Impact (CAI) test device is proposed that involves clamping the specimen's upper and lower edges between two adjustable wide and flat anti-buckling plates through a removable bolt-nut assembly. Such a solution relies on the fact that the specimen's active length is shortened, reducing the risk of global buckling. Besides, the bolts carry part of the load with minor localized bearing damage, provided that the metallic plates act as washers by supporting the bolt-bearing region laterally, thus avoiding crashing failures at the specimens’ loaded edges. With these settings, roughly the same percent decrease in the average values of maximum compression load (i.e., 22%) was recorded for both lay-up configurations impacted up to their BVID threshold, whereas in terms of compressive stiffness behavior, a reduction of 17 % was found for [0/-45/45/90]s specimens compared to 6 % obtained for [90/45/-45/0]s specimens.

The clinical features of increasing muscle weakening are shared by a diverse set of illnesses known as muscular dystrophies. In early childhood, males with Duchenne muscular dystrophy (DMD) exhibit proximal muscle weakening and calf enlargement, making it the most frequent X-linked disease of muscular dystrophy in children. Development of motor skills is typically delayed, and wheelchair confinement eventually leads to early death from heart or lung problems. In terms of function, ambulation, quality of life, and life expectancy, treatment approaches like corticosteroid therapy and intermittent positive pressure breathing have improved. This is a case report of a 6-year-old kid who had early ambulatory stage Duchenne Muscular Dystrophy and complained to the neuro-physiotherapy department about frequent falls, walking difficulties, and dyspnea when walking. Other grievances included being unable to get off the ground and having trouble ascending stairs. He had physiotherapy and dynamic neuromuscular stabilization for his complaints. The main goals of treatment were educating the family, respiratory training, preventing ankle plantar flexors, maintaining strength, balance and gait training.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

Polymer electrolyte was used as a medium for testing the performance of microband electrodes under conditions of linear diffusion. Cyclic voltammetry and chronoamperometry experiments were performed in such viscous medium, where diffusion rates are much slower than in fluid solutions. Confirmation of the existence of such conditions from the log i vs. log v or log i vs. log t relationships in the current equation always yielded values lower than the expected value of 0.5. This could indicate impure linear diffusion profile, i. e. some contribution from radial diffusion (edge effect). However, performing these tests in monomeric solvents of similar viscosities, such as glycerol or propylene glycol, gave the desired value of 0.5. These results lead to the conclusion that current equations which are based on Fick’s laws may not be applicable for polymer electrolytes, where various obstruction to diffusion make it a more complicated process than in monomeric solvents.

Cholinesterase (ChE) and secretase (BACE) inhibitors, and fibril- and β-amyloid-suppressing medicines are used to treat Alzheimer's disease (AD) symptomatically. The prevalence and complex nature of AD have increased the urgent need for multi-targeted directed ligands (MTDLs). This is because MTDLs can prevent potential drug-drug interactions during poly-therapy and have a better therapeutic profile than single targeted agents. Using piperazine linker or spacer and two primary scaffolds, benzofuran and 8-hydroxyquinoline, a unique class of multi-targeted medicines was recently reported by our group. These compounds showed re-markable effectiveness in inhibiting Aβ1-42 aggregation and acting as iron chelators.The results prompted us to synthesize an additional series of compounds as multimodal anti-AD agents and investigate its inhibitor activities to ChE (AChE/BChE) and BACE1 enzymes. The resulting in-hibitory effects suggested that the compounds under study might be used to improve cognitive function. The docking analysis' findings revealed that the compounds bind to AChE and BChE by forming H-bond interactions with amino acid residues at binding sites and µ-stacking inter-actions with aromatic residues, whereas the binding to BACE1 only revealed H-bond interac-tions with amino acid residues at binding sites.

Chronic Fatigue Syndrome (CFS) can be triggered by different factors and create a complex health situation. In the last decades incidence has been increasing. This situation is a clear example of how humans, viruses, and the environment are all connected. In the 90s cases related to CFS, com-plaints about a feeling of chronic fatigue, inability for everyday tasks, dull pain, cephalalgia, de-pression, anxiety, poor concentration. Clinical tests for EBV, HHV, CMV, IgG, IgM, T4 and T8 subsets were tested, along with hormones and hemogram tests. Most of the cases were women. The timeline of the medical history showed also myomas, breast lumps, premenstrual syndrome previously to CFS development. The nature of these conditions promoted the idea of a possible common link among them and CFS. Some cases also suffered from allergies, food intolerances, candidiasis, intestinal impairment, thyroid implications, endometriosis. As an initial working hypothesis, The Liver Link (TLL) was proposed in order to understand those different conditions affecting body, mind and emotional wellbeing. Considering liver implication can make a differ-ence in treatment and recovery. Low grade inflammatory conditions are related to Th2 predom-inance and liver functions. Functional disharmonies are very important because they usually still do not appear in any conventional tests. In 2002, TLL was presented as a framework to explain the concomitance of CFS and other conditions and the relationship with some viruses such as EBV, HHV, CMV, as a lecture in a congress at the University of Westminster (London). When SARS-CoV-2 outbroke, TLL helped to warn about the post-covid syndrome more likely to occur in specific individuals.

