The purpose of this paper is to review the involvement of mitochondria in the actions of nitroglycerin (glycerol trinitrate -GTN) and the redox disturbances underlying diseases it treats. The paper begins by explaining complex I as the initial site of formation of superoxide and the process whereby it leads to the development of glutathione dependent tolerance. Next, the paper describes new formulations for preventing tolerance. The paper ends by illustrating diseases that may benefit from treatment with novel glutathione based GTN formulations and treatment approaches.

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.

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.

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.

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.

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.

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.

The dispersive and polar properties of materials, and especially of polymers and copolymers play an important role in several engineering applications implying their surfaces and interfaces. The surface energetic properties of poly(styrene-co-butadiene) have never been studied. We proposed in this study an accurate determination of such properties by using the inverse gas chromatography (IGC) at infinite dilution. Background: The IGC surface technique led to the dispersive and polar properties of poly(styrene-co-butadiene) rubber (SBR) by adsorption of organic solvents at various temperatures. Methods: Our new methodology based on the thermal Hamieh model and the London dispersion interaction energy was used to determine the London dispersion surface energy, the polar acid-base surface energy, and the Lewis acid-base properties of the copolymer. Results: The different surface energy parameters of the SBR were obtained as a function of temperature from the chromatographic measurements. Conclusions: The dispersive and polar free energies of adsorption of the various n-alkanes and polar molecules on poly(styrene-co-butadiene) were determined at different temperatures. A decrease of the London dispersive surface energy and the polar Lewis acid-base surface energies of SBR was highlighted when the temperature increased. It was showed a Lewis amphoteric character of poly(styrene-co-butadiene) with a highest basic constant 10 times larger than its acidic constant.

This paper aims to outline the effectiveness of modern universal gate quantum computers when utilizing different configurations to solve the B-SAT(Boolean Satisfiability) problem. The quantum computing experiments are performed using Grover’s Search algorithm to find a valid solution. The experiments are performed under different variations to demonstrate their effects on the results. Changing the number of shots, qubit mapping, and using a different quantum processor are all among the experimental variables. The study also branches into a dedicated experiment highlighting a peculiar behavior that IBM quantum processors exhibit when running circuits with a certain number of shots.

The Ro60 autoantigen is an RNA-binding protein, and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates quality control and cellular dis-tribution of YRNAs, retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal TLRs and cytoplasmic RNA sensors, which typically sense patho-gen-associated molecular patterns (PAMPs) and mount the first line of defence against invading pathogens. However, recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases including Sjögren's disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for an-ti-drug antibody response among rheumatic patients. Understanding Ro60’s structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mecha-nisms of autoimmune conditions.

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.

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.

To protect skin from harmful ultraviolet (UV), zinc oxide (ZnO) with tannin from gallnuts was treated on cotton and polyester fabrics in this study. Before the treatments, the fabrics were dyed with shikonin and xanthophyll from Gromwell and Cape Jasmine. First, this study found that xanthophyll was more effective at preventing light fade or discoloration than shikonin. Despite the highest K/S, the untreated cotton in violet faded the most intensely when exposed to UV. The color variation of untreated polyester was narrow, with little change in L, a*, and K/S. Due to the non-photochemical xanthophyll, the yellow-dyed samples treated with ZnO/polyphenol did not vary yellowness (b*: 28.838) significantly, while the violet fabrics displayed a significant decrease in K/S and an increase in b*. The combination of ZnO and polyphenol treatment improved UV absorption at 350 to 250 nm. Cu-mordanting after ZnO/polyphenols treatment caused the violet cotton to turn reddish from blueish (negative to positive b*), with a hue change of 316° to 59° and the highest ΔE (25.90±4.34) after UV exposure. In this study, the combination of ZnO/polyphenol with Cu-mordants contributed the xanthophyll-dyed polyester to achieve a minimum ΔE and keep chroma and hue after UV exposure.

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.

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.

We report the case of a 45-year-old Caucasian man who was treated upfront with brentuximab vedotin (A) and doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) for advanced-stage classical Hodgkin's lymphoma (cHL). Right after completing the 6th cycle of induction therapy, he developed serotine fever, progressive clinical deterioration, symptomatic splenomegaly and se-vere anemia. Extensive infectious disease evaluations and serial PET scans were conducted to rule out lymphoma progression. Finally, a diagnosis of visceral leishmaniasis (VL) was performed. The patient was treated with parenteral amphotericin B, with rapid and complete resolution of clinical and laboratory abnormalities. We described this rare case of infectious complication after A+AVD delivered for cHL, and we performed a comprehensive review of the literature on the occurrence of VL in the context of non-HL and cHL, since this infection is becoming increasingly prevalent in non-tropical countries.

The immunization against Gonadotropin-Releasing Hormone (GnRH) has been successfully explored and developed for the parenteral inoculation of animals, aimed at controlling fertility, reducing male aggressiveness, and preventing boar taint. Although effective, these vaccines may cause adverse reactions at the injection site, including immunosuppression and inflammation, as well as involvement of laborious and time-consuming procedures. Oral vaccines represent an advancement in antigen delivery technology in the vaccine industry. In this study, a Salmonella enterica serovar Typhimurium (S. Typhimurium) mutant lacking the pathogenicity island 2 (S. Typhimurium ΔSPI2) was used as a vehicle and mucosal adjuvant to deliver two genetic con-structs, in an attempt to develop an oral immunological preparation against Gonadotropin hormone-releasing hormone (GnRH). S. Typhimurium ΔSPI2 was transformed to carry two plasmids containing a modified GnRH gene repeated in tandem (GnRXG/Q), one under eu-karyotic expression control (GnRX GQ_OptMamm_V3::GnRXG/Q) and another under prokar-yotic expression control (pJexpress::GnRXG/Q). Group of three male BALB/c mice were orally immunized and tvaccination boosted 30-days later. Oral administration of S. Typhimurium ΔSPI2transformed with both plasmids was effective in producing antibodies against GnRXG/Q, leading to a decrease in serum testosterone levels and testicular tissue atrophy, evidenced by a reduction in the transverse tubular diameter of the seminiferous tubules and a decrease in the number of layers of the seminiferous epithelium in the testes of the inoculated mice. These re-sults suggest that S. Typhimurium ΔSPI2can be used as a safe and simple system to produce an oral formulation against GnRH, and that Salmonella-mediated oral antigen delivery is a novel, yet effective, alternative to induce an immune response against GnRH in a murine model, war-ranting further research in other animal species.

This paper focuses on the long-standing issue of galactic rotation, i.e. the discrepancy between observed rotation rates and predictions based on Newtonian gravity. While Newton's law holds within the solar system, it fails to explain the higher-than-expected rotation speeds of galaxies, particularly at greater distances from their centers. This study finds that Newton's gravitational formula applies only when gravitational lensing has a negligible impact. We examine the gravitational force on objects farther from the galactic center, where the lensing effect of a supermassive black hole becomes significant. This lensing causes the actual gravitational force to exceed Newtonian predictions, with the discrepancy increasing with distance. This effect offers an alternative explanation for the galactic rotation curve without the need for dark matter. Our findings suggest that Newton's formula requires revision to account for gravitational lensing, a key factor in understanding galactic dynamics and its broader cosmic implications.

