The production of recombinant enzymes, mainly used for obtaining pure and functional target molecules, holds significant importance in modern biotechnology. This study aimed to produce recombinant α-amylases (Amy3500 and Amy1974), derived from B. amyloliquefaciens MDC1974 and B. subtilis MDC3500 respectively, using the pBE-S shuttle vector, and to characterize them. Both α-amylase genes were molecularly cloned into the E. coli/B. subtilis pBE-S shuttle vector, both with (Amy1974sig and Amy3500sig) and without their own signal peptides (Amy1974 and Amy3500), along with a signal peptide originating from the plasmid, and tested in flask fermentations. For recombinant Amy3500, the amylase variants resulted in similar levels of volumetric activity (700-750 U/mL). In contrast, the expression of Amy1974 nearly doubled compared to Amy1974sig with double signal peptides, reaching 2000 U/mL. The SDS-PAGE estimated the molecular weight of Amy1974 α-amylase to be 54.6 kDa, which was in accordance with the theoretical molecular mass calculations. However, the estimated molecular weight of Amy3500 amylase was significantly reduced when exiting the producer cells. Ca2+ had no significant activating effect on the activities of Amy1974 amylase and Amy3500 amylase, likely due to its tight binding to the protein scaffold. Both enzymes exhibited broad activity peaks between 45-70°C, with a maximum at 65°C. The Amy1974 and Amy3500 α-amylases demonstrated broad pH optima and pH-dependent thermostability, with optimum pH values at 6.5 and 5.8, and thermal stability peaks at pH 7.6 and 5.9, respectively. Both α-amylases displayed high relative activity against various starches, including corn amylopectin and potato amylose, while showing comparatively lower activity towards cyclodextrins. The Amy1974 amylase converts starch to dextrins of varying lengths, whereas Amy3500 almost entirely converts starch into glucose.

Research on titanium oxo complexes (TOCs) are usually focused on their structure and photocatalytic properties. Findings from these investigations spurred our interest in exploring also their potential biological activities. In this study, we focused on the synthesis and structure of a compound with the general formula [Ti8O2(OiPr)20(man)4] (1), which was isolated from the reaction mixture of titanium(IV) isopropoxide with mandelic acid (Hman) in a molar ratio of 4:1. The structure (1) was determined using single-crystal X-ray diffraction, while spectroscopic studies provided insights into its physicochemical properties. To assess the potential practical applications of (1), its microcrystals were incorporated into a polymethyl methacrylate (PMMA) matrix, yielding composite materials of the type PMMA + (1) (2 wt.%, 5 wt.%, 10 wt.%, and 20 wt.%). The next stage of our research involved the antimicrobial activity evaluation of the obtained materials. Investigations carried out demonstrated antimicrobial activity of pure (1) and its composites (PMMA + (1)) against both Gram-positive and Gram-negative strains. Furthermore, MTT tests conducted on the L929 murine fibroblast cell line confirmed the lack of cytotoxicity of these composites. Our study identified (1) as a promising antimicrobial agent, also for producing composite coatings.

Hypertension (HT) is a very common risk factor and a frequent cause of morbidity and mortality worldwide mainly due to much increase in overweight (OW) and obesity that manifests in various forms of cardiovascular disease (CVD). There are a number of factors that may cause overweight hypertension (OHT). However, we planned to conduct the present work to study the HT and OHT men for finding the variation, interrelationship and association of important cytokines mainly serum leptin (Lep) and tumor necrosis factor-alpha (TNF-α), serum testosterone (ST), total cholesterol (TC) and inflammatory status by measuring interleukin-6 (IL-6). Three groups of subjects, the normal controls (NC; n:98; age range: 51-60 years), HT (n: 97; age range: 51-60 years) subjects, and OHT (n: 97; age range: 51-60 years) subjects were studied. Comparisons for Lep, ST, TNF-α, IL-6 and TC levels for the subject groups showed significant variations. The ST indicated significant difference only for NC vs. OHT. The IL-6 gave significant difference for NC vs. OHT and HT vs. OHT. The one-way ANOVA showed significant difference among groups for BMI, TC, IL-6, TNF-α, ST and Lep levels. Significant positive linear correlation for all groups among Lep, TNF-α, IL-6 and TC were found. The ST against TC for HT and OHT groups presented non-significant negative linear correlations. The ST showed significant negative linear correlation with other variables. Conclusively, the present study uncovers the interactive impact of serum leptin, TNF-α, testosterone, total cholesterol and IL-6 in hypertensive and overweight-related hypertensive men.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

Eurycomanone and eurycomalactone are known quassinoids present in the roots and stems of Eurycoma longifolia. These compounds had been reported to have cytotoxic effects, however, their mechanism of action in a few cancer cell lines have yet to be elucidated. This study was aimed to investigate the anti-cancer effects and mechanisms of action of eurycomanone and eurycomalactone in cervical (HeLa), colorectal (HT29) and ovarian (A2780) cancer cell lines via Sulforhodamine B assay. Their mechanism of cell death was evaluated based on Hoechst 33342 assay and in silico molecular docking toward DHFR and TNF-α as putative protein targets. Eurycomanone and eurycomalactone exhibited in vitro anti-cancer effects manifesting IC50 values of 4.58 ± 0.090 µM and 1.60 ± 0.12 µM (HeLa), 1.22 ± 0.11 µM and 2.21 ± 0.049 µM (HT-29), and 1.37 ± 0.13 µM and 2.46 ± 0.081 µM (A2780) respectively. They induced apoptotic cancer cell death in dose- and time-dependent manners. Both eurycomanone and eurycomalactone were also predicted to have good inhibitory potential as demonstrated by the docking into TNF-α with binding affinity of -8.83 and -7.51 kcal/mol, respectively, as well as into DHFR with binding affinity results of -8.05 and -8.87 kcal/mol, respectively. These results support the evidence of eurycomanone and eurycomalactone as anti-cancer agents via apoptotic cell death mechanism that could be associated with TNF-α and DHFR inhibition as among possible protein targets.

Plant flavonoids have increasingly paid a close attention to for new antimicrobial agents or adjuvants. In our previous work, it was confirmed that the cell membrane is the major site of plant flavonoids acting on the gram-positive bacteria, and which likely involves the inhibition of the respiratory chain. Inspired by the similar structural and antioxidant characters of plant flavonoids to MKH₂, we deduced that the quinone pool is probably a key target of plant flavonoids inhibiting gram-positive bacteria. To verify this, twelve plant flavonoids with six structural subtypes were preliminary selected, and their MICs against gram-positive bacteria were predicted from the antimicrobial quantitative relationship of plant flavonoids to gram-positive bacteria. The results showed they have different antimicrobial activities. After their MICs against S. aureus were determined using broth microdilution method, nine compounds with the MICs ranged from 2 to 4,096 μg/mL or more than 1,024 μg/mL were eventually selected, and then their MICs against S. aureus were determined interfered with different concentrations of MK-4 and the MKs extracted from S. aureus. The results showed that the greater the antibacterial activities of plant flavonoids were, the more greatly their antibacterial activities decreased along with the increase of the interfering concentrations of MK-4 (from 2 to 256 μg/mL) and MK extract (from 4 to 512 μg/mL), and while those, with the MICs equal to or more than 512 μg/mL, decreased a little or remained unchanged. Especially, under the interference of MK-4 (256 μg/mL) and MK extract (512 μg/mL), the MICs of α-mangostin, a compound with greatest inhibitory activity to S. aureus in these twelve plant flavonoids, increased by 16 times and 8 to16 times, respectively. Based on these above, it was proposed that the quinone pool is a key target of plant flavonoids inhibiting gram-positive bacteria, and which likely involves multiple mechanisms including some enzyme and non-enzyme inhibitions.

In this paper, the deformation and phase transformation of disorder α phase at (α + γ) two phase region in as-forged Ti-44Al-8Nb-(W, B, Y) alloy are investigated by hot compression and hot packed rolling. Detailed microstructural evolution demonstrates that the as-deformed microstructure is significantly affected by deformation conditions. The mircrostructure differences are mainly due to temperature drop and strain rate. The evolution of α lamelae into α grains is detailed descripted. Moreover, the disorder α lamellae can also be decomposed into some new α grains by the assisted decomposition mechanism of γ grains. Microstructure evolution model of current TiAl alloy at 1250 °C during hot rolling is built.

Plukenetia volubilis is an underutilized oilseed crop native to the Amazon basin, where it has been utilised by humans since Incan times. The large seeds contain approx. 45–50 % lipid, of which approx. 35.2–50.8 % is α-linolenic acid (C18:3 n-3, ω-3) and approx. 33.4–41.0 % is linoleic acid (C18:2 n-6, ω-6), the two essential fatty acids required by humans. The seeds also contain 22–30 % protein and have antioxidant properties. Due to its excellent nutritional composition and good agronomic properties, it has attracted increasing attention in recent years, and cultivation is expanding. When considering current global challenges, a reformation of our food systems is imperative in order to ensure food security, mitigation of climate change, and alleviation of malnutrition. For this purpose, underutilized crops may be essential tools, which can provide agricultural hardiness and reduced need for external inputs, climate resilience, diet diversification, and improved income opportunities for smallholders. Plukenetia volubilis is a promising up and coming crop in this regard and has considerable potential for further domestication; it has an exceptional oil composition, good sensory acceptability, is well suited for cultivation, and has numerous potential applications in, e.g. gastronomy, medicine, and cosmetics.

The expanding use of devices emitting Pulsed Telecommunication Signals (PTS) has launched a serious debate over the possible effects of electromagnetic radiation (EMR) on living organisms. Our previous work has indicated that PTS exposure alters Amyloid Precursor Protein (APP) and alpha-synuclein (α-syn) metabolism in human cells of neural origin, providing a possible connection between exposure and neurodegeneration. This investigation aimed to reveal, in vitro in human non-neural cells (HEK293), the aftermath of the same exposure on the processing of APP and α-syn. Data presented here, indicate changes in APP metabolism, acquisition of different cellular topologies of the newly generated APP fragments, changes in monomeric α-syn accumulation and multimerization, indicating that APP and α-syn processing is possibly altered in the periphery by EMR. These effects are accompanied by a substantial increase in the levels of Reactive Oxygen Species (ROS). Further investigation is required in order to provide insights into the interaction of PTS with non-neural cells affecting the peripheral systemic functional stability. This is necessary because nowadays whole body human exposure from various EMR sources is a fact in normal life with the valid estimation that they may be increased in view of the forthcoming 5G telecommunications network implementation.

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentration over a prolonged time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked oxidative damage and inflammation as evident by the reduction in the super oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured spinal cord tissue, as well as, the significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α). Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of the above mentioned biochemical parameters and shifted them toward the control group values. Genistein induced an increase in the activity of SOD and the level of IL-10, while causing a decrease in the levels of NO, MDA and TNF-α in injured spinal cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for treating inflammatory nervous tissue conditions, especially when combined as an implantable drug-delivery system.