Caused by age or trauma, collapsed connective tissue can cause nerve entrapment and damage within the tarsal tunnel. Tarsal tunnel syndrome is relatively underdiagnosed. This study presents an intervention targeting damaged tissues surrounding the nerves and replacing the structural cushioning with a Wharton’s jelly tissue allograft. The eight selected patients from four clinical sites had tarsal tunnel-related defects. Patient outcomes were tracked on a 90-day calendar utilizing the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster University Arthritis Index (WOMAC). All patients had failed standard care practices for at least six weeks. Each patient received a Wharton’s jelly tissue allograft to sites around the affected tarsal tunnel. No patients experienced adverse reactions. Percent change calculated from the initial application to the 90-day follow-up showed an improvement of 59.43% in NPRS and a 37.58% improvement in WOMAC. This study provides evidence that WJ allograft applications are safe, minimally invasive, and efficacious for patients who have failed standard care treatments for tissue defects associated with Tarsal Tunnel syndrome. Limitations include the small cohort size and nonblinded nature. The results of this study warrant further research to confirm the efficacy, optimal dose, protocol, and durability of Wharton's jelly.

In our investigation of the time evolution of energy states Einstein’s interpretation from more than a century ago is found to have greater internal consistency than that of non-relativistic quantum mechanics. We choose to align more closely with his methods by abandoning the non-relativistic Hamiltonian method, which has been the standard for nearly a century, in favor of a relativistically correct Lagrangian method. Integral equations of motion for the absorption and emission of radiation are derived that underlie and anticipate the differentially motivated Schrödinger equation. This new interpretation applies to a large volume of experimental evidence of both classical and quantum mechanical origin. Among the examples discussed in support are Planck’s law describing black body radiation, matrix mechanics, the function of the simplest quantum mechanical system an electron cyclotron, chaos theory, and evolutionary biology.

This article deals with a finite-source stock-dependent stochastic inventory system with heterogeneous servers and retrial facility. The system can store up to S number of items, and the lifetime of each item follows an exponential distribution. The primary customers arrive in a finite waiting hall from a finite source and get service from the multi-channel (c-heterogeneous servers). The customer’s arrival rate depends on the present stock level. Those customers who arrive while the waiting hall is full enter into the finite orbit. Also, customers in the waiting hall can become impatient and enter the orbit. The (s,Q) ordering policy is adopted for the replenishment of stocks. In the steady state, the joint probability distribution of a number of items in the inventory, busy servers, customers in the waiting hall, and orbit is computed. The comparative numerical analysis of heterogeneous and homogeneous servers on the expected total cost, the average number of customers in the waiting hall and orbit, the fraction of successful retrial rate, and the average impatient customer rate are also carried out.

Contrary to pig farming in developed western countries, in a large part of the world, pigs are still traditionally kept, in small backyard farms, usually for family needs. Their main characteristics are low biosecurity, swill feeding, natural breeding and uncontrolled trade. Given the high number of backyard farms in Serbia and the risk they are thought to pose to intensive pig farming, the main aim of this study was to evaluate the prevalence of major viral diseases of swine among traditionally kept pigs in small holdings with low biosecurity. For this investigation, 222 serum samples from 69 backyard holdings were randomly selected and tested for PRRS, Aujeszky`s disease, PPV infection and Swine influenza by ELISA. The herd-level seroprevalence of PRRS, Aujeszky`s disease and PPV infection was 2.9%, 27.5% and 37.7%, respectively. Swine influenza seroconversion was not confirmed in any of the tested holdings. Despite widely distributed PPV and AD in backyard farms in Serbia, almost 50% of them are still negative for the all-tested disease. The backyard farms must be monitored, and owners educated as their role in eradication programs and obtaining country-free status may be crucial.