This study aims to explore methods for automating the replication of correlated portfolios across shares using various algorithms. The goal is to select one algorithm for implementation in a visualization tool that will facilitate portfolio building. The dynamics of the stock market provide a comprehensive view of the global economy, acting as a catalyst for stakeholders to participate and benefit various sectors financially, primarily through investments in companies that yield returns and contribute to the economy. The evaluation and comparison of these algorithms are crucial for making well-informed decisions regarding the core objectives of the study. Ultimately, a determination will be made as to whether the program can effectively analyse data from Yahoo finance to provide a quick overview of the financial market state of companies in the S&P 500 US stock prices.

Phosphorus (P) is an important and irreplaceable macronutrient. It is central to energy and information storage and exchange in living cell. P is an element with “broken geochemical cycle” since it lacks abundant volatile compounds capable of closing the P cycle. P fertilizers are critical for global food security, but the reserves of minable P are scarce and non-evenly distributed between countries of the world. Accordingly, the risks of global crisis due to limited access to P reserves is expected to be graver than those entailed by competition for fossil hydrocarbons. Paradoxically, despite the scarcity and value of P reserves, its usage is extremely inefficient: current waste rate reaches 80% giving rise to a plethora of unwanted consequences such as eutrophication leading to harmful algal blooms. Microalgal biotechnology comprise a promising solution to tackle this challenge. The proposed review briefly presents the relevant aspects of microalgal P metabolism such as cell P reserve composition and turnover, and the regulation of P uptake kinetics for maximization of P uptake efficiency with the focus on novel knowledge. Multifaceted role of polyPhosphates, the largest cell depot for P, is discussed with emphasis on the P toxicity mediated by short-chain polyPhosphates. Opportunities and hurdles of P bioremoval via P uptake from waste streams with microalgal cultures, either suspended or immobilized, is discussed along with the role of bacterial components of microalgal-bacterial consortia in these processes. Possible avenues of P-rich microalgal biomass such as biofertilizer production or extraction of valuable polyPhosphates and other bioproducts are considered. The review concludes with a comprehensive assessment of the current potential of microalgal biotechnology for ensuring the sustainable usage of phosphorus.

In recent years, marine natural products have become one of the most important resources of novel lead compounds for critical diseases associated with age. Spirulina, a dietary supplement made from blue-green algae (cyanobacteria: scientific name Arthrospira platensis), is particularly rich in phycocyanin, a phycobiliprotein, which accounts for up to 20% of this cyanobacterium’s dry weight and is considered responsible for its anti-cancer, anti-inflammatory and antioxidant activities. Although the anti-aging activity of phycocyanin has been investigated, how exactly this compound works against aging remains elusive. Aim of our research is to use the yeast Saccharomyces cerevisiae as a model organism to investigate the anti-aging properties of phycocyanin from A. platensis. Our results show that phycocyanin has a powerful anti-aging effect, greatly extending the chronological life span of yeast cells in a dose-dependent way, being the effect pronounced also when cells were grown in SD medium under calorie restriction conditions (0.2% glucose). Both ROS and accumulation of dead cells were followed by staining chronologically aged cells with dihydrorhodamine 123 (DHR123) and propidium iodide (PI). Interestingly, we found that most of the aged phycocyanin treated cells, which were unable to form colonies, were actually ROS+/PI–. Finally, we show that the moment in which phycocyanin is added to the culture does not substantially influence its effectiveness in counteracting chronological aging.

Machine learning approaches are currently used to understand or model complex physical systems. In general, a substantial number of samples must be collected to create a model with reliable results. However, collecting numerous data is often relatively time-consuming or expensive. Moreover, the problems of industrial interest tend to be more and more complex and depending on a high number of parameters. High dimensional problems intrinsically involve the need of large data amount through the curse of dimensionality. That is why, new approaches based on smart sampling techniques are investigated to minimize the number of samples to be given to train the model, such as Active Learning methods. Here, we propose a technique based on a combination of Fisher information matrix and of Sparse Proper Generalized Decomposition that enables the definition of a new Active Learning informativeness criterion in high dimensions. We provide examples proving the performances of this technique on a theoretical 5D polynomial function and on an industrial crash simulation application. The results prove that the proposed strategy over-perform the usual ones.

Keywords: Parkinson’s disease; sleep disorders; GBA; Parkin

Hypsizygus marmoreus has become one of the most popular edible mushrooms due to its high nu-tritional and economic value. Previous researchers found that Serratia odorifera could promote the growth of H. marmoreus by producing and secreting some of its inducers. However, the specific mechanism of action was still unclear. In this study, we found that exogenous addition of sterile fermentation filtrate (HZSO-1), quorum sensing (QS signaling molecules, 3-oxo-C6-HSL, cy-clo(Pro-Leu), and cyclo(Tyr-Leu) could significantly promote the growth of H. marmoreus, increase the number of clamp junctions, and the diameter of mycelium (P < 0.05). In addition, non-targeted metabolomic analysis has revealed that 706 metabolites were detected in the treated group. Of these, 307 metabolites were significantly different (P < 0.05). Compared with the control, 54 and 86 metabolites were significantly increased and decreased in the HZSO-1 group, respec-tively (P < 0.05). We speculated that the sterile fermentation filtrate of S. odorifera could mediate the carbohydrate and amino acid metabolism of H. marmoreus by influencing the pentose phosphate pathway (PPP) to increase the energy supply for the growth and development of the mycelium. The above results will further reveal the growth-promoting mechanism of S. odorifera on H. mar-moreus.

Atherosclerosis (AS) is a chronic progressive disease caused by various factors, and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) -protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.

Sepsis is a serious and life-threatening medical emergency associated with dysregulated host immune responses to infection. Like cerebral vascular or acute cardiovascular incidents, sepsis is considered a time-dependent condition having severe and long-term consequences on human health. Apart from organ support, prompt administration of appropriate antimicrobial therapy is crucial to limit the burden of complications related to sepsis in ICU patients. The management of septic patients requires comprehensive and multi-disciplinary strategies for an adequate diagnosis. Most of the ICU population receives empirical antibiotic therapy without having a confirmed diagnosis. The misuse of antibiotics in intensive care units may increase the possibility of developing multidrug resistance along with considerable ecological side effects. The first doses of empirical anti-microbial therapy are slightly higher, regardless of the presence or absence of organ dysfunction, which may upregulate the production of circulating pro-and-anti-inflammatory mediators, having negative effects on the general well-being of the patients. This notion supports the introduction of individualized antimicrobial approaches based on local patterns of resistance to ensure the appropriate dosage of empirical therapy, as well as to limit the emergence of multidrug resistance in advanced-care patients. The adequacy and treatment duration must be viewed at regular intervals for effective de-escalation, and novel diagnostic approaches must be introduced to improve the quality of care in the ICU population.