In this work α-synuclein amyloid fibrils, formation of which is a biomarker of the Parkinson’s disease, were investigated with the use of fluorescent probe thioflavin T (ThT). Experimental conditions of the protein fibrillogenesis were chosen so that a sufficient number of continuous measurements can be performed to characterize and analyze all stages of this process. The reproducibility of fibrillogenesis and the structure of the obtained aggregates (that is a critical point for their further investigation) were proved using a wide range of physical-chemical methods. For determination of ThT—α-synuclein amyloid fibrils binding parameters sample and reference solutions were prepared with the use of equilibrium microdialysis. By absorption spectroscopy of these solutions ThT—fibrils binding mode with the binding constant about 10⁴ M⁻¹ and stoichiometry of ThT per protein molecule about 1:8 was observed. Fluorescence spectroscopy of the same solutions with the subsequent correction of the recorded fluorescence intensity on the primary inner filter effect allowed to determine another mode of ThT binding to fibrils with the binding constant about 10⁶ M⁻¹ and stoichiometry about 1:2500. Analysis of photophysical characteristics of the dye molecules bound to the sites of different binding modes allowed to assume the possible localization of these sites. Obtained differences in the ThT binding parameters to amyloid fibrils formed from α-synuclein and other amyloidogenic proteins, as well as in the photophysical characteristics of the bound dye, confirmed the hypothesis of amyloid fibrils polymorphism.

We propose and experimentally realize a scheme of the optical nonreciprocity (ONR) using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition Fg=4→Fe=3, we first study the cavity-transmission property in different coupling field, and verify that within the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) shows ONR. Qualitative theoretical analysis shows that the stable ground-state Zeeman coherence is necessary for intracavity EIT. However, due to the frequency degeneracy, the large Rabi frequency of counter-propagating coupling field can reduce the number of effective atoms and weaken the strong-coupling of the atom-cavity, which determines that ONR based on intracavity EIT occurs only at weaker probe intensity. Furthermore, the ONR transmission with high contrast, linewidth-narrowed and broadband is experimentally demonstrated.

The idea of strong and weak adjacencies between vertices has been generalized into fuzzy graphs and intuitionistic fuzzy graphs (IFGs) and it is an important part of making decisions. However, one or two membership degrees are not always sufficient for making decisions on real-world problems that need an answer of types “yes, neutral, and no". Consequently, in previous work, we generalized the concept into picture fuzzy graphs (PFGs) where each element in the PFG has membership, neutral, and non-membership degrees. Moreover, we constructed the notion of the coloring of PFGs based on strong and weak adjacencies between vertices. In this paper, we investigate some properties of the chromatic number of PFGs based on the concept of strong and weak adjacencies between vertices. According to the properties, we construct an algorithm to find the chromatic number of PFGs. The algorithm is usefull when we work with large PFGs. Further, we improve the method to implement the PFG’s coloring for determining traffic signal phasing at an intersection. A case study has also been done to evaluate the method.

In this work we report recent theoretical calculations of a superconducting island in a strong vortex confinement regime. The obtained results reveal the evolution of superconducting condensate as a function of electron mean-free path (l) with the evolution of an applied magnetic field H0. The results of this study provide an insight about the emergent superconducting properties under such conditions, using the Ginzburg-Landau numerical simulations where spatial variation of thickness d on island, omnipresent in these kind of structures grown on Si (111), is taken into account. These results offer a new route to tailor superconducting circuits by using the controlled bombardment, in order to explore the impact on vortex distribution, phase of order parameter, number of vortices, free energy and the first H1 and second critical field H2.

We present simple relations for nuclear stability and nuclear binding energy with respect to three gravitational constants associated with electroweak, strong and electromagnetic interactions.

Natural Gas (NG) processing is a prominent industrial separation process. Among the available techniques, the innovative membrane process shows potential for efficient removal of impurities, including carbon dioxide (CO₂). This study focuses on utilizing breakthroughs in membrane separation to drive sustainable CO₂ extraction from natural gas. Through comprehensive research and analysis, we explore the effectiveness and feasibility of membrane-based systems in removing CO₂ impurities from NG, thus promoting greener and more sustainable industrial practices. Our findings underscore the transformative nature of membrane separation technology, presenting new possibilities for a more environmentally-friendly and sustainable approach to CO₂ extraction from natural gas.Natural Gas (NG) processing utilizes various techniques for impurity removal, with the membrane process emerging as a promising option for efficient carbon dioxide (CO₂) extraction. This research proposes the integration of a simple mathematical model into ASPEN HYSYS to design a membrane system for CO₂/CH₄ separation. The study also investigates parameter sensitivities by altering operating conditions, such as feed composition and pressure, as well as membrane properties, including selectivity. By analyzing these variables, we aim to optimize the performance and efficiency of the membrane system, facilitating the sustainable extraction of CO₂ from NG. The findings contribute to advancing the design and operation of membrane-based processes for CO₂ separation, paving the way for greener and more sustainable industrial practices. In addition, this study explores various configurations for optimizing the design of the membrane system, including single-stage with and without recycling as well as double-stage configurations. The investigation demonstrates that methane recovery can be enhanced through the recycling of the permeate stream and by implementing a double stage membrane system. These findings highlight the potential for improving the efficiency and performance of the membrane system, enabling higher methane recovery rates. By considering different configurations, this research contributes to the development of more effective and sustainable CO₂ extraction processes from natural gas.

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans is still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple of the risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.

Malignant melanoma is one of the most aggressive and resistant tumor types which is often accompanied by poor prognosis when spread to nearby or distant tissues. Even though an increasing number of second-line therapies are available for cancer patients, the 5-year survival rate of melanoma patients with regional and distant metastases is still rather low. Therefore, there is an urgent need to develop new, highly efficient treatments. Melanocortin-1-receptor (MC1R) is a cell surface receptor for α-MSH. It is responsible for melanogenesis and is shown to be overexpressed on the surface of cancer cells in a subset of melanoma patients. Here, we designed and synthesized α-MSH analogs and conjugated them to daunomycin through oxime linkage. Using our peptide-drug conjugates (Dau-α-MSHs), we performed comparative in vitro and in vivo evaluations to reveal their suitability for tumor targeting. Firstly, the expression level of MC1R was determined in various melanoma cell lines via RT-qPCR. Then, we examined the antiproliferative effect of our Dau-α-MSHs, moreover we determined the cellular uptake profile and intracellular localization of Dau-α-MSHs. The most efficient Dau-α-MSHs were investigated in vivo using a murine xenograft melanoma model. We found that various cell lines show differential expression on the mRNA levels. We also showed that healthy primary cells have lower expression of MC1R compared to tumor cell lines. Moreover, the concentration-dependent cellular uptake profile of Dau-α-MSHs was detected and the compounds exhibited a great antiproliferative effect on melanoma cell lines. We also provided evidence that our novel Dau-α-MSHs can inhibit tumor expansion significantly and are suitable for targeted tumor therapy.

Many biological functions of curcumin have been reported. As certain bioactivities of curcumin are eliminated by antioxidants, reactive oxygen species generated by curcumin have been suggested as a relevant mechanism. In the present study, effects of different types of antioxidants on stability and bioactivities of curcumin were analyzed. High concentrations (>4mM) of the thiol antioxidants including N-acetylcysteine (NAC), glutathione (GSH) and β-mercaptoethanol accelerated decomposition of curcumin and other curcuminoids; Submillimolar levels (<0.5 mM) of GSH and NAC rather improved their stability. Ascorbic acid or superoxide dismutase also stabilized curcumin regardless of their concentration. Cellular levels and bioactivities of curcumin including cytotoxicity and induction of heme oxygenase-1 were significantly reduced in the presence of 8 mM of GSH and NAC. The effects were enhanced in the presence of submillilmolar GSH and NAC, or non-thiol antioxidants. The present results indicate that antioxidants with reduced thiol group could directly interact with α, β-unsaturated carbonyl moiety of curcuminoids and modulate their stability and bioactivity.

In this work epitaxial Au islands have been grown on epitaxial α-Fe2O3 thin film by pulsed laser deposition on SrTiO3(111) substrate. Both Au and α-Fe2O3 layer show an island-type growth with an average particle size of 40 and 62 nm, respectively. The crystallographic coupling of lattices is confirmed with a rotation of 30º between the in-plane crystallographic axes of α-Fe2O3(0001) structure and those of SrTiO3(111) substrate and between the in-plane crystallographic axes of Au(111) and those of α-Fe2O3(0001) structure. α-Fe2O3 is the only phase of iron oxide identified before and after its functionalization with Au nanoparticles. In addition, its structural character-istics are also preserved after Au deposition, with minor changes at short-range order. The func-tional character of the complex systems as gas sensor has been proven at room temperature. Con-ductance measurements of Au(111)/α-Fe2O3(0001)/ SrTiO3(111) system show that the incorpora-tion of Au islands on top of the α-Fe2O3(0001) layer induces an enhancement of the gas-sensing ac-tivity for CO and CH4 gas in comparison to a bare α-Fe2O3(0001) layer grown on SrTiO3(111).

Abstract: Oncogenic RAS mutations drive more than half of human cancers, and RAS inhibition is the holy grail of oncology. Thirty years of relentless efforts and harsh disappointments have taught us about the intricacies of oncogenic RAS signalling that allow us to now get a pharmacological grip on this elusive protein. The inhibition of effector pathways, such as the RAF-MEK-ERK pathway, has largely proven disappointing. So far, most of these efforts were aimed at blocking the activation of ERK. Here, we discuss RAF dependent pathways that are regulated through RAF functions independent of catalytic activity and their potential role as targets to block oncogenic RAS signalling. We focus on the now well documented roles of RAF kinase independent functions in apoptosis, cell cycle progression and cell migration.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.

The seeds of cultivated peanut, Arachis hypogaea, are an agronomically important crop produced for human nutrition, oilseed and feed stock. Peanut seed is the single most expensive variable input cost and thus producers require seed with excellence performance in terms of germination efficiency. During the maturation process, triglycerides are stored in oil bodies as an energy resource during germination and seedling development. The stability of oil body membranes is essential for nutrient mobilization during germination. This study focused on evaluating the phytosterol composition in seed components including the kernel, embryo (heart), and seed coat or skin. Samples of different maturity classes were analyzed for macronutrient and phytosterol content. The three most abundant phytosterols, β-sitosterol, campesterol, and stigmasterol, comprised 82.29%, 86.39%, and 94.25% of seed hearts, kernels, and seed coats, respectively. Stigmasterol concentration was highest in the seed kernel providing an excellent source of this sterol known to have beneficial effects on human health. Peanut hearts contained the highest concentration of sterols by mass potentially providing protection and resources for the developing seedling. The amount of α-tocopherol increases in peanut hearts during the maturation process providing protection from temperature stress and stability required for seedling vigor. These results suggest that phytosterols may play a significant role in the performance of seeds and provides a possible explanation for the poor germination efficiency of immature seeds.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

In recent years, wireless power transfer (WPT) has progressed rapidly in both theory and commercialization abroad. However, existing research into WPT coil design for low-power devices is limited. This paper investigates coil structure using printed circuit board (PCB) for magnetic resonant coupling WPT to address this gap. Specifically, the impacts of key geometric parameters on the coil quality factor and coupling coefficient are analysed through models and simulations. Equivalent PCB coils were formed for mutual inductance models, and four basic compensation circuits were analysed. The impacts of changes in coil thickness, line width, turn spacing, and number of turns on the quality factor of PCB coils were analysed with a fixed outer diameter of the coil. In this paper, to mitigate the coil offset while retaining PCB manufacturing simplicity for practical uses, a dual layer PCB coil structure is proposed. The structure optimizated PCB coil could offer remarkable improvements in the WPT system for low power electronic devices.