In this paper, we report orthogonal fuzzy versions of some celebrated iterative mappings. We provide various concrete conditions on the real valued functions J,S:(0,1]→(−∞,∞) for the existence of fixed-points of (J,S)-fuzzy iterative mappings. We obtain many fixed point theorems in orthogonal fuzzy metric spaces. We apply (J,S)-fuzzy version of Banach fixed point theorem to show the existence and uniqueness of the solution. We support these results with several non-trivial examples and applications to Volterra-type integral equations and fractional differential equations.

Biological pretreatment of lignocellulosic residues has the potential to serve as a sustainable, less energy-intensive alternative to harsh chemical treatments for enhancing cellulose accessibility, despite the requirement of a lengthy incubation period. The study characterized the simultaneous delignification of corn stover by the white-rot fungus Pyrenophora phaeocomes S-1, as well as the co-production of a ligno-hemicellulolytic enzyme cocktail consisting of laccase, xylanase, and mannanase. The maximum yields of all three components of the cocktail were achieved after just 4 days of incubation under solid-state conditions. Following a 40-day fermentation period, we achieved a cellulose recovery of 44.25 ± 1.72%, attributed to the activities of 133.88 U/gds of laccase, 14.93 U/gds of xylanase, and 1.34 U/gds of mannanase co-produced by the fungus in the medium. Subsequently, through the extraction of biologically treated biomass with 0.5N NaOH after 40 days, the cellulose recovery increased to 66.4 ± 1.39%. Enzymatic hydrolysis of the same, employing only 5 FPU/gds of in-house produced cellulases, resulted in the liberation of 397.84 mg/gds of total reducing sugars after 144h. The findings of this study encourage further optimization of biological pretreatment of lignocellulosic residues and enzymatic hydrolysis to enhance the yields of total reducing sugars for their valorization.

Hsp70.1 has dual functions as chaperone protein and lysosomal stabilizer. Previously, we reported that calpain-mediated cleavage of carbonylated Hsp70.1 causes ischemic neuronal death by inducing lysosomal rupture. Recently, we found that the consecutive injections of vegetable oil-peroxidation product ‘hydroxynonenal’ induces hepatocyte death via the similar cascade. As Hsp70.1 is related also to fatty acid β-oxidation in the liver, its deficiency is known to cause accumulation of fat. Genetic deletion of betaine-homocysteine S-methyltransferase (BHMT) was reported to perturb choline metabolism, inducing decrease of phosphatidylcholine with the resultant hepatic steatosis. Here, focusing on disorders of Hsp70.1 and BHMT, we studied the mechanism of hepatocyte degeneration and steatosis, using monkeys after the consecutive injections of synthetic hydroxynonenal. As these monkeys showed a significant impairment of liver functions, the liver tissues without and with hydroxynonenal injections were compared by proteomics, immunoblotting, immunohisto-chemical and electron microscopic analyses. Western blotting showed upregulation of neither Hsp70.1 nor BHMT, but an increased cleavage of both proteins. Proteomics showed downregulation of Hsp70.1, while 2-fold increments of carbonylated BHMT. Hsp70.1 carbonylation was negligible, showing a marked contrast to ischemic neurons which were associated with ~10-fold increments. The control liver histologically showed lipid droplets in Ito cells, but lipid depositions within hepatocytes were very little. In contrast, after hydroxynonenal injections, widespread fatty degeneration and focal coagulation necrosis were observed with accumulation of numerous tiny lipid droplets within and around the degenerating/dying hepatocytes. Electron microscopy showed lysosomal membrane permeabilization/rupture, remarkable dissolution of mitochondria and rough ER membrane, and proliferation of abnormal peroxisomes. It is probable that disruptions of rough ER caused impaired synthesis of Hsp70.1 and BHMT proteins, while impairments of mitochondria and peroxisomes presumably contributed to the sustained generation of reactive oxygen species. Since both Hsp70.1 and BHMT are vulnerable to the long-standing oxidative stressor, hydroxynonenal-induced disorders facilitated degeneration and steatosis of hepatocytes, respectively.

Antimicrobial resistance is on the rise, and there aren't enough new treatments to combat it. This might send the modern world back to the pre-antibiotic age. The molecular hybrids of pyrazolo[3,4-b]pyridine and triazole have been designed, synthesized, and analyzed for their drug-like molecule nature and in vitro analyses for their inhibition potentials against S. Aureus and K. Pneumoniae. The compounds CY-R2-25 and CY-R2-28 have been identified as the high potential molecules in this series based on in vitro experiments. CY-R2-25 has zone of inhibition values of 15 0.82 and 14 0.7, whilst CY-R2-28 has the zone of inhibition values of 18 0.95 and 16 0.82 against S. Aureus and K. Pneumoniae, respectively. MIC and MIB values for CY-R2-25 and CY-R2-28 against S. Aureus and K. Pneumoniae are 0.25 and 0.5, respectively.

Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the non-resistant but otherwise identical 20A>T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to Northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here we address this finding with the replacement hypothesis, according to which pre-existing genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, a gradual evolutionary process under selection can hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A>G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called Interaction-based Evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directional mutational responses to specific environmental pressures are possible. Such responses need to be further tested by future studies in natural and artificial settings.

Ethylene is a plant hormone controlling physiological and developmental processes such fruit maturation, hairy root formation and leaf abscission. Its effect on regeneration systems, such as organogenesis and somatic embryogenesis (SE), has been studied and progresses in molecular biology techniques have contributed to unveil mechanisms behind its effects. This compound affects regeneration differently, depending on the species, genotype and explant. In some species, ethylene seems to revert recalcitrance in genotypes with low regeneration capacity. However, its effect is not addictive, since in genotypes with high regeneration capacity this ability decreases in the presence of ethylene precursors, suggesting that regeneration is modulated by ethylene. Several lines of evidence have shown that the role of ethylene on regeneration is markedly connected to biotic and abiotic stresses as well as to hormonal-crosstalk, in particular with key regeneration hormones and growth regulators of the auxin and cytokinin families. Transcriptional factors of the ethylene response factor (ERF) family are regulated by ethylene and strongly connected to SE induction. Thus, an evident connection between ethylene, stress responses and regeneration capacity is markedly established. In this review the effect of ethylene and the way it interacts with other players during organogenesis and somatic embryogenesis is discussed.

Water deficit caused by drought is a significant threat to crop growth and production. Nitric oxide (NO), a water- and lipid-soluble free radical, plays an important role in cytoprotection. Apart from a few studies supporting the role of NO in drought responses, little is known about this pivotal molecular amendment in the regulation of abiotic stress signaling. In this review, we highlight the knowledge gaps in NO roles under drought stress and the technical challenges underlying NO detection and measurements, and we provide recommendations regarding potential avenues for future investigation. The modulation of NO production to alleviate abiotic stress disturbances in higher plants highlights the potential of genetic manipulation to influence NO metabolism as a tool with which plant fitness can be improved under adverse growth conditions.

Nitric oxide (NO) is involved in physiological processes, including vasodilatation, wound healing and antibacterial activities. As NO is a free radical, designing drugs to generate therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL) - chitosan (CS) hydrogel, with an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL^-1 of hydrogel, which corresponds to 1 mmol·L^-1 of GSNO). Interestingly, the concentration range in which the NO-releasing hydrogel demonstrated an antibacterial effect was not found to be toxic to the Vero mammalian cell. Thus, the GSNO-PL/CS hydrogel is a suitable biomaterial for topical NO delivery applications.

Yeast, crucial in beer production, holds promise as a valuable by-product resource, known as brewer's spent yeast (BSY), with potentially beneficial physiological effects. This study aimed to compare the composition and soluble polysaccharide content of Brewer's spent yeast with those of pure cultured yeast strains, namely Saccharomyces cerevisiae (SC) and S. boulardii (SB), to facilitate the utilization of BSY as an alternative source of functional polysaccharides. BSY exhibited significantly higher carbohydrate content and lower crude protein content than SC and SB cells. The residues recovered through autolysis were 53.11%, 43.83%, and 44.99% for BSY, SC, and SB, respectively. Notably, the polysaccharide content of BSY residue (641.90 μg/mg) was higher than that of SC (553.52 μg/mg) and SB (591.56 μg/mg). The yields of alkali-extracted water-soluble polysaccharides were 40%, 30%, and 35% for BSY, SC, and SB, respectively, with BSY comprising a higher proportion of water-soluble saccharides than SC and SB, including 49.3% mannan and 20.1% β-glucan. Furthermore, BSY demonstrated antioxidant activities, including superoxide dismutase (SOD), ABTS, and DPPH scavenging potential, suggesting its ability to mitigate oxidative stress. BSY also exhibited a significantly higher total phenolic compound content, indicating its potential as an effective functional food material.