Till date there are three full length COVID 19 virus genome sequences available from India. The earlier two were reported from Kerala, Southern India and the more recent one has been reported from Gujarat, western part of India. In this paper we report two novel mutations in the Spike protein sequence of Gujarat’s isolate. These mutations are based on comparison with the original Wuhan sequence. The two mutations have been found to be located just upstream and downstream of the receptor binding domain (RBD). Out of these two one has also been found to affect the secondary structure of the S1 domain. Since both of these mutations lie near the receptor binding domain, they might influence the spike receptor interactions by changing the conformation of the spike protein S1 domain. These mutations are uniquely placed and might be important in the context of vaccine engineering and therapeutic interventions.

: 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

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

As an extension of the (univariate) Birnbaum-Saunders distribution, the Type II generalized crack (GCR2) distribution, built on an appropriate base density, provides a sufficient level of flexibility to fit various distributional shapes including heavy-tailed ones. In this paper, we develop a bivariate extension of the Type-II generalized crack distribution and study its dependency structure. For practical applications, several specific distributions, GCR2-Generalized Gaussian, GCR2-Student’s t and GCR2-Logistic, are constructed. The expectation-maximization algorithm is implemented to estimate the parameters in the bivariate GCR2 models. The model fitting results on the catastrophic loss dataset show that the bivariate GCR2 distribution base on the generalized Gaussian density fits the data significantly better than other alternative models.

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.

Elevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer’s disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanisms of aminoacyl-tRNA synthetases, and thus is a non-protein amino acid, it can be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to protein’s function and biological integrity, Hcy-thiolactone detoxifying enzymes – PON1, BLMH, BPHL – have evolved. This review provides an account of the biological function of these enzymes and of consequences of their impairments leading to phenotypes characteristic of AD.

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.

Background: Monogenic Alzheimer's disease (AD) has severe health and socioeconomic repercussions. Its rarest cause are presenilin 2 (PSEN2) gene mutations. We present two new cases with presumed PSEN2-AD, with unusual clinical and neuroimaging findings in order to provide more information on the pathophysiology and semiology of these patients. Methods: Women aged 69 and 62 years at clinical onset, marked by prominent behavioral and language dysfunction, progressing to severe dementia within three years. Neuroimaging, laboratory study, genetic testing. In addition, a systematic review of the PSEN2-AD were performed. Results: Neuroimaging revealed pronounced frontal white matter hyperintensities (WMH) and frontotemporal atrophy/hypometabolism. The genetic study unveiled PSEN2 variants: c.772G>A (p.Ala258Thr) and c.1073-2_1073-1del. Both cerebrospinal fluid (CSF) and experimental blood biomarkers shouldered AD etiology. Conclusions: Prominent behavioral and language dysfunction suggesting frontotemporal dementia (FTD) may be underestimated in the literature as a clinical picture in PSEN2 mutations. Thus, it may be reasonable to include PSEN2 in genetic panels when suspecting FTDL. PSEN2 mutations may cause striking WMH, arguably related with myelin disruption induced by amyloid accumulation.

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 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.

A sublingual vaccine comprising Poly(I:C) adjuvant and influenza HA antigen was evaluated for safety in both mice and macaque monkeys relative to its intranasal counterpart. Safety was assessed with harmful effects corresponding to upregulation of the inflammation-associated genes: Saa3, Tnf, IL6, IL1b, Ccl2, Timp1, C2, Ifi4, Aif1, Omp, Nos2, and/or Gzmb in mice and SAA2, TNF, IL6, IL1B, CCL2, TIMP, C2, AIF1, and GZMB in macaques. Quantitative gene expression analyses were performed using RT-qPCR with RNA samples from four tissues: olfactory bulb, pons, lung, tongue, and (submandibular) lymph node from both mice and macaques. In mice, the intranasally delivered vaccine markedly upregulated the inflammation-related genes in the olfactory bulb 1 day and 7 days after vaccination. The adverse effects of intranasal vaccination were also observed in macaques, however to a lesser extent than in mice. The intranasal vaccination also upregulated these genes in the pons of both mice and macaques. In contrast, the sublingual vaccine did not adversely affect the olfactory bulb or pons in either mice or macaques. The intranasally administered vaccine significantly upregulated these genes in the lungs only 1 day after vaccination, but not 7 days later, in both mice and macaques. We conclude that intranasal vaccination results in unfavorable side effects corresponding to upregulated inflammatory genes in the brain (olfactory bulb and pons). Sublingual vaccination, however, did not induce these side effects in either mice or macaque and was hence evaluated as safe.

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.

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..

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.

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.

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.

Recent research has implicated the gut microbiota in the development of lymphoma. Dysbiosis of the gut microbial community can disrupt the production of gut microbial metabolites, thereby impacting host physiology and potentially contributing to lymphoma. Dysbiosis-driven release of gut microbial metabolites such as lipopolysaccharides can promote chronic inflammation, potentially elevating the risk of lymphoma. In contrast, gut microbial metabolites, such as short-chain fatty acids, have shown promise in preclinical studies by promoting regulatory T-cell function, suppressing inflammation, and preventing lymphoma. Another metabolite, urolithin A, exhibited immunomodulatory and antiproliferative properties against lymphoma cell lines in vitro. While research on the role of gut microbial metabolites in lymphoma is limited, this article emphasizes the need to comprehend their significance, including therapeutic applications, molecular mechanisms of action, and interactions with standard chemotherapies. The article also suggests promising directions for future research in this emerging lymphoma and gut microbiome investigation field.

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.

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.

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.

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.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer’s disease (AD) patients leads to Aβ accumulation and formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is reduction of free Aβ level by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) of HSA to improve its affinity for Aβ. Here we develop this approach by bioinformatic search for the clinically approved AD-related LMWLs of HSA, followed by classification of the candidates according to the predicted location of their binding sites on HSA surface, ranking of the candidates, and selective experimental validation of their impact on HSA affinity for Aβ. The top 100 candidate LMWLs were classified into the five clusters. The specific representatives of the different clusters exhibit dramatically different behavior, with 3- to 13-fold changes in equilibrium dissociation constants for the HSA-Aβ40 interaction: prednisone favors HSA-Aβ interaction, mefenamic acid shows the opposite effect, while levothyroxine exhibits the bidirectional effects. Overall, the LMWLs of HSA chosen here provide a basis for drug repurposing for AD prevention, and for search for the medications promoting AD progression.

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.

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.

4E-BP2 deamidation significantly alters protein production in the brain and nervous system. It maintains the balance of protein production required for a healthy nervous system. Any imbalance in protein production in the brain and nervous system causes all neurodegenerative diseases. Discovering what causes 4E-BP2 deamidation only in neurons will make it possible to control this balance of protein production and cure neurodegenerative diseases such as memory loss, Alzheimer's, and Parkinson's. Alzheimer’s disease is caused by the absence of 4E-BP2 protein in the brain's neurons. This protein undergoes deamidation spontaneously only in the neurons and, in this way, controls the production of proteins in the neurons. This, in turn, determines whether or not Alzheimer’s and Parkinson’s disease start or progress. The purpose of this work is to discover the neurobiological mechanism that causes the deamidation reaction in the 4E-BP2 protein by performing immunoblotting in the retinal ganglia, the optic nerve, the dorsal root ganglia, the sciatic nerve, and the whole brain, extracted via dissection from 2-month-old, Wild-type male mice. The results showed that deamidation mainly occurs in the axons or axon-enriched regions of the optic nerve, the whole brain, and the sciatic nerve, confirming conclusively that axons are the critical factors behind the neurobiological mechanism of 4E-BP2 protein deamidation. The results confirm that they are also the reason why 4E-BP2 deamidation occurs only in neural tissue.