The development of integrated, compact, and multifunctional photonic circuits is crucial to increase the capacity of all-optical signal processing for communications, data management or microsystems. Plasmonics brings compactness to numerous photonic functions, but its integration into circuits in not straightforward due to insertion losses and poor modes matching. The purpose of this article is to detail the integration strategies of plasmonic structures on dielectric waveguides, and to show through some examples the variety and the application prospect of integrated plasmonic functions.

Ship pilots and maritime safety administration have an urgent need for more accurate and earlier warnings on strong wind gusts. This study firstly investigates the “Oriental Star” cruise ship cap-sizing event in 2015, one of the deadliest shipwreck events in recent years, and explores all related hydro-meteorological components in a global mesoscale model. It is found that, rather than the missing signal in raw surface wind prediction, the cumulus precipitation variable (CP) increases dramatically during the accident occurrence, which significantly corresponds to the sub-grid strong wind gust. The effective lead-time can be extended from 24hr (deterministic model) to 48hr (en-semble model). This finding is then verified in another two recent deadly cruise boat accidents. The introduction of the new variable is bearing the hope of improvement to the current maritime safeguard system, on predicting sub-grid strong wind gusts for small-size cruise boats in offshore and inland rivers. Finally, an automatic-response system is developed to provide economical con-vection prediction via Inmarsat email communication, aiming to explore operational severe con-vective gust early-warning and appropriate numerical mesoscale model application.

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

We report the strong coupling between plasmonic surface lattice resonances (SLRs) and photonic Fabry-Pérot (F-P) resonances in a microcavity embedded with two-dimensional periodic array of metal-insulator-metal nanopillars. For such a plasmonic-photonic system, we show that the SLR can be strongly coupled to the F-P resonances of both the odd- and even orders, and that the splitting energy reaches as high as 138 meV in the visible regime. We expect that this work will provide a new scheme for strong coupling between plasmonic and photonic modes.

The presence of valuable bioactive compounds in European eel (Anguilla anguilla) skin was studied. For it, proximate and lipid class compositions and analysis of the fatty acid (FA) profile (individual FAs; FA groups, i.e., saturated, monounsaturated, and polyunsaturated; FA ratios, i.e., polyunsaturated/saturated, ω3/ω6) were determined and compared to the composition of the eel muscle. As a result, higher (p&lt;0.05) levels of proteins (271.6 g·kg-1), lipids (38.0 g·kg-1), ash (27.7 g·kg-1) and ω6 FAs were observed in the skin tissue. Contrary, the muscle tissue showed higher (p&lt;0.05) moisture, ω3 FA and ω3/ω6 values. Regarding lipid classes, a higher (p&lt;0.05) proportion of phospholipids (111.1 g·kg-1 lipids), sterols (104.7 g·kg-1 lipids), α-tocopherol (274.0 mg·kg-1 lipids), and free fatty acids (43.6 g·kg-1 lipids) was observed in the skin tissue. No differences (p&gt;0.05) between both tissues could be detected for triacylglycerol and FA group (saturated, monounsaturated, and polyunsaturated) values, as well as for the polyunsaturated/saturated ratio. It is concluded that eel skin, a by-product resulting from commercial processing, can be considered a valuable source to provide the food and pharmaceutical industries with useful value-added constituents such as proteins, lipids, ω3 FAs, phospholipids, and α-tocopherol.

In this study, we aimed to reveal the proinflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabe-tes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy partici-pants. Levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleu-kin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) were measured in the serum of the par-ticipants. The ANOVA Bonferonni and Kruskal Wallis Dunn tests were used for the comparison of the inflammation markers and vitamin D levels between the groups. Upon covariance analy-sis with age, gender and BMI; Vit D levels of T2DM group were found to be significantly lower (p<0.003). Proinflammatory markers and CRP were found to be significantly higher in predia-betic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the proinflammatory effects of Vit D on the initiation of inflammation in both prediabetes and diabetes mellitus.

Oxidative stress-mediated damage is often a downstream result of Parkinson’s disease (PD), which is marked by sharp decline in dopaminergic neurons within the nigrostriatal regions of the brain, accounting for the symptomatic motor deficits in patients. Regulating the level of oxidative stress may present a beneficial approach in preventing PD pathology. Here, we assessed the efficacy of a nicotinamide adenine phosphate (NADPH) oxidase (NOX) inhibitor, an exogenous reactive oxygen species (ROS) regulator synthesized by Aptabio therapeutics with the specificity to NOX-1, 2, and 4. Utilizing N27 rat dopaminergic cells and C57Bl/6 mice, we confirmed that the exposures of alpha-synuclein preformed fibrils (PFF) induced protein aggregation, a hallmark in PD pathology. In vitro assessment of the novel compound revealed an increase in cell viability and decreases in cytotoxicity, ROS, and protein aggregation (Thioflavin-T stain) against PFF exposure at the optimal concentration of 10nM. Concomitantly, the oral treatment alleviated motor deficits in behavioral tests, such as hindlimb clasping, rotarod, pole, nesting, and grooming test, via reducing protein aggregation, based on rescued dopaminergic neuronal loss. The suppression of NOX-1, 2, and 4 within the striatum and ventral midbrain regions including SNc contributed to neuroprotective/recovery effects, making it a potential therapeutic option for PD.

With our long experience in the field of unification of gravity and quantum mechanics, we understood that, when mass of any elementary is extremely small/negligible compared to macroscopic bodies, highly curved microscopic space-time can be addressed with large gravitational constants and magnitude of elementary gravitational constant seems to increase with decreasing mass and increasing interaction range. In our earlier publications, we proposed that, 1) There exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions; 2) There exists a strong interaction elementary charge in such a way that, it's squared ratio with normal elementary charge is close to inverse of the strong coupling constant; and 3) Considering a fermion-boson mass ratio of 2.27, quarks can be split into quark fermions and quark bosons. Further, we noticed that, electroweak field seems to be operated by a primordial massive fermion of rest energy 584.725 GeV and hadron masses seem to be generated by a new hadronic fermion of rest energy 103.4 GeV. In this context, starting from lepton rest masses to stellar masses, we have developed many interesting and workable relations. With further study, a workable model of final unification can be developed.

Here we evaluate the chemistry of mineral soil solutions collected by suction lysimeters in a small mountain catchment that was affected by acidification-related spruce die-back. The aim was to obtain new insights into spatial patterns of nutrient partitioning during acidification recovery. This was achieved by comparing nutrient concentrations in soil solutions, collected along a V-shaped valley, with those in runoff. Five nests of suction lysimeters were installed in the 33-ha UDL catchment at different topographic positions (hilltops, slopes and valley). Following a 1-year equilibration, monthly samples of soil solutions were collected over a 2-year period. In the vicinity of each lysimeter nest, soil pits were excavated for a study of soil chemistry. Soil solutions were analyzed for SO42-, NO3-, DOC, NH4+, Na+, K+, Ca2+, Mg2+, and total dissolved Al concentrations, DOC and pH. For a P release estimation, ammonium oxalate extraction of soil samples was performed. Comparison of soil water data from this study with other European studies indicated that major environmentally relevant chemical species at UDL had concentrations similar to median concentrations across numerous previously acidified sites. CEC (≤ 58 meq kg-1) and BS (≤ 13 %), however, were significantly lower at UDL than at other European sites, documenting incomplete recovery from acidification. Spatial trends and seasonality in soil water chemistry support belowground inputs from mineral-stabilized legacy pollutants and soil nutrients. Seasonal variability of soil water sulfate and nitrate was significant. High nitrate in soil solutions during summer originated during the preceding dormant season, and high sulfate concentrations observed during the winter originating from recycled organic S during the summer. Higher concentrations of SO42-, NO3-, and base cations in runoff than in soil solutions may be explained by lateral surficial runoff leaching pollutants and nutrients from very shallow soil horizons. Nearly 30 years after peak acidification, solutions in mineral subsoil at UDL exhibited similar concentrations of SO42-, Ca2+ and Mg2+ as median values at the Pan-European International Co-operative Program (ICP) Forest sites, yet NO3- concentrations were an order of magnitude higher than the ICP sites. Calcium applied on soil surface by liming 32 to 11 years ago affected runoff more than soil solutions, suggesting contribution of both shallow soil water and groundwater to runoff.

In this paper, a kind of single-walled carbon nanotube nonlinear model is developed, and the strongly nonlinear dynamic characteristics of such carbon nanotubes subjected to random magnetic field are studied. The nonlocal effect of microstructure is considered based on the theory of nonlocal elasticity. The natural frequency of the strongly nonlinear dynamic system is obtained by the energy function method, the drift coefficient and the diffusion coefficient are verified. The stationary probability density function of the system dynamic response is given and the fractal boundary of the safe basin is provided. Theoretical analysis and numerical simulation show that stochastic resonance occurs when varying the random magnetic field intensity. The boundary of safe basin has fractal characteristics and the area of safe basin decreases when the intensity of the magnetic field permeability increases.

An array of diverse processes and factors have been linked to the pathoetiology and pathophysiology of Parkinson’s disease (PD), including systemic CNS factors. This article reviews some of the many processes and factors linked to the emergence and progression of PD that culminates in the loss of substantia nigra pars compacts (SNpc) in PD patients. It is proposed that SNpc astrocytes may be a key hub, with numerous systemic and CNS factors acting to suppress the astrocyte tryptophan-melatonin pathway, leading to a loss of astrocyte melatonin and lactate for SNpc dopamine neurons. Consequently, dopamine neurons show an increase in α-synuclein, oxidative stress and suboptimal mitochondrial function, partly due to the loss of melatonin induced PTEN-associated kinase (PINK)1/parkin and mitophagy. This leads to an increase in the major histocompatibility (MHC)-1 and the chemoattraction of CD8+ T cells that destroy SNpc dopamine neurons in an ‘autoimmune’/’immune-mediated’ manner. The upstream processes driving the end-point ‘chaos’ of SNpc dopamine neuron loss are proposed to be driven by the suppression of night-time pineal melatonin, gut microbiome derived butyrate and possibly bcl2-associated athanogene (BAG)-1, which all act to suppress the glucocorticoid receptor (GR) translocation to the nucleus in all systemic and CNS cells, thereby potentiating the effects of the rising levels of cortisol over the night and accelerated rise in the course of the cortisol awakening response (CAR). The potentiation of cortisol effects at the GR has consequences for the homeostatic regulation of the diverse array of systemic and CNS microenvironments, as well as a distinct regulation of different immune and glia cells. The morning CAR is classically proposed to ‘prepare the body for the coming day’. However, the differential regulation of the GR over the circadian rhythm at night would indicate that such preparation for the coming day may be powerfully determined by night-time factors and processes. The article integrates this systemic, night-time pathoetiology with the ‘immune-mediated’ processes that ultimately drive SNpc dopamine neuron loss. This has a number of novel future research and treatment implications.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

Beef meat production in Uruguay is based on pasture or concentrate feeding systems, leading to differences in meat quality. The objective of this study was to compare the oxidative and color stability during refrigerated retail display of beef meat from these two systems. For this, ten Aberdeen Angus steers were reared and fed on pasture and other ten were finished on a concentrate diet. After slaughter, the Semimembranosus muscle was cut into slices and put in a refrigerated showcase for 3, 6, and 9 days simulating commercial conditions. The β-carotene, α-tocopherol, and fatty acid content were determined before the display, and the lipid and protein oxidation, color parameters, and heme iron content were determined before and during the display. Meat from steers fed pasture had a lower content of intramuscular fat, monounsaturated fatty acids, n-6/n-3 ratio, lipid and protein oxidation, L* and a* values, and a higher content of linolenic acid, DHA, total n-3, β-carotene, and α-tocopherol. In conclusion, meat from pasture-fed steers was more stable during the retail display, which can probably be explained by a higher content of antioxidant compounds, such as β-carotene and α-tocopherol, and presented a healthier fatty acid profile.