The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-like family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which reveal significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF's interactions with GATA4, MEF2C, NKX2.5 and other ~ 90 potential genes that participate in the regulation of the hypertrophic environment (or CVD's Environment). Also, the GO analysis showed genes containing the motif CACCC were enriched for multiple CVD’s, in combination with STRING analysis these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

I demonstrate that Bell's theorem is based on circular reasoning and thus a fundamentally flawed argument. It unjustifiably assumes the additivity of expectation values for dispersion-free states of contextual hidden variable theories for non-commuting observables involved in Bell-test experiments, which is tautologous to assuming the bounds of ±2 on the Bell-CHSH sum of expectation values. Its premises thus assume in a different guise the bounds of ±2 it sets out to prove. Once this oversight is ameliorated from Bell's argument by identifying the impediment that leads to it and local realism is implemented correctly, the bounds on the Bell-CHSH sum of expectation values work out to be ±2√2 instead of ±2, thereby mitigating the conclusion of Bell's theorem. Consequently, what is ruled out by any of the Bell-test experiments is not local realism but the linear additivity of expectation values, which does not hold for non-commuting observables in any hidden variable theories to begin with.

Diabetic retinopathy (DR), a major complication of prolonged diabetes, poses a significant risk of vision loss. Early detection is critical for effective treatment, yet traditional diagnostic methods by ophthalmologists are time-consuming, costly, and subject to variability. This study introduces a novel approach employing a hybrid Convolutional Neural Network-Radial Basis Function (CNN-RBF) classifier integrated with Multi-Scale Discriminative Robust Local Binary Pattern (MS-DRLBP) features for enhanced DR detection. We implemented advanced image preprocessing techniques, including noise reduction, morphological operations, and Otsu’s thresholding, to optimize blood vessel segmentation from retinal images. Our method demonstrates exceptional performance in screening DR, achieving an average of 96.10% precision, 95.35% sensitivity, 97.06% specificity, and 96.10% accuracy. These results significantly outperform traditional methods and offer a promising tool for remote and efficient screening of DR. Applied to publicly available datasets, this research contributes to the development of accessible, accurate diagnostic methods in ophthalmology, potentially reducing the global burden of diabetic vision loss.

Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as medical procedure for skin neoplasms’ treatment, especially for Classic Kaposi’s Sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and local control of CKS disease. Primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions’ treatment. Nineteen CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt, meanwhile 3 and 4 out of 19 patients obtained a Partial response (PR), so that they underwent to a second and a third ECT treatment, each other. Clinical response was evaluated during all the time of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. CKS skin lesions control still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors’ recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi’s Sarcoma locally advanced lesions.

Parkinson’s Disease (PD) is a debilitating neurodegenerative disease, causing loss of motor function, and in some instances, cognitive decline and dementia, in those affected. The quality of life can be improved, and disease progression delayed through early interventions, however, current methods of confirming a PD diagnosis are extremely invasive. This prevents their use as a screening tool for the early onset stages of PD. We propose a surface imprinted polymer (SIP) electroimpedance spectroscopy (EIS) biosensor for detecting α-Synuclein (αSyn) and its aggregates, a biomarker that appears in saliva and blood during the early stages of PD as the blood brain barrier degrades. The surface imprinted polymer stamp is fabricated by low temperature melt stamping polycaprolactone (PCL) on interdigitated EIS electrodes. The result is a low-cost, small footprint biosensor that is highly suitable for non-invasive monitoring of the disease biomarker. The sensors were tested with αSyn dilutions in deionized water, and in constant ionic concentration matrix solutions with decreasing concentrations of αSyn to remove the background effects of concentration. The device response confirmed the specificity of these devices to the target protein of monomeric αSyn. The sensor limit of detection was measured to be 5 pg/L and its linear detection range was 5 pg/L – 5 µg/L. This covers the physiological range of αSyn in saliva and makes this a highly promising method of quantifying αSyn monomers for PD patients in the future. The SIP surface was regenerated, and the sensor reused to demonstrate its capability for repeat sensing as a potential continuous monitoring tool for the disease biomarker.

Inflammatory bowel diseases, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody blocking the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of ‘real-world’ data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists have been reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, have been reported. This review explores results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.