Nutritional management of depression has long been discussed due to the perceived benefit of a nutritional product having less side effects than pharmaceutical agents. Candidate nutrients for managing depression include Vitamin D, B-vitamins, tryptophan, branch chain amino acids, probiotics, omega-3 fatty acids, folate/methylfolate (aka Vitamin B9), and s-adenosylmethionine. This paper reviews three nutrients which have significant scientific support for the management of depression and have evidence of low levels in subjects with depression, and that correction of the nutritional deficiency provides clinical benefit. We present epidemiological evidence, mechanistic explanation and a review of interventional studies for these nutrients. Finally, relevant nutritional guidelines are presented with their conclusion for the role of each nutrient in the management of depression.

Intrinsic and extrinsic sensory elements influence our food experiences. However, most research in extrinsic multisensory aspects of food has centered on WEIRD (White, Educated, Industrialized, Rich, and Democratic) urban participants. This study breaks from this by investigating multisensory eating experiences in the context of Northern Norway, a region characterized by distinct seasonal shifts, harsh arctic weather, unique atmospheric phenomena (e.g., the midnight sun and northern lights), limited food growth opportunities, and a rich Sámi cultural heritage. Our exploratory research used participant observation and interviews, involving four researchers from diverse backgrounds who closely examined multisensory food experiences within four Northern Norwegian food-related tourism businesses, all infused with Sámi cultural elements. Four themes emerged: 1) Experience elements, involving elements associated with plants, animals, and non-animate objects. 2) Bipolar concepts, which refer to contradicting dimensions where experience elements varied, notably in the interplay between Sámi and Norwegian traditions. 3) Sensory stories, which highlight the narratives, enriching the eating experience with context, such as tales of dining under the captivating northern lights. 4) Values which indicate guiding principles shaping these experiences on a broader scale, emphasizing support for local traditions and culture. Our main contribution is the presentation of a new contextual framework of multisensory eating experiences which can be applicable to studying eating experiences in other contexts.

Radish (Raphanus sativus L.), a root vegetable belonging to the Brassicaceae family, is considered as one of the representative crops displaying sporophytic self-incompatibility (SSI). The utilization of a self-incompatibility system in F1 breeding can improve the efficiency of cross combinations, leading to a reduction in breeding time and aiding in the development of novel F1 varieties. The successful implementation of this system necessitates the rapid and accurate identification of S haplotypes in parental lines. In this study, we identified a total of 9 S haplotypes among 22 elite radish lines through Sanger sequencing. Subsequently, we obtained sequences for showing 95% similarity to 9 S haplotypes, along with sequences identified by other researchers using BLAST. Following this, multiple sequence alignment (MSA) was conducted to identify SRK and SLG sequence similarities, as well as polymorphisms within the class I, II groups. Subsequently, S haplotype-specific marker sets were developed, targeting polymorphic regions of SRK and SLG alleles. These markers successfully amplified each of 9 S haplotypes. these markers will play a crucial role in the rapid and precise identification of parental S haplotypes in the radish F1 breeding process, proving instrumental in the radish F1 purity test.

Brown-Séquard Syndrome (BSS) is a rare spinal cord injury characterized by asymmetrical motor and sensory dysfunction. Trauma to the spinal cord, particularly the hemi section, is the primary cause. Diagnosis involves a thorough medical history, physical examination, and imaging studies. Treatment focuses on stabilization, rehabilitation, and potential emerging therapies. This article provides a comprehensive overview of BSS, including its causes, symptoms, diagnosis, and treatment.

This article deals with the queueing-inventory system, composed of c junior servers, a senior server, two finite waiting halls, and an infinite orbit. On occasion, junior servers encounter challenges during customer service. In these instances, they approach the senior server for guidance in resolving the issue. Suppose the senior server is engaged with another junior server. The approaching junior servers await their turn in a finite waiting area with a capacity of c for consultation. Concerning this, we study the performance of junior servers approaching the senior server in the retrial queueing-inventory model with the two finite waiting halls dedicated to the primary customers and the junior servers for consultation. We formulate a level-dependent QBD process and solve its steady-state probability vector using Neuts and Rao’s truncation method. The stability condition of the system is derived, and the R matrix is computed. Optimum total cost has been obtained, and sensitivity analyses, which include expected total cost, waiting time of customers in waiting hall and orbit, number of busy servers, and fraction of successful retrial rate of the model, are done numerically.

In the present paper, we introduced a quadratically convergent Newton’s like normal S2 iteration method free from the second derivative for the solution of nonlinear equations permitting 3 f'(x) = 0 at some points in the neighborhood of the root. Our proposed method works well 4 when the Newton method fails. Numerically it has been verified that the Newton’s like normal 5 S-iteration method converges faster than Fang et al. method [A cubically convergent Newton-type 6 method under weak conditions, J. Compute. and Appl. Math., 220 (2008), 409-412]. We studied 7 different aspects of normal S-iteration method. Lastly, fractal patterns support the numerical 8 results and explain the convergence, divergence, and stability of method.

Lipid metabolism is clearly associated to Parkinson´s disease (PD). Although lipid homeostasis has been widely studied in multiple animal and cellular models as well as in blood derived from PD individuals, the cerebrospinal fluid (CSF) lipidomic profile in PD remains largely unexplored. In this study, we have characterized the CSF lipidomic imbalance between neurologically intact controls (n=10) and PD subjects (n=20). The combination of dual extraction with ultra-performance liquid chromatography-electrospray ionization quadrupole-time-of-flight mass spectrometry (UPLC-ESI-qToF-MS/MS) allowed to monitor 257 lipid species across all samples. Complementary multivariate and univariate data analysis pointed out that glycerolipids (mono-, di-, and triacylglycerides), saturated and mono/polyunsaturated fatty acids, primary fatty amides, glycerophospholipids (phosphatidylcholines, phosphatidylethanolamines), sphingolipids (ceramides, sphingomyelins), N-acylethanolamines and sterol lipids (cholesteryl esters, steroids) were significantly increased in the CSF of PD compared to control group. These results, despite the limitation of being obtained in a small population, demonstrate and extensive CSF lipid remodelling in PD, shedding new light on the deployment of CSF lipidomics as a promising tool to identify potential lipid markers as well as discriminatory lipid species between PD and other atypical parkinsonisms.