To enhance the mechanical properties (i.e. strength and elongation) of the face-centered cubic (fcc) α-phase in the Au-Cu-Al system, this study focused on the introduction of the martensite phase (doubled B19 (DB19) crystal structure of Au2CuAl) via the manipulation of alloy compositions. Fundamental evaluations, such as microstructure observations, phase identifications, thermal analysis, tensile behavior examinations, and reflectance analysis have been conducted. The presence of fcc annealing twins was both observed in the optical microscope (OM) and the scanning electron microscope (SEM) images. Both the strength and elongation of the alloys were greatly promoted while the DB19 martensite phase was introduced into the alloys. Amongst all the prepared specimens, the 47Au41Cu12Al and the 44Au44Cu12Al alloys performed the optimized mechanical properties. The enhancement of strength and ductility in these 2 alloys was achieved while the stress plateau was observed during the tensile deformation. A plot of the ultimate tensile strength (UTS) against fracture strain was constructed to illustrate the effects of the introduction of the DB19 martensite phase on the mechanical properties of the alloys. Regardless of the manipulation of the alloy compositions and the introduction of the DB19 martensite phase, the reflectance stayed almost identical to pure Au.

We report the results of our study of approved drugs as potential treatments for COVID 19, based on the application of various bioinformatics predictive methods. The drugs studied include chloroquine, ivermectin, remdesivir, sofosbuvir, boceprevir, and α-difluoromethylornithine (DMFO). Our results indicate that these small molecules selectively bind to stable, kinetically active residues and residues adjoining them on the surface of proteins and inside protein pockets, and that some prefer hydrophobic over other active sites. Our approach is not restricted to viruses and can facilitate rational drug design, as well as improve our understanding of molecular interactions, in general.

The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

Metal nanoparticles supporting plasmons are widely used to enhance electromagnetic fields, resulting in strong light-matter interactions at the nanoscale in a diverse range of applications. Recently, it has been shown that when metal nanorods are periodically arranged with proper lattice periods, surface lattice resonances (SLRs) can be excited and near fields can be greatly enhanced over extended volumes. In this work, we report significant near field enhancement over even larger volumes by placing the metal nanorod array within a Fabry-Pérot (F-P) microcavity. Results show that taking advantage of strong coupling between the SLR and the photonic F-P resonances, the electric field intensity of the bonding split mode can be enhanced by up to 1935 times, which is about three times of the enhancement of the SLR, and the greatly enhanced field can extend over most of the F-P microcavity. We further show that the F-P resonances of both odd and even orders can strongly couple to the SLR by varying the nanorods position from the middle of the microcavity. We expect that the proposed plasmonic-photonic coupling system will find promising applications in nanolasers, nonlinear optics and sensing.

In this paper, we introduce a new iteration scheme, named as the S**-iteration scheme, for approximation of fixed point of the nonexpansive mappings. This scheme is faster than Picard, Mann, Ishikawa, Noor, Agarwal, Abbas, Thakur, and Ullah iteration schemes. We show the stability of our instigated scheme and give a numerical example to vindicate our claim. We also put forward some weak and strong convergence theorems for Suzuki's generalized nonexpansive mappings in the setting of uniformly convex Banach spaces. Our results comprehend, improve, and consolidate many results in the existing literature.

At nuclear scale, we present three heuristic relations pertaining to strong and electroweak coupling constants. With these relations, close to beta stability line, it is possible to study nuclear binding energy with a single energy coefficient of magnitude $\left(\frac{1}{{\alpha }_s}\right)\left[\frac{e^2}{4\pi {\epsilon }_0{R}_0}\right]\approx 10.0\text{MeV}\text{.}$ With reference to up and down quark masses, it is also possible to interpret that, nuclear binding energy is proportional to the mean mass of $\left[\left(2m_u+m_d\right)\text{and}\left(m_u+2m_d\right)\right]\approx 10.0\text{MeV}.$

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

Background: Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here we report studies that address this question. Methods: 14 weeks on high-fat diet (HFD) with high sucrose, C57BL/6 mice revealed a phenotype of liver steatosis. Transcriptional profiling analysis of the liver tissues was performed using RNA sequencing (RNA-seq). Results: Our RNA-seq data revealed 692 differentially expressed genes involved in processes of lipid metabolism, oxidative stress, immune responses, and cell proliferation. Notably, the gene encoding neutral sphingomyelinase SMPD3, was predominantly upregulated in the liver tissues of the mice displaying a phenotype of steatosis. Moreover, nSMase2 activity was elevated in these tissues of the liver. Pharmacological and genetic inhibition of nSMase2 prevented intracellular lipid accumulation and TNFα-induced inflammation in in-vitro HepG2-steatosis cellular model. Furthermore, nSMase2 inhibition ameliorates oxidative damage by rescuing PPARα and prevent cell death associated with high glucose/oleic acid-induced fat accumulation in HepG2 cells. Conclusions: Collectively, our findings highlight the prominent role of nSMase2 in hepatic steatosis which could serve as a potential therapeutic target for NAFLD and other hepatic steatosis-linked disorders.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress was determined by qRT-PCR, TNF-α protein by ELISA, ROS by DCFH-DA assay, HIF-1α/p38/ERK-1,2/NF-κB phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed by qRT-PCR/IHC and plasma TNF-α/hs-CRP/MDA/OX-LDL by ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CHOP, ATF6, SOD2, and NRF2 expression (P≤0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α/p38/NF-κB phosphorylation, while MAPK/NF-κB inhibitors and antioxidants/ROS scavengers attenuated TNF-α production (P≤0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (P≤0.05). Our findings support a cooperative interaction between metabolic and ER stresses, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also shows the therapeutic potential of ROS scavengers/anti-oxidants in inflammatory conditions involving metabolic/ER stresses.

Chlorotoxin (CTX) is a 36–amino acid peptide with 8 Cys residues that forms four Cys-Cys bonds. It has high affinity for the glioma-specific chloride channel and matrix metalloprotease-2. Structural and binding properties of CTX analogs with various Cys residue substitutions with L-a-aminobutyric acid (Abu) have been previously reported. Using 4.2 ìs molecular dynamics, we compared the conformational and essential space sampling of CTX and analogs [Abu/Ser^2,19]CTX, [Abu/Ser^5,28]CTX, [Abu/Ser^16,33]CTX, [Abu/Ser^20,35]CTX, and [Abu/Ser^{2,5,16,19,20,28,33,35}]CTX. The native and substituted peptides maintained a high degree of a-helix propensity from residues 8 through 21, with the exception of [Ser^5,28]CTX and [Abu^16,33]CTX. In agreement with previous circular dichroism spectropolarimetry results, the C-terminal b-sheet content varied less from residues 25 through 29 and 32 through 36 and was well conserved in all analogs, except: [Abu^16,33]CTX, [Ser^20,35]CTX, [Abu^{2,5,16,19,20,28,33,35}]CTX, and [Ser^{2,5,16,19,20,28,33,35}]CTX. The Cys¹⁶-Cys³³ and Cys²⁰-Cys³⁵ Cys-Cys bonds appear to be required to maintain the ab-motif of CTX. Their selective substitution with Ser^16,33 however, may mitigate the destabilizing effect of Cys¹⁶-Cys³³ substitution by the formation of an inter residue H-bond from OgH of Ser¹⁶ to OgH of Ser³³ bridged by a water molecule. All peptides shared considerable sampled conformational space, which explains the retained receptor binding of the nonnative analogs.

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

Highly-correlated electrons – electrons that engage in strong electron-electron interactions – have been observed in transition metal oxides and quantum dots and can create unusual material behavior that is difficult to model, such as switching between a low resistance metal state and a high resistance Mott insulator state. Tests of devices using a layer-by-layer deposition process for forming multilayer arrays of ferritin (a transition metal (iron) oxide storage protein) have been previously reported that indicate that highly-correlated electron transport is occurring, consistent with models of electron transport in quantum dots. This paper reports the results of the effect of various degrees of structural homogeneity on the electrical characteristics of these ferritin arrays, as well as demonstrating that these structures can provide a switching function associated with the circuit that they are contained within, consistent with the observed behavior of highly-correlated electrons.

As there exist no repulsive forces in strong interaction, in a hypothetical approach, strong interaction can be assumed to be equivalent to a large gravitational coupling. Based on this concept, strong coupling constant can be defined as a ratio of the electromagnetic force and the gravitational force associated with proton, neutron, up quark and down quark. With respect to the product of strong coupling constant and fine structure ratio, we review our recently proposed two semi empirical relations and coefficients 0.00189 and 0.00642 connected with nuclear stability and binding energy. We wish to emphasize that- by classifying nucleons as ‘free nucleons’ and ‘active nucleons’, nuclear binding energy can be fitted with a new class of ‘three term’ formula having one unique energy coefficient. Based on the geometry and quantum nature, currently believed harmonic oscillator and spin orbit magic numbers can be considered as the lower and upper “mass limits” of quark clusters.

The Ayers Rock of Australia which is known for its charming colors at different time is actually the Celestial Body Ring of the planet Earth that implies the great Celestial Body Love happened on Earth long long ago. The Tasmania island of Australia which is known for the World Heart is actually in the state of face to face with the main island of Australia, which implies the image spokesperson for the inner core (the heart) of the planet Earth. In other words, with the outline of the main island of Australia, the basic key information of the inner core of the planet Earth could be easily obtained by deducing logically, just like the similarity between the fists and heart of human body. Similar to the mechanism of the blood circulation dominated by the heart of human body, it is dominated and motivated by the inner core of the Earth which forms the circulation of mantle magma between the crust and the inner core, and what leads to the formation of expanding and active area on the equatorial and middle-lower latitude area and the silent and convergent area on the North and South Pole central area. Therefore, the mantle magma whirlpools under the crust on the North and South Pole are supposed to exist logically. The walking sideways of the crabs just implies the celestial body language of the motive trend of the main island of Australia based on their similar outline.