Purpose – The paper aims to view how researchers have operationalized social impact assessment for construction projects over the last ten years. Design/methodology/approach – A systematic review was used to investigate case studies in the Social Life-Cycle Assessment (S-LCA) to analyze the application of the methodology. A qualitative study of 19 articles published between 2012 and 2022 was used to collect content on multiple categories impeding S-LCA through case studies in the construction industry. Findings – Our results showed the existence of limitations on the qualitative and quantitative aspects in measuring the social indicators. They were associated with the scoring method and the lack of data in some articles. Social implications – From this review, we understood that S-LCA has flaws in terms of the quality of the measurement, scoring method, and the lack of social data. Lack of social data means social impacts are being neglected and not assessed properly since there are several challenges pointed out throughout literature Originality/value – The originality of this research is that it focuses on case studies in the construction industry. It studies the operationalization of the S-LCA in this specific industry showing the different characteristics and challenges in the last 10 years.

This paper discusses a passive control issue for Nonlinear Time-Varying (NTV) systems subject to stability and attenuation performance. Based on the modeling approaches of Takagi-Sugeno (T-S) fuzzy model and the Linear Parameter-Varying (LPV) model, a Parameter-Dependent Polynomial Fuzzy (PDPF) model is constructed to represent the NTV systems. According to Parallel Distributed Compensation (PDC) concept, a parameter-dependent polynomial fuzzy controller is built to achieve robust stability and passivity of PDPF model. Furthermore, the passive theory is applied to achieve the performance constraining the disturbance effect on the PDPF systems. To develop the stability criteria, by introducing a parameter-dependent polynomial Lyapunov function, one can derive some stability conditions which belong to the term of Sum-Of-Squares (SOS) form. Based on the Lyapunov function, two stability criteria are proposed to design the corresponding PDPF controller such that the NTV system is robustly stable and passive. Finally, a numerical example is applied to demonstrate the effectiveness of the proposed stability criterion.

Image encryption is increasingly becoming an important area of research in information security and network communications, as digital images are widely used in various applications and are vulnerable to various types of attacks. In this research work, a color image cryptosystem that is based on a 3-layer permutation-substitution network (PSN) is proposed. For every layer, an encryption key and an S-box are generated and utilized. Those are based on a four-dimensional (4D) dynamical Chen system of a fractional-order, the Mersenne Twister, OpenSLL, Rule 30 Cellular Automata and Intel’s MKL. The sequential application of Shannon’s ideas of diffusion and confusion for 3 times guarantees a total distortion of any input plain image, resulting in a totally encrypted one. Apart from the excellent and comparable performance to counterpart algorithms from the literature, showcasing resistance to visual, statistical, entropy, differential, known plaintext and brute-force attacks, the proposed image cryptosystem provides an exceptionally superior performance in 2 aspects: a vast key space of 2^1658 and an average encryption rate of 3.34 Mbps. Furthermore, the proposed image cryptosystem is shown to successfully pass all the tests of the NIST SP 800 suite.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed in late stages, when tumor has disseminated to other organs. Besides, it is common to observe that malignant cells acquire tumor escape mechanisms which leads to therapy resistance. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) which exhibited selective cytotoxicity against SW480, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated a little deeper in the possible mechanism of these molecules to identify potential therapeutic alternatives for the treatment of CRC. Both compounds induced cell damage and reduced ROS formation. Further evaluations showed that SAC-CAFA-MET induces cell death independent from caspases and p53, but probably mediated by the negative regulation of the proapoptotic Bcl-2. In addition, the lack of activation of caspase 8 and the positive regulation of caspase 3 induced by SAC-CAFA-PENT suggest this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathway. Besides, the down regulation of IL-6 by SAC-CAFA-PENT suggests it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which hybrids elicits apoptosis in human colorectal adenocarcinoma SW480. Meanwhile, DFT calculations suggest that hybrids would produce effects in modulation of ROS in SW480 cells via hydrogen atom transfer pathway (HAT). Finally, both, SAC-CAFA-MET and SAC-CAFA-PENT displayed a favorable pharmacokinetic profile. The current work highlights the potential of the lead compounds SAC-CAFA-MET and SAC-CAFA-PENT as potential agents for colorectal cancer chemoprevention.

We investigate the effect of geopolitical risk on the returns of the Information Technology, Communication Services, and Consumer Staples sector firms within the S&P 500 index. We use the event study methodology and perform more than 17,000 regressions to provide empirical evidence at the sector level that geopolitical risk leads to different responses across these 3 sectors. The response of the Information Technology sector is negative for all event windows under study, except the one spanning 10 days prior to the geopolitical event and 10 days after. The Communication Services sector has positive returns as a result of geopolitical events for all event windows, except the one from the geopolitical event date and 5 days after. The Consumer Staples sector shows a negative impact on geopolitical risk for all event windows except the one from the geopolitical event date and 5 days after, demonstrating a negative correlation to the Communication Services sector.