The search for novel brewing strains from non-brewing environments represents an emerging trend to increase genetic and phenotypic diversities in brewing yeast culture collections. Another valuable tool is hybridization, where beneficial traits of individual strains are combined in a single organism. This has been used successfully to create de novo hybrids from parental brewing strains by mimicking natural Saccharomyces cerevisiae ale x Saccharomyces eubayanus lager yeast hybrids. Here, we integrated both these approaches to create synthetic hybrids for lager fermentation using parental strains from niches other than beer. Using a phenotype-centered strategy, S. cerevisiae sourdough strains and the S. eubayanus x Saccharomyces uvarum strain NBRC1948 (also referred to as Saccharomyces bayanus) were chosen for their brewing aptitudes. We demonstrated that, in contrast to S. cerevisiae x S. uvarum crosses, hybridization yield was positively affected by time of exposure to starvation, but not by staggered mating. In laboratory-scale fermentation trials at 20°C, one triple S. cerevisiae x S. eubayanus x S. uvarum hybrid showed a heterotic phenotype compared with the parents. In 2L wort fermentation trials at 12°C, this hybrid inherited the ability to consume efficiently maltotriose from NBRC1948 and, like the sourdough S. cerevisiae parent, produced appreciable levels of the positive aroma compounds 3-methylbutyl acetate (banana/pear), ethyl acetate (general fruit aroma) and ethyl hexanoate (green apple, aniseed, and cherry aroma). Based on these evidences, the phenotype-centered approach appears promising for design of de novo lager beer hybrids and may help to diversify aroma profiles in lager beers.

The novel coronavirus (2019-nCoV) is a human and animal pathogen recently emerged in the city of Wuhan in Hubei province of China, causing a spectrum of severe respiratory illnesses. Corona viruses makes entry in to human cells through its spike (S) protein that binds to cell surface receptors. Wide spread of 2019-nCoV has been attributed to relatively high affinity of S protein to its receptor. Although S protein is a highly importantdrug target, unavailability of a high-resolution crystal structure and solvent accessible binding surface has made it a tedious target for current rapid virtual screening. A homology model of the receptor binding domain (RBD) of 2019 -n CoV S protein that is reasonably acceptable for drug screening was prepared using a high resolution crystal structure of SARS corona virus (SARS CoV)S protein. Data obtained from RBD- receptor docking experiments and published molecular dynamics experiments were used to map a RBD-receptor interaction hotspot that can be used for designing small molecule inhibitors. The hot spot was then used for virtual screening of more than 3000 drugs approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Two anthracycline class drugs (zorubicin and aclarubicin) and a food dye (E 155) were predicted to be potent inhibitors of RBD – receptor interaction. Results of present study provide evidence for the potential of these compounds asprophylactic medications or for use to reduce disease severity of COVID -19.

Longevity risk constitutes an important risk factor for life insurance companies and it can be managed through longevity-linked securities. The market of longevity-linked securities is at present far from being complete and does not allow to find a unique pricing measure. We propose a method to estimate the maximum market price of longevity risk depending on the risk margin implicit within the calculation of the technical provisions as defined by Solvency II. The maximum price of longevity risk is determined for a survivor forward (S-forward), an agreement between two counterparties to exchange at maturity a fixed survival-dependent payment for a payment depending on the realized survival of a given cohort of individuals. The maximum prices determined for the S-forwards can be used to price other longevity-linked securities, such as q-forwards. The Cairns-Blake-Dowd model is used to represent the evolution of mortality over time, that combined with the information on the risk margin, enables us to calculate upper limits for the risk-adjusted survival probabilities, the market price of longevity risk and the S-forward prices. Numerical results can be extended for the pricing of other longevity-linked securities.

The thermal surface properties of graphenes and carbon materials are of crucial importance in chemistry of materials, chemical engineering, and many industrial processes. (1) Background: The determination of these surface properties is carried out using inverse gas chromatography at infinite dilution which leads to the retention volume of organic solvents adsorbed on solid surfaces. This experimental and fundamental parameter actually reflects the surface thermodynamic interactions between injected probes and solid substrates. (2) Methods: The London dispersion equation and the Hamieh thermal model were used to quantify the London dispersive and polar surface energy of graphenes and carbon fibers as well their Lewis acid-base constants by introducing the coupling amphoteric constant of materials. (3) Results: The London dispersive and polar acid-base surface energies, the free energy of adsorption, the polar enthalpy and entropy, and the Lewis acid-base constants of graphenes and carbon materials were determined. (4) Conclusions: it was showed that graphene exhibited the highest values of London dispersive surface energy, polar surface energy, and Lewis’s acid-base constants. These highest characteristics of graphene justify its great potentiality and uses in many industrial applications.

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.

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.

We present a simple proof of the well-known axiomatic characterization of state-salient decision rules on the domain of all strict preference profiles, using Pareto property and Global Independence of Irrelevant Alternatives. Our proof appeals to Sen’s Impossibility Theorem and an extract from a proof of the same theorem, that is available in an earlier paper of this author.

Objective: Fludeoxyglucose F18 positron emission tomography (FDG PET) can give early clues for diagnosing Alzheimer’s disease (AD). Our objective was to use the same scan to predict Apolipoprotein E4 (ApoE4), known to be a risk factor. A second objective was to determine the brain regions and imaging features associated with this gene allele that can potentially help elucidate the mechanisms of the disease and better comprehend the images. Method: We employed data from 112 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). PET and structural MRI data were co-registered with ANTx, and the Freesurfer tool delineated 95 whole brain, 19 hippocampal, and 9 amygdala regions. Using PyRadiomics we extracted 120 radiomic features from these segments. We employed a hybrid feature selection strategy. The HistGradientBoosting (HGB) classifier was evaluated using stratified five-fold cross-validation. Results: The proposed radiomics model predicted the homozygous ApoE4 genotype, with an AUC of 0.945 an accuracy of 0.875, a sensitivity of 0.914, and a specificity of 0.838. Reducing the feature set to seven key features resulted in a slightly decreased performance (AUC: 0.889). The mean values of the features showed statistically significant (p<0.05) incremental deterioration between different groups of homozygous ApoE4 carriers. Conclusion: Our findings underscore the critical role of specific brain regions and associated features in differentiating ApoE4 carriers. The hippocampus, entorhinal cortex, amygdala, thalamus, and pars orbitalis exhibited significant associations with the ApoE4 genotype. By employing SHAP analysis, we identified key features driving model predictions, enhancing interpretability, and providing insights into the underlying pathophysiology.

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.

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.