With reference to electromagnetic interaction and Abdus Salam’s strong (nuclear) gravity, 1) Square root of ‘reciprocal’ of the strong coupling constant can be considered as the strength of nuclear elementary charge. 2) ‘Reciprocal’ of the strong coupling constant can be considered as the maximum strength of nuclear binding energy. 3) In deuteron, strength of nuclear binding energy is around unity and there exists no strong interaction in between neutron and proton. $G_s\cong 3.32688\times {10}^{28}{\mathrm{m}}^3{\mathrm{kg}}^{-1}{\sec }^{-2}$ being the nuclear gravitational constant, nuclear charge radius can be shown to be, $R_0\cong \frac{2G_s{m}_p}{c^2}\cong 1.24\mathrm{fm}.$ $e_s\cong \left(\frac{G_s{m}_p^2}{\hslash c}\right)e\cong 4.716785\times {10}^{-19}\mathrm{C}$ being the nuclear elementary charge, proton magnetic moment can be shown to be, ${\mu }_p\cong \frac{e_s\hslash }{2m_p}\cong \frac{e{G}_s{m}_p}{2c}\cong 1.48694\times {10}^{-26}\mathrm{J}{.\mathrm{T}}^{-1}.$ ${\alpha }_s\cong {\left(\frac{\hslash c}{G_s{m}_p^2}\right)}^2\cong 0.1153795$ being the strong coupling constant, strong interaction range can be shown to be proportional to $\exp \left(\frac{1}{{\alpha }_s^2}\right).$ Interesting points to be noted are: An increase in the value of ${\alpha }_s$ helps in decreasing the interaction range indicating a more strongly bound nuclear system. A decrease in the value of ${\alpha }_s$ helps in increasing the interaction range indicating a more weakly bound nuclear system. From $Z\cong 30$ onwards, close to stable mass numbers, nuclear binding energy can be addressed with, ${\left(B\right)}_{A_s}\cong Z\times \left\{\left(\frac{1}{{\alpha }_s}+1\right)+\sqrt{\sqrt{30\times 31}}\right\}\left(m_n-m_p\right)c^2\approx Z\times 19.66\mathrm{MeV}.$ With further study, magnitude of the Newtonian gravitational constant can be estimated with nuclear elementary physical constants. One sample relation is, $\left(\frac{G_N}{G_s}\right)\cong \frac{1}{2}{\left(\frac{m_e}{m_p}\right)}^{10}\left[\sqrt{\frac{G_F}{\hslash c}}/\left(\frac{\hslash }{m_{e}c}\right)\right]$ where $G_N$ represents the Newtonian gravitational constant and $G_F$ represents the Fermi’s weak coupling constant. Two interesting coincidences are, ${\left(m_p/m_e\right)}^{10}\cong \exp \left(1/{\alpha }_s^2\right)$ and $2G_s{m}_e/c^2\cong \sqrt{G_F/\hslash c}.$

In this work, we explore the intrinsic disorder status of the three members of the synuclein family of proteins - α-, β-, and γ-synucleins. We also analyzed the peculiarities of the amino acid sequences and modeled 3D structures of the human synuclein family members to find potential effects of pathological mutations. Furthermore, we conducted a comparative sequence-based analysis of the synuclein proteins from various evolutionary distant species and evaluated their levels of intrinsic disorder using a set of commonly used bioinformatics tools. Next, we conducted a detailed functional disorder analysis of the proteins in the interactomes of the human synuclein family members using various web-based disorder analysis and prediction tools, such as RIDAO, D2P2 and FuzDrop. We identify that the interactome of human α-synuclein has relatively higher levels of intrinsic disorder, as compared to the interactomes of human β- and γ- synucleins. These observations highlight the critical importance of intrinsic disorder of human α-synuclein and its interactors in neuronal processes as compared to other proteins of the synuclein family.

Acetic acid bacteria (AAB) form a bacterial film on the surface of alcoholic solutions and ferment ethanol to acetic acid while also producing bioactive compounds. To discover functional AAB for industrial use, we isolated and selected strains from farm-produced vinegars using a CaCO3-containing medium. The seven strains belonged to Acetobacter cerevisiae and A. pasteurianus. Physiological properties were determined, including ethanol tolerance at up to 12% (v/v). Acidification at a growth temperature of 40 ℃ was seen for GHA 7, GYA 23, JGB 21-17, and GHA 20 strains, which may be useful in vinegar production where thermotolerant AAB are required. The seven AAB isolates had strong antibacterial activity against Staphylococcus aureus. Antioxidant activity was 2- and 4-fold higher, respectively, for A cerevisiae and A. pasteurianus than for the control, 1% acetic acid. We also observed 91.3% inhibition of angiotensin-converting enzyme activity for the KSO 5 strain, higher than that for the positive control, 0.1% captopril (76.9%). All strains showed complete inhibition of α-glucosidase, except JGB 21-17 and GHA 7 with 98.3% inhibition. Our work suggests usefulness of the strains selected as seed strains for highly efficient production of functional vinegar and illustrates identification of useful functional characteristics on a scientific basis.

The objective of this study was to analyze the epidemiological links of HIV, HCV and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15-87 years who took part in the Open Test Project. They were divided into two subgroups: general population and individuals from prisons, and questioned about multiple risk factors. Chi-Square Independence Test was used to establish correlations between the risk factors and the results of the screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug use (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with injecting drug use (the strongest association), unprotected sexual intercourse with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area.

We prove a quasi-pseudometric version of the strong Ekeland principle proved by P. Georgiev and T. Suzuki.

Aim: This study aims to analyze the evolution of co-author networks in Single-Balloon Enteroscope (SBE) research from 2000 to 2023, using data from the Web of Science (WoS) Core Collection. The objective is to provide a structural overview of researcher collaborations in this specialized field, highlighting key contributors and the impact of international cooperation. Method: I conducted a co-author network analysis on 149 SBE-related articles indexed in the WoS Core Collection between 2000 and 2023. Using Python (Version 3.10.5) within the PyCharm development environment (Software Version 2022.1.3), I assessed macro-level indicators including network density, clustering coefficient, number of components, and average distance. Micro-level indicators such as degree centrality, closeness centrality, and betweenness centrality were also evaluated to understand the roles of individual researchers in the network.Result: The analysis revealed that the co-author networks in SBE research have evolved over the studied period, with varying degrees of connectivity and collaboration. From 2000 to 2009, the network showed moderate clustering but high fragmentation, with a few key researchers like Nista, Enrico C., and Spada, Cristiano playing central roles. In the 2010-2019 period, network density decreased, indicating expansion in the author pool but less frequent co-authorships. However, the clustering coefficient remained high, suggesting localized collaboration. Central figures such as Itoi, Takao emerged as influential in bridging network gaps. In the most recent period (2020-2023), network density moderately increased, reflecting improved collaboration. Key contributors included Tanisaka, Yuki, and Ryozawa, Shomei, who enhanced connectivity within the network. Despite these advancements, the network remained fragmented with isolated components throughout all periods. Conclusion: The co-author networks in SBE research have shown an overall increase in collaboration over the past two decades, with key contributors playing pivotal roles in connecting disparate groups. However, the persistent fragmentation suggests a need for more integrated efforts to enhance international collaboration. Understanding these network dynamics can inform future strategies for fostering global cooperation and advancing SBE research.

We address weighted composition operators ψCφ from α-Bloch spaces to Bers-type spaces of bounded holomorphic functions on Y, where Y is a generalized Hua domain of the first kind, and obtain some necessary and sufficient conditions for the boundedness and compactness of those operators.

A Multicomponent Reaction (MCR) strategy, alternative to the known cycloaddition reaction, towards variously substituted 1-amino-1H-imidazole-2(3H)-thione derivatives has been successfully developed. The novel approach involves α-halohydrazones whose azidation process followed by tandem Staudinger/aza-Wittig reaction with CS₂ in a sequential MCR regioselectively leads to the target compounds avoiding the formation of the regioisomer iminothiazoline heterocycle. The approach can be applied to a range of differently substituted α-halohydrazones bearing also electron-withdrawing groups confirming the wide scope and the substituent tolerance of the process for the synthesis of the target compounds. Interestingly, the concurrent presence of reactive functionalities in the scaffolds so obtained, ensures postmodifications in view of N-bridgedheaded heterobicyclic structures.

A Berry geometrical phase is identified in a strongly metastable system containing dynamically responsive clathrate hydrate structures within a crystal-fluid material. High energy degeneracy in the associated chemistry produces local stability and false vacuum conditions that lead to non-extensive and non-additive contributions in the fundamental thermodynamic relation. Application of Ginzburg-Landau theory and the scaling laws reveals a coherence length and a penetration depth for a macro-scale dual superconductor. The coherence length determines non-extensive volume changes whilst its inverse gives the Higgs mass. The penetration depth determines the extent of QCD vacuum suppression whilst its inverse gives the vector boson mass together with indirect manifestation as non-additive hyperbolic curvature. Simultaneous emergence of the Ginzburg-Landau superconducting phase transition is consistent with gauge-invariant coupling of the scalar field to the Yang-Mills action in QCD. The discovery of an energy gap in the gradient energy term of the system Lagrangian is associated with a critical correlation length revealed in the transition from a gapped to a gapless superconducting state. Together with the emergence and absorption of the Higgs-like scalar field, a mechanism for describing a renormalized QCD mass gap arises.

In this article, many experimental similarities between electromagnetic fields (which are applied in systems of electrons, atoms, and liquids) and strong interaction fields (which are applied in systems of quarks, nucleons, and nuclei) are reviewed. The currently accepted theories describing electromagnetic fields differ fundamentally from those describing strong fields. Therefore, the many similarities are quite surprising, and some are not adequately explained even today. Several such unexplained similarities are listed among the top open problems in particle physics, such as the “EMC effect,” the “proton spin crisis,” and the “strong CP problem.” This paper highlights, for the first time, the underlying common characteristics of these problems, potentially offering valuable contribution to future explanations.

Strong-aroma Baijiu is a traditional Chinese spirit distilled from grains that undergo solid-state fermentation. At the end of each fermentation cycle, a significant quantity of Huangshui accumulates at the bottom of the fermentation pit, constituting one of the primary by-products in the brewing process of strong-flavor liquor. In this report, the chemical component analysis of Huangshui obtained from a strong-flavor liquor factory revealed a diverse array of organic acids, alcohols, esters, starch, reducing sugars, amino acids, and other compounds present in Huangshui. Additionally, two specialized solid-state fermentation models were developed to investigate the formation process of Huangshui. Our findings demonstrate a positive correlation between the yield of Huangshui and the initial moisture content of fermented grains. It is concluded that Huangshui is the percolate produced during the solid-state brewing process of strong-flavor liquor, with its water content originating from the initial moisture of fermented grains.

In this paper, the authors employ Mountain Pass Lemma, the method of weak solution regularization and Lyapunov function method to derive the unique existence of globally exponential stable positive stationary solution of a single-species model with diffusion and delayed feedback. The obtained stability criterion illuminates that under some suitable conditions, a certain internal competition is conducive to the overall stability of the population, and a certain amount of family planning is conducive to the overall stability of the population. A numerical example and three tables show the effectiveness of the proposed methods.