The cyclic load applied to civil and mining structures can lead to a reduction of the materials’ strength, different from that which would occur with a monotonous load. Numerous cases can be found where the decay of the rock parameters subjected to this type of stress leads to progressive or sudden collapse: among them, tunnel walls, pillars and slabs in mining operations, roads with a heavy vehicle transit, abutments of bridges and dams can be quoted. The topic can therefore be fundamental for a correct structural design, to avoid problems during the life of the structure. However, given the heterogeneity of the rock materials and the difficulty of their characterization under this aspect, an unequivocal analysis is hardly achievable. Then, the discussion initially develops through a general historical review of the concept of fatigue, with a synthetic collection of case histories. The laboratory tests on rock samples are then examined and the most important results obtained are discussed. Finally, a comparison between different types of tests is proposed. The experimental data are expressed through the Wӧhler diagram. The goal is to fill the lack of design codes or standards in the field of cyclic stresses applied to rock materials, the understanding of its effect being of great interest in order to apply suitable parameters in the design phase.

The astacin protease Meprin β represents an emerging target for drug development due to its potential involvement in disorders such as acute and chronic kidney injury and fibrosis. Here, we elaborate on the structural basis of inhibition by a specific Meprin β inhibitor. Our analysis of the crystal structure suggests different binding modes of the inhibitor to the active site. This flexibility is caused, at least in part, by movement of the C-terminal region of the protease domain (CTD). The CTD movement narrows the active site cleft upon inhibitor binding. Compared with other astacin proteases, among those the highly homologous isoenzyme Meprin α, differences in the subsites account for the unique selectivity of the inhibitor. Although the inhibitor shows substantial flexibility in the orientation within the active site, the structural data as well as binding analyses including molecular dynamics simulations support a contribution of electrostatic interactions, presumably by arginine residues, to binding and specificity. Collectively, the results presented here and previously support an induced fit and substantial movement of the CTD upon ligand binding and, possibly, during catalysis. To the best of our knowledge, we here present the first structure of a Meprin β holoenzyme containing a zinc ion and a specific inhibitor bound to the active site. The structural data will guide rational drug design and the discovery of highly potent Meprin inhibitors.

In this paper, a multi-mode waveguide-based optical resonator is proposed for an integrated optical refractive index sensor. Conventional optical resonators have been studied for single-mode waveguide-based resonators to enhance the performance, but mass production is limited owing to the high fabrication costs of nano-scale structures. To overcome this problem, we designed an S-bend resonator based on a micro-scale multi-mode waveguide. In general, multi-mode waveguides cannot be utilized as optical resonators, because of a performance degradation resulting from modal dispersion and an output transmission with multi-peaks. Therefore, we exploited the mode discrimination phenomenon using the bending loss, and the resulting S-bend resonator yielded an output transmission without multi-peaks. This phenomenon is utilized to remove higher-order modes efficiently using the difference in the effective refractive index between the higher-order and fundamental modes. As a result, the resonator achieved a Q-factor and sensitivity of 2.3x10³ and 52 nm/RIU, respectively, using the variational finite-difference time-domain method. These results show that the multi-mode waveguide-based S-bend resonator with a wide line width can be utilized as a refractive index sensor.

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in Renovascular hypertension (RVH). The activation of the Renin-Angiotensin System (RAS) is crucial in the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n=5/group) were treated with boldine (50mg/kg/day, gavage) for 6 weeks after 2K1C surgery (pressure≥180mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. α-SMA and Col III were used as markers of kidney damage; ED-1 and Osteopontin (OPN) as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced UProt/UCrea ratio, plasma TBARS and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1 and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

Changing the symmetry of spin from SU(2) to the quaternion group, $Q_8$, has many ramifications. In this paper we first summarize the properties of Q-spin and then discuss some of those resulting changes.