Finding, safe and reliable alternatives to fungicides is one of the most actual challenges in agriculture. In this regard, our experiment investigated the effectiveness of different elicitors, botanical extracts and essential oils to control grey mould (Botrytis cinerea) and powdery mildew (Podosphaera aphanis) on strawberry plants. Furthermore, the defence mechanisms activated in plants after treatments were investigated. The trial was conducted in field conditions under plastic tunnel with strawberry plants ‘Elsanta’. In the first experiment, a group of strawberry plants was treated before flowering with elicitors [acibenzolar-S-Methyl – (BTH), chitosan], botanical extracts (seaweed extract, alfalfa hydrolysate) and essential oils (thyme and juniper) to evaluate their ability to reduce the incidence of grey mould infection on flowers. In the second experiment, another group of plants was treated before and after experimental inoculation with P. aphanis. Results indicated that the incidence of flower infected by B. cinerea was significantly reduced by thyme and juniper essential oils, showing values that were not significantly different from the commercial fungicide penconazole (positive control). As a consequence, final yield of essential oil-treated plants was +27% higher as compared to control. No significant differences emerged for other tested products against grey mould. However, gene expression analysis showed an up-regulation of FaEDS1, FaLOX and PR gene expression (FaPR1, FaPR5, FaPR10) in leaves treated with BTH. The other tested natural substances also elicited defence-related genes, however at a lower level than BTH. In the experiment, all treatments applied prior inoculation significantly reduced the incidence and severity of powdery mildew as compared to control. At 28 days after inoculation, chitosan and thyme essential oil applications performed similarly to their positive controls (BTH and penconazole, respectively), showing a significant reduction of disease incidence (by -84 and -92%) as compared to control. Post-inoculum application of essential oils showed similar effective action to fungicide (penconazole) in reducing incidence and severity of powdery mildew. These results indicate that the tested substances could be used as alternatives to fungicides for the control of grey mould and powdery mildew in strawberry, therefore representing a valuable tool for the control of these fungal diseases under the framework of the sustainable agriculture.

Alzheimer’s disease (AD) and vascular dementia (VaD) together contribute to almost 90% of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in Alzheimer’s disease, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. We thus highlight here the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress, inflammation and demyelination and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

The surface thermodynamic properties of polymers and copolymers modified by supramolecular structures are very used in several industrial processes, such as selective adsorption, paints, coatings, colloids, and adhesion applications. Background: Inverse gas chromatography at infinite dilution was proved to be the best technique to determine the surface properties of solid surfaces by studying the adsorption of some model polar and non-polar organic molecules adsorbed on solid surfaces by varying the temperature. Methods: The retention volume of adsorbed solvents is a precious parameter to obtain the London dispersive and polar free energies and the London dispersive surface energy of styrene–divinylbenzene copolymer modified by supramolecular structure of melamine using the Hamieh thermal model and our new methodology consisting in the separation of the two polar and dispersive free energy of interaction. This led to the determination of the polar acid and base surface energy, and the Lewis’s acid-base constants of the various solid materials. Results: all surface energetic properties of styrene–divinylbenzene copolymer modified by melamine at different percentages were determined as a function of temperature, following our new methodology. Conclusions: It was observed that the styrene–divinylbenzene copolymer exhibited the highest London dispersive surface energy which decreased when the melamine percentage increased. All materials presented higher Lewis’s basicity and this Lewis’s basicity increased with the percentage of melamine.

We study here what can be learned from our experience with COVID-19 vaccination for an initially naïve population, that can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE), waning effectiveness over time, and what we should expect about VE and waning from a future pathogen. As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through August 15, 2022 reporting VE against four endpoints: any infection, symptomatic infection, hospitalization, and death, for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S). The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines initially outperformed the viral vector vaccines. A third “booster” dose, roughly six months after the primary doses, substantially reduced symptomatic infection, severe disease, and mortality, and in hindsight should be seen as part of the normal vaccination schedule.

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.

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.

Cancer immunobiology is one of the hot topics of discussion amongst researchers today, and immunotherapeutic modalities are among the selected few emerging approaches to cancer treatment that have exhibited a promising outlook. However, immunotherapy is not a new kid on the block; it has been around for centuries. The origin of cancer immunotherapy in modern medicine can be traced back to the initial reports of spontaneous regression of malignant tumors in some patients following an acute febrile infection, at the turn of the twentieth century. This review briefly revisits the historical accounts of immunotherapy, highlighting some of the significant developments in the field of cancer immunobiology, that have been instrumental in bringing back the immunotherapeutic approaches to the forefront of cancer research. Some of the topics covered are: Coley's toxin - the first immunotherapeutic; the genesis of the theory of immune surveillance; discovery of T-lymphocytes and dendritic cells and their roles; the role of tumor antigens; relevance of tumor microenvironment; anti-tumor (therapeutic) ability of Bacillus Calmette Guerin; Melacine - the first therapeutic vaccine engineered; theories of immunoediting and immunophenotyping of cancer; and Provenge – the first FDA approved therapeutic vaccine. In this review, head and neck cancer has been taken as the reference tumor, for narrating the progression of cancer immunobiology, particularly, for highlighting the advent of immunotherapuetic agents.

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.

In a systematic explorative study of genetic patterns on chromosome 19, we discovered a pattern comprised of 23 SNP alleles that is significantly associated with late-onset Alzheimer’s disease (AD). This association is validated using two independent data sets. The pattern includes THOP1, which has a long and disputatious relationship with AD. It also spans SLC39A3 and SGTA and is upstream from DIRAS1. We utilized population data to observe the frequencies of this genetic pattern for 11 different ancestries and note that it is highly common for Europeans and relatively infrequent for Africans. This research provides a distinct genetic signature for AD risk as well as insights into the complicated relationship between this disease and THOP1.

A relativistic positioning system is a set of four emitters broadcasting their proper times by means of light signals. The four emitter times received at an event constitute the emission coordinates of the event. Covariant quantities associated with relativistic positioning systems are analysed relatively to an observer in Minkowski space-time by splitting them in their relative space-like and time-like components. The location of a user in inertial coordinates from a standard set of emission data (emitted times and satellite trajectories) is solved in the underlying 3+1 formalism. The analytical location solution obtained by Kleusberg for the GPS system is recovered and interpreted in a Minkowskian context.

Vectorial Boolean functions and codes are closely related, and each corresponding domain gives been to each other. On the one hand, various requirements of binary linear codes are needed for their theatrical interests but, more importantly, for their practical applicants (such as few-weight codes or minimal codes for secret sharing, locally recoverable codes for storage, etc.). On the other hand, various criteria and tables have been introduced to analyse the security of S-boxes that are related to vectorial Boolean functions, such as the Differential Distribution Table (DDT), the Boomerang Connectivity Table (BCT), and the Differential-Linear Connectivity Table (DLCT). In previous years, two new tables have been proposed for which the literature was pretty abundant: the $c$-DDT to extend the DDT and the $c$-BCT to extend the BCT. In the same vein, we propose extended concepts to study further the security of vectorial Boolean functions, especially the $c$-Walsh transform, the $c$-autocorrelation, and the $c$-differential-linear uniformity, and its accompanying table, the $c$-Differential-Linear Connectivity Table ($c$-DLCT). We study these properties of the novel functions at their optimal level concerning these concepts and describe the $c$-DLCT of the crucial inverse vectorial (Boolean) function case. Finally, the derived functions could lead to new families of binary minimal codes, as the recent achievements on minimal codes from low differential uniformity. We draw new avenues for future research toward linear code designs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, represents a serious threat to public health. The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry into host cells and is heavily glycosylated. In this study, we systemically analyzed the roles of 22 putative N-linked glycans in SARS-CoV-2 S protein expression, membrane fusion, viral entry, and stability. Using α-glycosidase inhibitors, castanospermine and NB-DNJ, we confirmed that disrupting the N-linked glycosylation process blocked the maturation of the S protein, leading to impairment of S protein-mediated membrane fusion. Single substitution of each of the 22 N-linked glycosylation sites with glutamine revealed that 9 out of the 22 N-linked glycosylation sites were critical for S protein folding and maturation, resulting in reduced S protein-mediated cell-cell fusion and viral entry. Of note, N1074Q mutation markedly affected S protein stability and induced significant receptor-independent syncytium (RIS) formation in HEK293T/hACE2-KO cells, and removal of the furin-cleavage site partially compensated instability of N1074Q mutation. Although the corresponding mutation in the SARS-CoV S protein (N1056Q) did not induce RIS in HEK293T cells, the mutants N669Q and N1080Q exhibited increased fusogenic activity and induced syncytia formation in HEK293T cells. Therefore, N-glycans on the SARS-CoV and SARS-CoV-2 S2 subunits are of great importance in maintaining the prefusion state of the S protein. The study revealed the critical roles of N-glycans in S protein maturation and stability, which have implications for the design of vaccines and anti-viral strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of corona-virus disease 19 (COVID-19) and employs angiotensin-converting enzyme 2 (ACE2) as the recep-tor. Although the expression of ACE2 is crucial for cellular entry, we found that the interaction of ACE2 with the Spike (S) protein in the same cells led to its downregulation through degradation in the lysosomal compartment via the endocytic pathway. Interestingly, the ability of the S protein from previous variants of concern (VOCs) to downregulate ACE2 was variant-dependent and correlated with disease severity. The S protein from the Omicron variant, associated with milder disease, exhibited a lower capacity to downregulate ACE2 than that of the Delta variant, which is linked to a higher risk of hospitalization. Chimeric studies between the S proteins from the Delta and Omicron variants revealed that both the receptor-binding domain (RBD) and S2 subunit played crucial roles in the reduced ACE2 downregulation activity observed in the Omicron var-iant. In contrast, three mutations (L452R/P681R/D950N) located in the RBD, S1/S2 cleavage site, and HR1 domain were identified as essential for the higher ACE2 downregulation activity ob-served in the Delta variant than that in the other VOCs. Our results suggested that dysregulation of the renin-angiotensin system due to the ACE2 downregulation activity of the S protein of SARS-CoV-2 may play a key role in the pathogenesis of COVID-19.

Recently, we demonstrated the validity of anomalous numbers law, known as Newcomb-Benford´s law, at the mammalian neuromuscular transmission, considering different extracellular calcium concentrations . The present work continues to examine how alterations in extracellular solution modulate the first digit law in the context of the spontaneous release of acetylcholine from the neuromuscular junction. We investigated if the intervals of miniature potentials collected at the neuromuscular junction obey the law in a hyperkalemic environment. The analysis showed that the interval between the miniature potentials at high potassium concentrations follows Newcomb-Benford´s law. Also, our data allowed us to uncover a conformity fluctuation as a function of the number of intervals of the miniature potentials. Finally, we discuss the biophysical implications of the present findings.

Polymyositis is a rare condition with an unknown etiology occurring more frequently in adult women. There is a lack of evidence on the coexistence of PM and CMV infection in a patient with Hashimoto Thyroiditis hypothyroidism. However, the increasing incidence of CMV infection and autoimmune diseases overlapping points out a relationship, while the association direction remains unclear. Case outline: A 32-year-old woman recently treated for HT hypothyroidism was admitted to the hospital two weeks after being treated for common flu by the family doctor, complaining about a worsening condition with muscle pain, weakness, frequent falls, and fatigue. The first tests showed a normalized thyroid function, with elevated values of troponin and serum creatinine kinase (KC). The immunological tests revealed the presence of a high titer of CMV IgG antibodies and raised levels of CMV DNA. Pelvis MRI images demonstrated markedly elevated signals on the STIR sequences in the pelvis, thighs, and calves, indicating active and severe multifocal myositis. The diagnosis of PM was confirmed with the muscle biopsy on day 7 of hospitalization. The patient showed significant improvements within two weeks after the medical therapy and physiotherapy.

The humoral response of the COVID-19 vaccine varies from person to person. It largely depends on prior SARS-CoV-2 infection, obtaining an adequate immune response, and leaving a trace of changing antibody concentration over time. We retrospectively analyzed five clinical cases from selected patients and employees of the oncology hospital. All mild COVID-19 convalescents received the BNT162b2-Comirnaty mRNA vaccine three or four times. The levels of SARS-CoV-2 IgM- and IgG-specific antibodies, as well as S-RBD antibodies, were analyzed for two years. The concentration of antibodies was assessed in the laboratory using the chemiluminescent immunoassay CLIA, MAGLUMI. Results: (1) Active autoimmune disease stabilized the level of IgG-specific antibodies after systemic mRNA vaccination for at least six months. (2) Post-vaccination IgG and S-RBD levels decreased when vaccination was performed within three months of onset. (3) The booster dose administered only increased the S-RBD antibody levels. Declining IgG-specific antibodies were observed. (4) The S-RBD IgG levels were not correlated with the SARS-CoV-2 IgG levels in the vaccinated convalescents. (5) Subsequent reinfection with SARS-CoV-2 after vaccination three times released a more significant specific antibody response. Based on the collected data, we suggest that monitoring S-RBD antibodies is sensitive but not equivalent to a specific humoral response for SARS-CoV-2 IgG. We suggested that administering at least three doses of the mRNA vaccine should serve as the basis for immunization. The three-month interval may be the best alternative to an immunization schedule for non-immunocompromised people.

The relationship between Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, we have analyzed the differential palmitome present in the cerebral cortex of PD patients compared to controls (n=4 per group) to better understand the role of protein palmitoylation in PD and the pathways altered in this disease. Data-mining of the cortical palmitome from PD patients and controls has allowed to: i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls, ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes, and iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we have partially characterized the altered palmitome in the cortex of PD patients which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study points out that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease.

Abstract The present work was designed to investigate antiviral potential of novel mono and oligomeric Chitosan derivatives through in-silico approaches to find potent broad-spectrum anti-viral and promising drug candidates against SARS-CoV-2 and augmentation of their mode of action. Chitosan biopolymer and its derivatives were screened virtually against spike glycoprotein and human ACE2 receptor of nCoV-19. HTCC a polymeric Chitosan has been reported to interact with the corona viral Spike (S) protein and blocks its interaction with ACE2 receptor. Better biocompatibility, structural correlations, variation in degree of decetylation and molecular weight of modified Chitosan derivatives are the key attributes for enhancement of anti-viral activity. The Chitosan derivatives constructively interact with viral S protein. N-Carboxy methyl Chitosan (NCMC) among the Chitosan derivatives displayed efficient binding affinity. NCMC, when compared to mHTCC, a monomeric Chitosan for its interaction with the S protein, RBD site and ACE2 receptor, displayed efficient binding affinity with binding energy of -7.9, -6.3 and -7.4; -6.2, -4.8 and -5.5 Kcal/mol respectively. The interaction of S protein with ACE2 and ligand mHTCC-S protein complex and NCMC-S protein complex with ACE2 was calculated through flexible docking resulted in efficient reduction of binding energy from -901.2kJ/mol to -765.06kJ/mol and-814.72kJ/mol respectively, elucidated that the binding affinity of the viral S protein for its receptor ACE2 decreases in the presence of NCMC/mHTCC. The computational study envisages the antiviral efficiency of NCMC, mHTCC and biocompatible Chitosan derivatives for the first time,as preventive intervention against Covid-19.

Critical care of neonates involves substantial usage of antibiotics and exposure to multidrug resistant (MDR) nosocomial pathogens. These pathogens are often exposed to sub-MIC doses of antibiotics which might result in a range of physiological effects. Therefore, to understand the outcome of sub-inhibitory dosage of antibiotics on Staphylococcus populations, nasal swab specimens were collected from 34 neonates admitted to the Sick Newborn Care Unit between 2017-2018, a total of 41 non-repetitive isolates were included in this study. Staphylococcus haemolyticus was the prevalent species (58.54%) with high non-susceptibility to cefotaxime (CTX) (79.16%), gentamicin (87.50%), and meropenem (54.17%). Biofilm forming abilities of S. haemolyticus isolates in the presence of sub-optimal CTX (30μg/mL), the predominantly prescribed β-lactam antibiotic, were then determined by crystal violet assays and extracellular DNA (eDNA) quantitation. CTX was found to significantly enhance biofilm production among the non-susceptible isolates (p-valueWilcoxin test- 0.000008) with increase in eDNA levels (p-valueWilcoxin test- 0.000004). Additionally, no changes in non-susceptibility were observed among populations of two MDR isolates, JNM56C1 and JNM60C2 after >500 generations of growth in the absence of antibiotic selection in vitro. These findings demonstrate that sub-MIC concentration of CTX induces biofilm formation and short-term non-exposure to antibiotics does not alter non-susceptibility among S. haemolyticus isolates.

This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDR) during the training period before a marathon race. Thirty-six healthy male LDR (37.0±5.3 years; 174.0±7.0 height; BMI: 23.8±2.8; VO2-peak: 56.5±7.3 mL·kg-1·min-1) were separated into two groups according to previous training level: high-training (HT, n=16) ≥100 km·week-1 and low-training (LT, n=20) ≥70 and &lt;100 km·week-1. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48-hr without exercising) the week before the race. HT group showed higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p&lt;0.05, for both), also higher levels of ROCK activity were found in LDR (HT=6.17±1.41 vs CTR=1.64±0.66 (p&lt;0.01); vs LT=2.74±0.84; (p&lt;0.05)). In LDR a direct correlation between ROCK activity levels and LVMi (r=0.83; p&lt;0.001), and LAVi (r=0.70; p&lt;0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography.

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.

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.

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.

Mono-crop plantation widely found in the world and dominated by few species such as Eucalyptus, Pinus and Tectona. While they lack diversified product, negative to environmental service and limited forest product for local use. The experiment was designed to evaluate the impact of mixed plantings on the early growth performance of the E. globulus tree species. The treatments included one monoculture of E. globulus and a combination of the plant with three other native and one foreign tree species. In four consecutive years after plantation, height, root collar diameter, DBH and leaf/branch count were measured. Following two years of out planting, the survival rates of seedlings were determined. Destructive sampling was applied to measure biomass of E. globulus. The growth performance of E. globulus in mixed plantations was compared to that of trees produced in pure plantations. The findings showed that there were no significant variations in growth parameters across the treatments. Following two years of out planting, the survival rates of seedlings were determined. The growth performance of E. globulus in mixed plantations was compared to that of trees produced in pure plantations. The findings showed that there were no significant variations in growth parameters across the treatments. The survival rate of E. globulus was good, ranging from 75 to 96.8%. Similarly, the growth performance of E. globulus's root collar diameter was larger even if the trial did not reveal a significant difference between the treatments for height. In comparison to other treatments, the one that included junipers and E. globulus had a higher mean height throughout the course of three years (1.28, 2.53, and 6.12 meters, respectively), as well as a lower RCD in the first and third years (1.3 and 5.34 cm). At year four, E. globulus attain higher in Height and DBH with high growth rate in mixed plantations compared to pure stands. The relative yield of E. globulus in pure stands compare to mixed stands greater than 1. Above and below ground biomass and carbon density of E, globulus is comparable in all treatment. Overall, the study's findings confirm that planting E. globulus improves its mingling with the examined tree species. Such studies ought to be conducted again over a longer time frame in order to examine the effects at a later stage and recommend technologies for broader implementation.

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.

Composites of Ag and TiO2 nanoparticles on cotton fabrics were synthetized in-situ by sono-chemical and hydrothermal methods achieving the successive formation of Ag-NPs and Ti-NPs directly on the fabric. The impregnated fabrics were characterized by ATR-FTIR spectroscopy, high resolution microscopy (HREM), scanning electron microscopy coupled with Ener-gy-dispersive X-ray spectroscopy (SEM-EDS), Raman, photoluminescence, UV-vis and DRS spectroscopies and by tension tests. Results showed the successful formation and impregnation of NPs on the cotton fabric, with a negligible leaching of NPs after several washing cycles. The photocatalytic activity of supported NPs was assessed by the degradation of methyl blue dye (MB) under solar and UV irradiation revealing improved photocatalytic activity of the Ag-TiO2/cotton composites due to a synergy of both Ag and TiO2 nanoparticles. This behavior is attributed to a diminished electron-hole recombination effect in the Ag-TiO2 cotton samples. The biocide activity of these composites on the growth inhibition of Staphylococcus aureus (Gram+) and Escherichia coli (Gram-) was confirmed, revealing interesting possibilities for the utilization of the functionalized cotton fabric as protective cloth for medical applications.

Recently, many authors have been interested to introduce fuzzy implications over t-norms and t-conorms. In this paper, we introduce (S,N) and residuum fuzzy implication for Dubois t-norm and Hamacher's t-norm. Also, new concepts so-called (T,N) and residual fuzzy co-implication in dual Heyting Algebra are investigated. Some examples as well as application are discussed as well.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

Viral infections leading to inflammation have been implicated in several common diseases such as Alzheimer’s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissoci-ated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D. We observed that differentially expressed genes (DEGs) in HSV-1-infected sc-islets were enriched for genes associated with several autoimmune diseases, most significantly T1D but also rheumatoid arthritis, psoriasis, Crohn’s disease, and multiple sclerosis, whereas DEGs in HSV-1-infected dcOrgs were exclusively enriched for genes associated with AD. ACV treatment of sc-islets did not rescue transcript expression of autoimmune disease-associated genes. Finally, we identified gene ontology categories that were enriched for DEGs that were in common across, or unique to, viral treatment of dcOrgs and sc-islets, such as categories involved in the transferase complex, mitochondrial and autophagy function. Collectively, this studies pro-vide insight to the molecular effects of inflammation in AD and T1D.

This perspective discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever, persistent severe cough, change of voice, loss of taste and smell, epigastric pain, nausea, vomiting, diarrhea, generalized malaise and marked bone aches in adults including the high risk groups. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.