QSO B0218+357 is a blazar located at a cosmological redshift of 0.944. The source is gravitationally lensed by a spiral galaxy located at the redshift of 0.68. Strong gravitational lensing splits the signals emitted by the source into two components separated by 10-12 days, as observed in radio and gamma-ray bands. In July 2014 a GeV flare was observed by Fermi-LAT, triggering follow-up observations with the MAGIC telescopes at energies above 100 GeV. The expected time delay between the components allowed us to plan broad band MWL observations before, during and after the trailing component of the emission. The MAGIC observations at the expected time of arrival of the trailing component resulted in the first detection of QSO B0218+357 in Very-High-Energy (VHE, >100 GeV) gamma rays. It is both the farthest known VHE object and one of only a few Flat Spectrum Radio Quasars detected in this energy range. We report here the observed multiwavelength spectral and temporal properties of the emission during the 2014 flare.

Alzheimer’s disease manifests itself as a complex pathological condition with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease current therapeutic strategies aim at a multitargeted approach often relying on a combination of sub-stances with versatile and complementary effects. In the present study, unique combination of α-lipoic acid, citicoline, extracts of leaves from olive tree and green tea, Vitamin D3, selenium and an immune supporting complex was tested in a scopolamine-induced dementia in rats. Using behavioral and biochemical methods we assessed the effects of this combination on learning and memory, and elucidated the mechanisms under-lying its effects. Our results showed that as compared to the components, experimental combination was most efficient in improving short- and long-term memory assessed by the step-through method as well as spatial memory, assessed by T-maze and Barnes maze underlying decrease in AChE activity and LPO, in-creases in SOD activity in cortex; activities of catalase and GPx, levels of BDNF and pCREB in the hippocam-pus. No significant histopathological changes or blood parameter changes were detected, making the experi-mental combination an effective and safe candidate in a multitargeted treatment of AD.

Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signalling pathways. The nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signalling has been implicated in a variety of chronic inflammatory diseases, which results in the release of pyroptotic cytokines, interleukin-1β (IL-1β) and IL-18. Likewise, the activation of the signal transducer and activator of transcription-3 (STAT3) causes increased expression of pro-inflammatory cytokines. We studied the effects of CBD and THC on lipopolysaccharide (LPS)-induced inflammatory response in human THP-1 macrophages and primary human bronchial epithelial cells (HBECs). Our results revealed that CBD and, for the first time, THC, significantly inhibited NLRP3 inflammasome activation following LPS + ATP stimulation, leading to a reduction in the levels of IL-1β in THP-1 macrophages and HBECs. CBD attenuated the phosphorylation of nuclear factor-κB (NF-κB) and both cannabinoids inhibited the generation of oxidative stress post-LPS. Our multiplex ELISA data revealed that CBD and THC significantly diminished the levels of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) after LPS treatment in THP-1 macrophages and HBECs. In addition, the phosphorylation of STAT3 was significantly downregulated by CBD and THC in THP-1 macrophages and HBECs, which was in turn, attributed to the reduced phosphorylation of tyrosine kinase-2 (TYK2) by CBD and THC after LPS stimulation in these cells. Overall, CBD and THC were found to be effective in alleviating the LPS-induced cytokine storm in human macrophages and primary HBECs, at least via modulation of NLRP3 inflammasome and STAT3 signalling pathways. The encouraging results from this study warrant further investigation of these cannabinoids in vivo.

A metastable β-Ti alloy, Ti–10V–3Fe–3Al (wt.%), was subjected to thermos-mechanical processing including the compression test at 725°C, which is below the β transus temperature (780°C), and at strain rate of 10-3s-1. The presence of phases was determined using transmission electron microscopy and X-ray diffraction. Although the dynamic recovery took place together with slip, both deformation-induced α˝ martensite and ω were detected as other operating mechanisms for the first time in metastable-β Ti alloys deformed in α+β region. The volume fraction of stress-induced α˝ was higher than that of the same alloy deformed at room temperature due to higher strain applied. Stress-induced twinning was not operational, which could be related to the priority of slip mechanism at high temperature resulted from thermally-assisted nucleation and lateral migration of kink-pairs.

To follow the growth and development of each tree (N = 1200) Pinus sylvestris L., var. Negorelskaya starting from the seed and continuing at the juvenile (or even generative) stage is the goal of an ambitious project to create a plant passport if possible. Five datasets of replenished empirical (tab-ular and file) and systematic data reflect the early results of a unique ongoing experiment conducted with families moved along a climatic gradient from the collection area (1731 degree days, 722 mm) to the experimental area (2326 degree days; 786 mm). Datasets of morphometric, VIS-spectrometric, and germination seed data, combined with the first results of biometric data (including the Dickson quality index) of seedlings produced from these seeds, will allow scientists in the future to conduct correlation and other statistical analysis, or train a neural network to determine the presence of connections between a seed and a plant. These data contribute to the early non-destructive diag-nosis and grading of seeds according to VIS-spectrometric properties. This dataset structure can complement the FLR-Library. In the future, by tracing seedlings in their early growth (for example, over three growing seasons at the site being restored), it will be possible to determine the degree of intensification of FRM production depending on the initial properties of the seed.

Rasagiline (Azilect®) is a selective monoamine oxidase B (MAO-B) inhibitor that provides symp-tomatic benefit in Parkinson’s disease (PD) treatment and found to exert preclinical neuroprotec-tive effects. Here, we investigated the neuroprotective signaling pathways of rasagiline in the PC12 neuronal cultures exposed to an ischemic-like insult. Exposure of neurons to oxy-gen-glucose deprivation for 4 h followed by 18 h of reoxygenation caused 40% aponecrotic cell death. Rasagiline induced dose-dependent neuroprotection by decreasing cell death and produc-tion of the neurotoxic reactive oxygen species, and reducing the nuclear translocation of glycer-aldehyde-3-phosphate dehydrogenase (GAPDH). Rasagiline increased protein kinase B (Akt) phosphorylation and decreased protein expression of the ischemia-induced α-synuclein protein, in correlation to the neuroprotective effect. Treatment with rasagiline induced nuclear shuttling of transcription factor Nrf2 and increased the mRNA levels of the antioxidant enzymes heme oxy-genase-1, (NAD (P) H- quinone dehydrogenase, and catalase. These results indicate that rasagiline provides neuroprotection in the ischemic neuronal cultures with inhibition of α-synuclein and GAPDH-mediated aponecrotic cell death, and via mitochondrial protection, as by increasing mi-tochondria-specific antioxidant enzymes by a mechanism involving the Akt/Nrf2 redox-signaling pathway. These findings may be exploited for neuroprotective drug development in PD and stroke therapy.

Understanding the phenomena underlying the non-selective susceptibility to ischemia of py-ramidal neurons in the CA3 area of the hippocampus is important from the point of view of elu-cidating the mechanisms of memory loss and the development of post-ischemic dementia. We used an ischemic model of Alzheimer's disease to study changes in amyloid protein precursor gene expression, its cleavage enzymes and tau protein in the CA3 area of the hippocampus af-ter a 10-minute brain ischemia with 12, 18, and 24-month survival. Quantitative reverse tran-scriptase PCR assay showed that the expression of all the genes that contribute to amyloid pro-duction was dysregulated within 2 years in the CA3 area of the hippocampus after ischemia. The expression of the amyloid protein precursor gene was above the control values at all times of the study. The expression of the α-secretase gene also exceeded the control values throughout the study. In contrast, the expression of the β-secretase gene reaching its maximum increase 12 months after ischemia, was below control values after 18 months and again above control values after 24 months of survival. Presenilin 1 and 2 gene expression was significantly elevated throughout the follow-up period, with peak expression of both genes occurring 12 months after ischemia. This suggests that the genes studied are involved in the non-amyloidogenic processing of amyloid protein precursor. Also, tau protein gene expression was significantly elevated throughout the observation period, and peak gene expression was present 12 months after is-chemia. Data indicate that an episode of brain ischemia with long-term survival causes damage and death of pyramidal neurons in the CA3 area of the hippocampus in a manner dependent on modified tau protein. Thus defining a new and important mechanism of pyramidal neuronal death in the CA3 area after ischemia. In addition tau protein gene modification after brain is-chemia is useful in identifying ischemic mechanisms occurring in Alzheimer's disease.

There exists an implicit potential limitation in every physical discoveries that has been implemented and understood. However, the limitations can be bounded within a safe limit to prevent any constructing theory to be free from errors. As, it’s the inert nature of the humans, to go far beyond the scope of experimental findings in order to pursue any studies with the sole help of logical reasoning and mathematics, the argument can be prevailed in the form of WEAK Clampdown Effect & STRONG Clampdown Effect. More, the theories are constructed out of physical nature, more the theory gets hypothetical without any finding evidence, but that does or doesn’t actually justify the phenomenon, that too with the more increment of KARDASHEV Scale, more moderate ways of experimentation got developed curbing down the limitations within the human limit of ‘ERRORS’, that does can be neglected by approximation. Relationship being cross-judgmental on the basis of the computational limits and calculation accuracy, leading to a soft singularity, as a warning, that if computer powers cannot be checked on the basis of error approximations, then this may lead to the hitting of a hard singularity, that in phase with the forbidden gap (or after the optimum limit that arises at the core constraints of nature) to prevent the computation being carried off with respect to super-intelligence machines that are cognitive capability oriented future computers responsible for self growth & reproduction with more improvement algorithm, restricting all forms of humanity & constraints the human growth by virtue of limiting capacities of the humans as compared to computers.

In this paper, we study a three step iterative scheme to approximate fixed points of Suzuki's generalized non-expansive mappings. We establish some weak and strong convergence results for such mappings in uniformly convex Banach spaces. Further, we show numerically that iterative scheme (1.8) converges faster than some other known iterations for Suzuki's generalized non-expansive mappings. To support our claim, we give an illustrative example and approximate fixed points of such mappings using Matlab program. Our results are new and generalize several relevant results in the literature.

Ferrocenium (Fc+) inherits a number of molecular/electronic properties from the neutral counterparts’ ferrocene (Fc) including the high symmetry. Both Fc+ and Fc prefer the eclipsed structure (D5h) over the staggered structure (D5d) by an energy of 0.36 kcal·mol-1. The present study using the recently developed excess orbital energy spectrum (EOES) shows that the open shell Fc+ cation exhibits similar conformer dependent configurational changes to the neutral Fc conformer pair. A further energy decomposition analysis (EDA) discloses that the reasons for the preferred structures are different between Fc+ and Fc. The dominant differentiating energy between the Fc+ conformers is the electrostatic energy (EEstat), whereas in neutral Fc, it is the quantum mechanical Pauli repulsive energy (EPauli). Within the D5h conformer of Fc+, the EOES reveals that the -electrons of Fc+ experience more substantial conformer dependent energy changes than the -electrons (assumed the hole is in a β orbital).

Polyunsaturated fatty acids (PUFAs) and antioxidants are important mediators in the central nervous system (CNS). Lipid derivatives may be used to generate endocannabinoids or prostanoids derived from arachidonic acid, which attenuates excitotoxicity in quadripartite synapses with a focus in astrocytes and microglia; on the other hand, antioxidants, such as glutathione (GSH) and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in young and senescent brain, as well as in degenerative conditions such as Alzheimer’s and Parkinson's diseases. Through literature review, we aimed to highlight recent data on the role of fatty acids, antioxidants and physical activity in physiology and in molecular mechanisms of brain senescence. Data indicate the complexity and essentiality of endogenous/dietary antioxidants for maintenance of the redox status and control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, feeding behavior, plasticity and memory mechanisms throughout aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and require additional efforts from researchers, clinicians and nutritionists in the field.