(1) Background: Alzheimer’s disease (AD) presents a significant challenge in terms of discovering novel diagnostic methods and therapies. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate the mechanism of action of Apelin-13 in an in vivo model of AD induced by streptozocin (STZ); (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. The Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests. The main methods included behavioral assessment, histological analysis, and biochemical assays to evaluate synaptic plasticity and oxidative stress signaling pathways; (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated through the enhancement of synaptic plasticity and attenuation of oxidative stress signaling pathways; (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

This study aimed to investigate the relationship between sleep duration, dementia severity, age, and ANS regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease, hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity using the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, and medication (antipsychotics) as covariates. A sleep duration of 7–8 h per night was associated with better ANS regulation than other sleep durations, as indicated by sympathovagal balance (p = 0.005). ANS dysregulation was characterized by a 20.7% increase in sympathetic nervous system activity and a 14.8% decrease in parasympathetic nervous system (PSNS) activity. We found a significant correlation between dementia severity and PSNS activity (p = 0.04) and observed an inverted U-shaped association between sleep duration and ANS regulation. This pilot study demonstrated that a sleep duration of 7–8 h per night may be critical in maintaining optimal ANS regulation. Bidirectional associations between sleep duration, inadequate sleep duration, aging, and ANS regulation warrant further investigation.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

Sequential properties can violate Bell-type inequalities without direct influence on each other, but only if detected in pairs. This is demonstrated below with theoretical arguments, and with a straightforward toy model. Rotating arrows can have transient qualities that produce maximal Bell violations with predetermined values. Any non-signaling phenomenon (classical, or non-classical) can also be interpreted as local.

The removal of H2S from natural gas and other gases such as biogas, refinery gases, and coal gas is required because H2S is toxic and corrosive, even in traces. Zeolites are widely used in the removal of H2S from the above-mentioned gases. In this work, we prepared an Ag-exchanged 13X molecular sieve by using different concentrations of AgNO3 to increase its adsorption properties. XRD, SEM, and BET techniques were used to characterize samples. When compared to unmodified 13X, the adsorption capacity of AgII-13X increased by about 50 times. The results of this study suggest that the silver-modified 13X molecular sieve is highly effective at extracting H2S from natural gas.

Lizards in Bulgaria hibernate in winter. Yet, individuals of many species were found active in this period. Cases of winter activity of Podarcis muralis and P. erhardii in the country have been published, but this behavior has not been studied in detail. The purpose of this research was to observe and analyze the winter activity of these two species in the city of Blagoevgrad. The observations took place at two sites in days with high solar radiation in December, January, and February 2015–2017. One of the sites was a typical urban territory, inhabited only by P. muralis. The other site was a suburban area, inhabited by P. erhardii. The number of the active individuals of the Common Wall Lizard recorded was about 8.5 times higher than that of the Erhard's Wall Lizard. The lowest air temperature at which P. muralis was observed was -4°C and for P. erhardii it was +0.5°C. Individuals of both species were registered only at positive substrate temperatures. Representatives of all age groups of P. muralis were recorded often with dorsoventrally flattened bodies while basking. On the other hand, few juveniles of P. erhardii were found active and they flattened their bodies very rarely.

Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as substitutes for bisphenol A (BPA) in the plastic industry, driven by concerns over the adverse effects of BPA. However, there is a lack of infor-mation on the extent of exposure to these chemicals in children. This study aims to assess the extent of BPA, BPF, and BPS exposure and determine factors that influence such exposure. A group of Thai children (age 6-13 years, n=358) were recruited between October 2019-2020. Two first morning void was collected one week apart. Demographic and exposure-related information was gathered. Urinary concentrations of bisphenols were analyzed by liquid-chromatography and tandem mass spectrometry. Correlation between bisphenol concentrations and various factors was determined using generalized estimating equations with linear model. BPA, BPF, and BPS were detected at 79.6%, 31.0%, and 16.8%, with geometric mean (GM) concentrations of 1.41, 0.013, and 0.014 ng/mL respectively. Younger children aged < 10 years exhibited 1.3-1.6 times higher GM levels of all bisphenols compared to older children. Exposure to food stored in plas-tic containers were associated with higher levels of BPF and BPS. In conclusion, BPA was the most fre-quently detected bisphenol in urine samples from Thai children, followed by BPF and BPS.

The complexity of objects and control systems increases the requirements for mathematical models. The structural identifiability (SI) assessment of nonlinear systems is one of the identification problems. Until now, this problem solves by parametric methods using various approximation methods. This approach is not always effective under uncertainty. We apply an approach to SI estimation based on the analysis of virtual structures. The requirements form for the system input based on the expansion of the excitation constancy property and S-synchronizability. The approach generalization to structural identifiability used in the analysis of systems with symmetric nonlinearity is given. homothety and identifiability conditions for systems with non-symmetric nonlinearities (SNN) obtained. The detectability and recoverability proofed for virtual frameworks (VF) guaranteed the SI estimation under uncertainty. The conditions under which the non-symmetric nonlinearity is hypothetical symmetric nonlinearity obtained. SI estimation examples considered for closed nonlinear systems under uncertainty.