The interaction of electrons with strong laser fields is usually treated with semiclassical theory, where the laser is represented by an external field. There are analytic solutions for the free electron wave functions, which incorporate the interaction with the laser field exactly, but the joint effect of the atomic binding potential presents an obstacle for the analysis. Moreover, the radiation is a dynamical system, the number of photons changes during the interactions. Thus, it is legitimate to ask how can one treat the high order processes nonperturbatively, in such a way that the electron-atom interaction and the quantized nature of radiation be simultaneously taken into account? An analytic method is proposed to answer this question in the framework of nonrelativistic quantum electrodynamics. As an application, a quantum optical generalization of the strong-field Kramers-Heisenberg formula is derived for describing high-harmonic generation. Our formalism is suitable to analyse, among various quantal effects, the possible role of arbitrary photon statistics of the incoming field. The present paper is dedicated to the memory of Prof. Dr. Fritz Ehlotzky, who had significantly contributed to the theory of strong-field phenomena over many decades.

A novel approach for the long-term medical treatment of the inner ear is the diffusion of drugs through the round window membrane from a patient-individualized, drug-eluting implant, which is inserted in the middle ear. In this study, drug-loaded (10 wt% Dexamethasone) guinea pig round window niche implants (GP-RNIs, ~1.30 mm x 0.95 mm x 0.60 mm) were manufactured with high precision via micro injection molding (µIM, Tmold = 160 °C, crosslinking time of 120 s). The medical grade silicone elastomer MED-4244 (NuSil Technology LLC, Radnor, PA, USA) was used. Molds for µIM were 3D printed from a commercially available resin PlasGRAY V2 (Asiga, Alexandria, Australia, TG = 84 °C) via a high-resolution DLP process (xy-resolution of 32 µm, z-resolution of 10 µm, 3D printing time of about 6 h). Drug release, biocompatibility, and bio-efficacy of the GP-RNIs were investigated in vitro. GP-RNIs could be successfully produced. Wear of the molds due to thermal stress was observed. However, the molds are suitable for single use in the µIM process. About 10% of the drug load (8.2 ± 0.6 µg) was released after 6 weeks (medium: isotonic saline). The implants showed high biocompatibility over a time of 28 days (lowest cell viability ~80%). Moreover, we found anti-inflammatory effects over a time of 28 days in a TNF-α-reduction test. These results are promising for the development of long-term drug-releasing implants for human inner ear therapy.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is reasonable epidemiological cohort data to recommend surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommend that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) should consider HCC surveillance. NITs include fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US or if US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), can help to identify high risk of incident HCC in NAFLD patients. Innovative parameters including Mac-2 binding protein glycated isomer , type IV collagen 7S, free apoptosis inhibitor of macrophage, combination of single nucleoside polymorphisms are expected to be established. Considering a large number of NAFLD population, optimal screening tests must meet several criteria including high sensitivity, cost effectiveness and availability.

Plants offer a simpler and cheaper alternative to mammalian animal models for the study of Endoplasmic Reticulum glycoprotein folding Quality Control (ERQC). In particular, the Arabidopsis thaliana (At) innate immune response to bacterial peptides provides an easy means of assaying ERQC function in vivo. A number of mutants that are useful to study ERQC in planta have been described in the literature, but only for a subset of these mutants the innate immune response to bacterial elicitors has been measured beyond monitoring plant weight and some physio-pathological parameters related to the plant immune response. In order to probe deeper into the role of ERQC in the plant immune response, we monitored expression levels of the PHI-1 and RET-OX genes in the At ER α-Glu II rsw3 and the At UGGT uggt1-1 mutant plants, in response to bacterial peptides elf18 and flg22. The elf18 response was impaired in the rsw3 but not completely abrogated in the uggt1-1 mutant plants, raising the possibility that the latter enzyme is partly dispensable for ERF signalling. In the rsw3 mutant, seedling growth was impaired only by concomitant application of the At ER α-Glu II NB-DNJ inhibitor at concentrations above 500 nM, suggesting residual activity in this mutant. The study highlights the need for extending plant innate immune response studies to assays sampling EFR signalling at the molecular level.

To understand the mystery of final unification, in our earlier publications, we proposed two bold concepts: 1) There exist three atomic gravitational constants associated with electroweak, strong and electromagnetic interactions. 2) There exists a strong elementary charge in such a way that its squared ratio with normal elementary charge is close to reciprocal of the strong coupling constant. In this paper we propose that, can be considered as a compound physical constant associated with proton mass, electron mass and the three atomic gravitational constants. With these ideas, an attempt is made to understand nuclear stability and binding energy. In this new approach, nuclear binding energy can be fitted with four simple terms having one unique energy coefficient with a formula, where is an estimated mean stable mass number. With this new approach, Newtonian gravitational constant can be estimated in a verifiable approach with a model relation of the form, where is the Fine structure constant. Estimated and is 62 ppm higher than the CODATA recommended It needs further investigation. Proceeding further, an attempt is made to fit the recommended quark masses.

Lactic acid (LA) is a significant byproduct in Baijiu fermentation, with both D(-)-lactic acid (D(-)-LA) and L-lactic acid (L(+)-LA) being present due to the diverse microbial metabolism involved. L(+)-LA, a key industrial raw material, is metabolizable by humans, unlike D(-)-LA. This study aims to isolate microorganisms from fermented grains that preferentially produce L(+)-LA and apply these strains to Baijiu fermentation processes. We analyzed 106 commercially available Baijiu samples, along with fermented grains, yellow water, and Baijiu samples from 10 Baijiu factories, confirming the coexistence of D(-)-LA and L(+)-LA in fermentation products. Notably, a strong correlation was found between L(+)-LA in fermented grains and L-ethyl lactate (L(+)-EL) in Baijiu. Microbial community analysis revealed that Lactobacillus and Bacillus were the dominant bacterial groups, with a succession of microbial communities throughout fermentation. Two strains, A6 and B12, identified as Bacillus licheniformis and Bacillus cereus, respectively, were isolated for their high selectivity in L(+)-LA production. Both strains demonstrated a high yield of L(+)-LA in fermentation tests. Incorporating these strains into both liquid- and solid-state fermentation systems markedly increased the proportion of L(+)-EL relative to total ethyl lactate in Baijiu. This study successfully isolated and applied L(+)-LA-producing strains to fermentation models, offering a practical strategy for increasing L(+)-LA content in Baijiu.

In this paper, we make an attempt to estimate the famous Avogadro number with programming logics written in Python associated with advanced nuclear binding energy formulae. Average rest mass of nucleon, nuclear binding energy per nucleon and electron rest mass seem to play a vital role in estimating the unified atomic mass unit and Avogadro number. Interesting point to be noted is that, Avogadro number seems to be the inverse of the Unified atomic mass unit. With further study, it seems possible to estimate the unified atomic mass unit and Avogadro number accurately. Our interesting observation is that, short range strong nuclear force seems to have a vital role in deciding the accuracy of Avogadro number. For that purpose one may consider AI techniques along with newly observed atomic nuclides and their nuclear binding energies. For Z=6 to 118 and A_low=2Z and A_upper=3.5Z, estimated average value of Avogadro number is $N_{Average} \cong 6.01938 \times 10 ^{26}$. Considering the saturation of nuclear binding energy, at Z=26, $N_{Z=26} \cong \left(6.02229 \textrm{to} 6.02285\right) \times 10 ^{26}$. At academic level, our proposal can be given a chance as a case study. It is planned to develop a web application for this purpose.

It is extremely fascinating and astonishing that the gravitational field on the surface of a neutron star is with a relativistic mass density of 2.65*10¹⁶~5.87*10¹⁸kgm^-3 which can be larger than the mass density of the neutron star (~10¹⁷kgm^-3).Therefore, it is the author’s first intuitional imagining that this field could directly convert into mass. In so strong a gravitational field, electron and proton could be produced directly from graviton–photon collision. The gravitational field exists in everywhere in our universe. No vacuum that the region of a space is “empty” does exist. A particle is clearly always being acted on by the gravitational field. The quantum vacuum fluctuation and vacuum polarization need be re-understood with the interaction between photon and gravitational field. Therefore, the gravitational field is naturally one of the foundations of modern physics.

An attempt is made to model the atomic nucleus as a combination of bound and free or unbound nucleons. Due to strong interaction, bound nucleons help in increasing nuclear binding energy and due to electroweak interaction, free or unbound nucleons help in decreasing nuclear binding energy. In this context, with reference to proposed 4G model of final unification and strong interaction, recently we have developed a unified nuclear binding energy scheme with four simple terms, one energy coefficient of 10.1 MeV and two small numbers 0.0016 and 0.0019. In this paper, by eliminating the number 0.0019, we try to fine tune the estimation procedure of number of free or unbound nucleons pertaining to the second term with an energy coefficient of 11.9 MeV. It seems that, some kind of electroweak interaction is playing a strange role in maintaining free or unbound nucleons within the nucleus. It is possible to say that, strong interaction plays a vital role in increasing nuclear binding energy and electroweak interaction plays a vital role in reducing nuclear binding energy. Interesting observation is that, Z can be considered as a characteristic representation of range of number of bound isotopes of Z. For medium, heavy and super heavy atoms, beginning and ending mass numbers pertaining to bound states can be understood with 2Z+0.004Z^2 and 3Z+0.004Z^2 respectively. With further study, neutron drip lines can be understood. Based on this kind of data fitting procedure and by considering the mass ratio of pions and electroweak bosons, existence of our 4G model of electroweak fermion of rest energy 584.725 GeV can be confirmed confidently.

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p&lt;0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p&lt;0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p&lt;0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.

Background: In our recent publications pertaining to 4G model of final unification and based on strong and electroweak interactions, we have proposed the existence of a weak fermion of rest energy 585 GeV. Objective: To confirm the physical existence of the proposed 585 GeV weak fermion by analyzing weak and strong interactions in a unified approach via 4G model of final unification, super symmetry and string theory. Method: Considering the proposed nuclear charge of 2.95e, proton, electron mass ratio, specific charge ratios of proton and electron, Fermi’s weak coupling constant, Reduced Planck’s constant, nucleon magnetic moments, nuclear stability, nuclear binding energy, nuclear mass and neutron lifetime, it is planned to confirm the physical existence of the proposed 585 GeV weak fermion. Results: All proposed logics and formulae clearly establish the physical existence of 585 GeV weak fermion directly and indirectly. Conclusion: Believing in the physical existence of the proposed 585 GeV weak fermion, there is a scope for observing galactic TeV radiation coming by virtue of annihilation of 585 GeV fermions and radiation associated with various astrophysical acceleration mechanisms of 585 GeV fermions. Appeal: As we are beginners of astrophysics domain, we appeal the science community to see the possibility of considering the proposed 585 GeV weak fermion with a charge of $\pm\left(e\right)$ in place of electron and proton.

This study investigates the effectiveness of a range of timber-based solutions for seismic and energy retrofitting of existing masonry buildings. These solutions are designed not only to prevent structural collapse during earthquakes but also to create integrated interventions that enhance thermo-physical performance and reduce emissions in existing buildings. Various case scenarios were considered and both mechanical and energetic behavior post-intervention were evaluated. Timber-engineered products serve as foundational components for the retrofit approach, encompassing one-dimensional vertical elements (strong-backs) and various types of panels (cross-laminated timber panels, laminated veneer lumber panels, and oriented strand board panels). The analyzed retrofit techniques share a common principle, involving the attachment of these timber-based elements to the building's wall surfaces through mechanical point-to-point connections. The proposed solutions integrate strong-backs and timber panels with membranes and insulation layers, yielding cohesive and highly effective interventions. Finite element modeling was employed to analyze the mechanical and thermal responses of the retrofitted walls. A comprehensive comparative analysis of various techniques was conducted to determine the most effective solution for each specific scenario.

Previous studies generally reckon that the full converter-base wind power generation (FCWG) is a ’decoupled’ power source from the grid, which hardly participates in electromechanical oscillations. However, it is found recently that strong interaction could be induced which might incur severe resonance incidents in electromechanical dynamic timescale. In this paper, the participation of FCWG in electromechanical dynamics is extensively investigated, and particularly, an unusual transition of electromechanical oscillation mode (EOM) is uncovered for the first time. The detailed mathematical models of open-loop and closed-loop power systems are firstly established, and modal analysis is employed to quantify the FCWG participation in electromechanical dynamics, with two new mode identification criteria, i.e., FCWG dynamics correlation ratio (FDCR) and quasi-electromechanical loop correlation ratio (QELCR). On this basis, the impact of different wind penetration levels and controller parameter settings on the participation of FCWG is investigated. It is revealed that if an FOM has a similar oscillation frequency to the system EOMs, there is a high possibility to induce strong interactions between FCWG dynamics and system electromechanical dynamics of the external power systems. In this circumstance, an interesting phenomenon may occur that an EOM may be dominated by FCWG dynamics, and hence is transformed into a quasi-EOM, which actively involves the participation of FCWG quasi-electromechanical state variables.

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0=10.9; β=-4.27; p=0.04) and increased salivary α-amylase activity (β0=-3.55; β=2.68e-05; p=0.02,). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0=3.41; β=-0.99; p=0.047), smaller temporal pole volume (β0=3.41; β=-3.12; p=0. 06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0=3.41; β=-0.05; p=0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

A series of novel substituted isoxazolidine derivatives was synthesized through 1,3-dipolar cycloaddition reactions of α-aryl-N-methyl nitrones with various ethylene moieties, resulting in the formation of isoxazolidine derivatives. The structures of the synthesized compounds were characterized using spectroscopic methods. The [3+2] cycloaddition (32CA) reactions of α-aryl-N-methyl nitrones with diverse ethylene substituents were computed employing Density Functional Theory (DFT) at the B3LYP/6–31G(d) level, upgrading bond parameters. An investigation of the electron localization function (ELF) unveiled the zwitterionic nature of α-aryl-N-methyl nitrones, devoid of pseudoradical or carbenoid centers. Utilization of CDFT indices enabled the prediction of global electronic flux from the strongly nucleophilic α-aryl-N-methyl nitrones to the varied electrophilic ethylene functionalities. Molecular docking and molecular dynamics simulations were conducted on the isoxazolidine derivatives against the EGFR receptor (PDB: 4ZAU). In silico assessment of the synthesized isoxazolidines involved molecular docking, wherein the compound with the highest docking score was subjected to molecular dynamics simulations. Compound 11a, out of the thirty isoxazolidine derivatives, displayed the most substantial binding energy, yielding a g score of -6.57 kcal/mol. These observations highlighted the functional role of amide NH2 and NO2 in the binding process with the target protein, influencing its activity. Furthermore, prediction of ADME drug-likeness properties was performed to identify a suitable candidate.

In real-life scenario, there are many mathematical tools to handle the incomplete and imprecise data. One of them is the fuzzy approach. This article aims to contribute to the literature of fuzzy multi-objective dynamic programming issues involving the fuzzy objective functions. The piecewise quadratic fuzzy numbers characterize these fuzzy parameters. Some basic notions in the problem under the α-pareto optimal solution concept is redefined and analyzed to study the stability of the problem. Furthermore, a technique, named as enhancing decomposition approach, is presented for achieving a subset for the parametric space that contains the sameα-pareto optimal solution. For a better understanding and comprehension of the suggested concept, a numerical example is provided.

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

The production of particles outside the region of nucleon-nucleon kinematics due to interactions involving dense cold clusters of quark-gluon matter in nuclei is calculated. The possibility of observing this process in the region of central rapidities and large transverse momenta in heavy ion collisions at low energies with MPD detector at the NICA collider has been demonstrated.

The term ‘Hallmarks of Cancer’ was coined by Hanahan and Weinberg in their influential reviews and they described genome instability as a property of cells enabling cancer development [1, 2]. Accurate DNA replication of genomes is central to diminish genome instability. Here, the understanding of the initiation of DNA synthesis in origins of DNA replication to start leading strand synthesis and the initiation of Okazaki fragment on the lagging strand are crucial to control genome instability. Recent findings have provided new insights into the mechanism of the remodelling of the prime initiation enzyme, DNA polymerase α-primase, during primer synthesis, how the enzyme complex achieves lagging strand synthesis, and how it is linked to replication forks to achieve optimal initiation of Okazaki fragments. Moreover, the central roles of RNA primer synthesis by Pol-prim in multiple genome stability pathways such as replication fork restart and protection of DNA against degradation by exonucleases during double-strand break repair is discussed.

In this paper, we introduce a new formulation based on Floquet (Fourier) spectral analysis combined with a spectral modulation technique (and its spatial form) to study strongly coupled sublattices predefined in the infinite and large finite extent of almost periodic antenna arrays (e.g metasurfaces). This analysis is very relevant for dense massive MIMO, intelligent surfaces, 5G, and 6G applications (used for very small areas with a large number of elements such as millimeter and terahertz waves applications). The numerical method that is adopted to model the structure is the method of moments simplified by equivalent circuits MoM GEC. Other numerical methods (as the ASM array scanning method and windowing Fourier method) used this analysis in their kernel that to treat periodic and pseudo-periodic (or quasi-periodic) arrays.

This article is some review of results that were obtained at 2007-2021 years development of “The Information as Absolute” concept and the informational physical model, which is based on the concept; including a number of fundamental physical problems are briefly considered in framework of the conception and the model. Recently in physics there are several publications, that present lists of the problems. However, those lists are essentially incomplete, for at least two reasons. Firsts of all, a number of phenomena are studied traditionally by philosophy, and so corresponding problems are usually considered to be “metaphysical”. However, they relate also to some concrete physical phenomena. For example, physics evidently studies Matter, and so the metaphysical problems “what is ontology of Matter”, “what is “Space”, “Time” and a few other physical phenomena and notions as well, are really a Meta-physical problems “what does physics study?” There are other fundamental physical problems, which are not considered as such in physics, and are absent in the “fundamental problems lists”. Those include the problems, which really exist, yet are incorporated into standard physical theories, and so are fundamental “implicitly”, which in physics are “solved by default” ‒ and mostly erroneously. Note, though, that a number of “Meta-physical”, and concrete fundamental, problems more in detail are considered in the paper “The Informational Conception and Basic Physics”, https://arxiv.org/abs/0707.4657, v5 (2021), so this paper is, in certain sense, an expanded conclusion of this paper, which includes, correspondingly, more in detail consideration of some more general physical problems; and, besides, in this article, the problem “what are Gravity and Electric Forces” is essentially clarified comparing with the arXiv 2021 paper version above, and additionally initial model of Nuclear Force is presented. Besides, the concrete problem “What is Life”, and the rational cosmological model, where a few vague points in standard cosmology rather probably are rationally clarified, while the fundamental problem “matter – antimatter asymmetry” in Matter is solved with rather large probability, are considered, and one of recently published rather complete “lists of fundamental problems” is commented in Appendix.

Our previous studies showed that in patients with brain diseases neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in control of neuronal networks in epileptic brain, we aimed to assess GDNF levels in LF and BS as well as BDNF, hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (PWFE), epilepsy and comorbid depression (PWFE+MDD) compared with major depressive disorder (PWMDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in PWFE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. LF and BS GDNF concentrations positively correlated in HC, but not patient groups. BDNF level was lower in BS of patients compared with HC and higher in PWFE+MDD taking valproates. Logistic regression models demonstrated that GDNF decrease in LF may be an important predictor of focal epilepsy. Probability of focal epilepsy can be evaluated using GDNF in LF and BDNF in BS; MDD - GDNF in LF, cortisol and TNF-α in BS; epilepsy with MDD - GDNF in LF, TNF-α and BDNF in BS.

We propose a new theory beyond the standard model of elementary-particle physics. Employing the concept of a quantized spacetime, our theory demonstrates that the zero-point energy of the vacuum alone is sufficient to create all the fields, including gravity, the static electromagnetic field, and the weak and strong interactions. No serious undetermined parameters are assumed. Furthermore, the relations between the forces at the quantum-mechanics level is made clear. Using these relations, we quantize Einstein’s gravitational equation: Beginning with the zero-point energy of the vacuum, and after quantizing Newtonian gravity equation, we combine the energies of a static electromagnetic field and gravity in a quantum spacetime. Applying these results to the Einstein gravity equation, we substitute the energy density derived from the zero-point energy in addition to redefining differentials in a quantized spacetime. This is how we derive the quantized Einstein gravitational equation without assuming the existence of macroscopic masses. For the weak interaction, by considering plane-wave electron and the zero-point energy, we obtain a wavefunction that represents a β collapse. In this process, from a different point of view than Weinberg-Salam theory, we derive the masses of the W and Z bosons and the neutrino, and we calculate the radius and lifetime of the neutron. For the strong interaction, we previously reported an analytical theory for calculating the mass of a proton by providing a specific linear attractive potential obtained from the zero-point energy, which agrees well with the measurements. In the present study, we further calculate the strong interaction between two nucleons, i.e., the mass of the pi-meson. The resulting calculated quantities agree with the measurements, which verifies our proposed theory.

The sexual reproduction of ascomycetes is controlled by the mating-type(MAT) locus. (Pseudo)homothallic reproduction has been hypothesized based on genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). In this study, the differential occurrence of the mating-type genes in the MAT1-1 and MAT1-2 idiomorphs, which constitute the genetic control of O. sinensis reproduction, was analyzed in 237 strains and 5 genomes of H. sinensis. The mating-type genes were differentially transcribed in H. sinensis Strain L0106, and the MAT1-2-1 transcript in H. sinensis Strain 1229 was alternatively spliced, with an unspliced intron I containing stop codons; these findings constitute O. sinensis reproduction controls at the transcriptional and coupled transcriptional-translational levels. The occurrence of the mating-type genes and a-/α-pheromone receptor genes differed among the 5 H. sinensis genomes. The differential occurrence and transcription of these genes are inconsistent with self-fertilization under (pseudo)homothallism but suggest self-sterility of H. sinensis, which therefore needs a mating partner to achieve sexual outcrossing under heterothallism or hybridization. Consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis, but these findings are insufficient to determine the reproduction mode(s) because of the co-occurrence of >90 fungal species and multiple genomically independent genotypes of O. sinensis. The mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in the N-terminus or middle-truncated proteins, with changes in hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction.