Activation of the EGFR pathway plays an important role in the progression of cancer and is associated with a poor prognosis in patients. The monoclonal antibody cetuximab, which displays EGFR extracellular domain-specific binding, has proven effective in the treatment of locally advanced disease and relapsed/metastatic disease. However, the effects of cetuximab are weaker than those of EGFR tyrosine kinase inhibitors (TKIs). This study investigates differences in the effects on cell growth of cetuximab and EGFR TKI AG1478 at the molecular level using oral squamous cell carcinoma (OSCC) cell lines. First, we found that there were EGFR-inhibitor sensitive (EIS) and EGFR-inhibitor resistant cell lines. The EIS cell lines expressed not only EGFR but also ErbB3, and both were clearly phosphorylated. The levels of phosphorylated ErbB3 were unaffected by cetuximab but were reduced by AG1478. EGFR ligand treatment increased the levels of phosphorylated EGFR but not phosphorylated ErbB3. Moreover, when EIS cell lines that were only capable of anchorage-dependent growth were grown in suspension, cell growth was suppressed and the levels of phosphorylated FAK, Src, and ErbB3 were significantly reduced. The levels of phosphorylated ErbB3 were unaffected by the FAK inhibitor PF573228, but were reduced by Src inhibition. Finally, combining cetuximab and a Src inhibitor produced an additive effect on the inhibition of EIS cell line growth.

The current report contributes to the understanding of the stereoselectivity of the chiral dirhodium(II) carboxylate catalysts derived from N-protected amino acid ligands. Investigating the possible effect of ligand stereo-purity on catalyst structure and enantioselectivity was carried out. This was justified through a new X-ray crystal structure for Rh2(S,S,S,R-PTTL)4 diastereomer.

Calorie restriction (CR) has been shown to prolong the lifespan of humans, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-D-glucose, D-glucosamine, and D-allulose, which show anti-aging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.

Multiple myeloma (MM) accounts for about 10 to 15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60-minute workouts 3 times a week was conducted. Body mass and composition and the levels of: vitamin D, calcium and phosphorus, beta2-microglobulin and albumin were examined before and after completion of training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN) and Tartrate-resistant acid phos-phatase 5b (TRACP 5b). There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumines was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p=0.001 and p=0.022, re-spectively). The change in the concentration of this vitamin negatively correlated with the con-centration of TRACP 5b (r=-0.413, p=0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p=0.026, time vs. group: p=0.033) and TRACP 5b (time: p

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

At present European buildings typically consume two to five times more energy than predicted at the design stage. An important cause of this performance gap is the discrepancies between the design specification and the As-Built condition. Such discrepancies are mainly due to the gaps in knowhow between design, production and construction professionals. Design is more and more contained into a virtual environment and loses touch with the physical production and construction sites. As the construction sector enters the Industry 4.0 era, Building Information Modelling (BIM) based Mixed Reality can intertwine virtual and real worlds to bridge the knowhow gaps.

The aim of this work is to present a design approach of a Shock-Induced Combustion Ramjet (Shcramjet) inlet, and present its optimization in terms of the flow and geometrical parameters. The flow properties of mixed compression type inlet of a Shcramjet are examined using analytical and numerical techniques. The geometries obtained with variations in the wedge angles, length, height and cowl lip positions are used to study the flow characteristics of inlet, identifying bow shock temperature ratio as the optimization parameter. The two-dimensional geometries of two-shock and three-shock inlet models designed analytically for shock-on-lip condition at Mach 12.5 and an altitude of 32.5 km are numerically simulated in OpenFOAM CFD Toolbox. A density based compressible CFD solver based on central upwind schemes of Kurganov and Tadmore is used to solve 2D inviscid Euler equations. The inlet total pressure recovery is expressed as a function of temperature ratios of compression shocks, and is found to have a maxima at a bow shock temperature ratio at the design condition when the bow and external shocks have equal strengths. The effect of considering the flow to be calorically imperfect is studied numerically, and the deviation from the analytical design is presented.

Abstract: COVID-19 in 2020 brought challenges to the Brazilian public health system with an emerging virus with respiratory contagion called SARS-CoV-2. There are few studies in Brazil and in some countries, on the increased incidence of certain viral respiratory infections, includ-ing H1N1 and coronavirus and their association with low levels of vitamin D, zinc and iron. The aim of this study was to demonstrate that the deficit of vitamin D, zinc and iron has an impact on the infectious process of patients with COVID-19 and to establish new forms of prevention for the worsening of COVID-19 in the human body. Data were collected from medical records and test results from patients being followed up during the treatment period for COVID-19. Patients with low blood levels of vitamin D, zinc and iron during the treatment period of COVID-19 had a higher percentage of worsening and complications requiring hospitalization in intensive care beds. The ingestion of vitamin D, zinc and iron in the treatment period of patients with COVID-19 in addition to being an immunological protector against SARS-CoV-2 and alleviating the process of worsening the disease can also act as a biomarker in cases of this disease.

The outbreak of Coronavirus, as well as its emerging potential consequences, has become a global challenge worldwide, demanding effective and controlled therapeutic strategies. Potential drug candidates could achieve that with minimal toxicity. The current investigation selected 2-Deoxy-D-glucose prescribed by Defense Research and Development Organization (DRDO), India. The derivative and modified form was tested through in silico analysis against COVID-19 main protease complex with N3 inhibitor. The derived form of 2-Deoxy-D-glucose was generated by replacing the hydroxy group with a hydrogen atom, and Cypate 2-Deoxy-D-glucose was chosen as a derivative against the COVID-19 main protease complex. A molecular docking approach was adopted to identify the stable and competent form among the modified and derivative forms of 2-Deoxy-D-glucose based on binding energy. By further promoting the stabilized complex, these compounds' toxicity was also scrutinized through ADMET analysis to predict the potential candidate. The current investigation suggested that the modified version of 2-Deoxy-D-glucose was more stable with minimal toxicity against COVID-19 main protease.

Revenue-sharing (RS) contracts are a common approach to incentivize innovation of upstream suppliers by addressing the uneven profit distribution between upstream and downstream firms. Considering the possible overconfidence characterizing decision makers in the supply chain, we investigate the effect of the RS contract and the tendency of overconfidence of supply chain members on the investment in R&D of key components of products in the context of an upstream supplier that is the leader in the R&D and production of key components. We find that regardless of the bargaining power of either party, a RS contract can increase the R&D investment in key components. Regarding the effects of overconfidence of either downstream manufacturer or up-stream supplier, it can increase the R&D investment in key components. Supplier (manufacturer) overconfidence can harm their own profits but increase the profits of the manufacturer (supplier), and when the level of overconfidence is below a certain threshold, the damage to their own profits is less than the increase in each other's profits, thus benefiting the whole supply chain. In addition, we also find a joint effect of RS contracts and overconfidence: when the bargaining power of the supplier is low, the RS contract has a certain compensatory effect on the loss of their own profits caused by overconfidence.

Long Covid has become a blight, its economic consequences overwhelming. But Long Covid (LC) may represent persistent Covid-19 in those with preexisting Candida overgrowth (CO). The features shared by both are striking. LC may be a growing subset of CO. The altered tryptophan metabolism encountered in LC is driven by IFN-γ in reaction to CO. Females are robust producers of IFN-γ, yet estrogen promotes CO.The consequent decline in serotonin and melatonin triggers the mood swings and sleeplessness respectively in LC. The low serotonin, the primary messenger in the gut brain axis, creates autonomic dysfunction. The CO induced gut dysbiosis and leaky gut initiate an autoimmune path. TNFα seen in both LC and this opportunistic yeast is at the center of the cytokine triad that leads to neurodegeneration. The Western diet, high in carbohydrates, alcohol, and glutamate, is exploited by this commensal turned parasite. Residual SARS CoV2 and Candida generate abundant ROS, inducing mitochondrial dysfunction. Alcohol tastes different for many with LC, because acetaldehyde requires functioning hepatic mitochondria. This article delves into the complex physiology and biochemistry that drive the symptoms of this conspicuous connection. Recent research has revealed innovative approaches that might address this global scourge, including D-mannose for the immune dysfunction and butyrate for the gut dysbiosis created by and seen in both LC and intestinal Candidiasis.

With the continuous improvement and observable benefits of electric vehicles (EVs), major logistic companies are introducing more EVs into their conventional fleets. This gives rise to a new type of vehicle routing problem with mixed vehicles, where heterogeneous internal combustion vehicles (ICVs) and electric vehicles are considered in route planning. In addition, certain deliveries that are not efficient on any type of vehicles, are outsourced to third-party common carriers. In this paper, we define this problem as a mixed vehicle routing problem with common carriers (MVRPC). The objective of such problems is to minimize the transportation costs by considering routes with ICVs and EVs, the possibility of visiting recharging stations, outsourcing options, and drivers’ layover regulations. This variant of the vehicle routing problems has many practical applications, particularly in the design of long-haul transportation and last-mile delivery services. Effective MVRPC solutions play a key role in promoting the going Green image and optimally allocating resources. The problem has received limited attention in the literature likely because addressing all the needed aspects is especially challenging. To solve the large-scale problem, we develop a branch-and-cut pricing framework that relies on strong cuts and customized labeling algorithms. Numerical experiments highlight the effectiveness of our algorithm. This success can be attributed to tailored critical resources, dynamically bounded bidirectional labeling procedures, strong dominance criteria, and implementation strategies.

Background: Targeting Hepatitis B virus (HBV) infection in human is crucial due to its adverse. Herbal medicine has long been significant in this regard, with flavonoids demonstrating promising results. Hence, establishing a way of identifying flavonoids with anti-HBV activities is the aim of the present study. Methods: Flavonoid structures with anti-HBV activities were retrieved. A flavonol-based pharmacophore model was established using LigandScout v4.4. Screening was performed using the PharmIt server. A QSAR equation was developed and validated with independent sets of compounds. Applicability domain (AD) was defined using Euclidean distance calculations for model validation. Results: The best model, consisting of 57 features was generated. HTS using the flavonol-based model resulted in 509 unique hits. The model's sensitivity and specificity were 71% and 100%, respectively. The QSAR model with two predictors, x4a and qed, exhibited strong predictive performance with an adjusted-R² value of 0.85 and 0.90 of Q2. Conclusion: The QSAR model has been validated with two separate chemical sets, guaranteeing the model's reproducibility and usefulness for other flavonols by utilizing the predictive characteristics of X4A and qed. These results provide new possibilities for discovering future anti-HBV drugs by integrating modeling and experimental research.

A Pt(II) complex featuring chelating tridentate bis-aryloxide tetrahydropyrimidinium based N-heterocyclic carbene (NHC) was synthesized and characterized by using different techniques. The electrochemical properties of the complex were investigated by cyclic voltammetry as well as differential pulse voltammetry, which revealed two reversible one-electron oxidation processes. The chemical generation and isolation of one-electron-oxidized species were performed oxidizing the initial complex by means of AgBF4. The combined UV-Vis/NIR- and EPR-spectroscopy studies supported by density functional theory (DFT) calculations suggest the formation of Pt(II)-phenoxyl radical complex. The latter open-shell derivative was structurally characterized by means of X-ray diffraction analysis. Finally, the neutral platinum complex was tested as a mediator in the process of electrocatalytic oxidation of 2-(methylamino)ethanol (MEA).

Two solvated rhenium(IV) complexes with formula [ReCl4(bpym)]·MeCN (1) and [ReCl4(bpym)]·CH3COOH·H2O (2) [bpym = 2,2'-bipyrimidine] have been prepared and characterized by means of Fourier transform infrared spectroscopy (FT–IR), scanning electron microscopy and energy dispersive X-ray analysis (SEM–EDX), single-crystal X-ray diffraction (XRD) and SQUID magnetometer. 1 and 2 crystallize in the monoclinic system with space groups P21/n and P21/c, respectively. In both compounds, the Re(IV) ion is six-coordinate and bound to four chloride ions and two nitrogen atoms of a 2,2’-bipyrimidine molecule forming a distorted octahedral geometry around the metal ion. In the crystal packing of 1 and 2, intermolecular halogen⋯halogen and π⋯halogen type interactions are present. Hydrogen bonds take place only in the crystal structure of 2. Both compounds exhibit an akin crystal framework based on halogen bonds. Variable-temperature dc magnetic susceptibility measurements performed on microcrystalline samples of 1 and 2 show a similar magnetic behavior for both compounds, with antiferromagnetic exchange between the Re(IV) ions connected mainly through intermolecular Re-Cl···Cl-Re interactions.

Origins of the time, mass, electric charges and magnetic monopoles are explained. The energies, electric charges and magnetic charges of the particles are defined as E = cDtDV and |q| = cDt = E/DV, and |q_m| = c²Dt, respectively, for the 3-D quantized spaces warped along the time axis direction of ct in the 4-D Euclidean space. The energy (or mass) and charges (or electric charges and magnetic charges) are the vectors along the time axis of ct in the 4-D Euclidean space. This new concept is closely connected to the wave function of the quantum mechanics. The electric charges, magnetic charges and energies have the property of the space direction independence. Magnetic monopoles (charges) are the force carrying bosons with the inside electric field time loop. Electric monopoles are the elementary fermions. Photon space fluctuations are explained with the quantized magnetic charges.

The design of a mixed-mode proportional-integral-derivative (PID) controller circuit using current-feedback operational amplifiers (CFOAs) as active components is proposed. With the same circuit topology, the proposed configuration of three CFOAs, four resistors, and two capacitors is capable of performing the PID controller in all four operation modes: namely voltage mode, trans-admittance mode, current mode, and trans-impedance mode. Numerous mathematical analyses are conducted to determine the controller performance under ideal and non-ideal conditions. Additionally, the mixed-mode second-order lowpass filter is suggested, and also used to examine the workability of the proposed mixed-mode PID controller in a feedback control structure. The proposed PID controller is implemented with the commercially available IC-type CFOA AD844, and the simulation results are presented to illustrate the functionality of the controller and its closed-loop control system.

When the majority of museums and other cultural institutions were shut down due to the pandemic, mixed museum visits became a hot issue. After the epidemic, mixed visits, in the opinion of many experts, would become the new norm for experiencing cultural content. Diverse types of merging online and onsite visits are already being investigated by researchers, not only to avoid the spread of a disease but also to enable visits of people who were previously excluded, such as persons in remote geographic areas or people with mobility challenges. The current work takes into account the Contextual Model of Museum Learning to define potential use scenarios for visits from people of different cultural backgrounds and offers an evaluation of current practices.

Anomaly Detection in real time data is accepted as a vital research area. Clustering has effectively been tried for this purpose. As the datasets are real time, the time of generating of the data is also important. In this article, we introduce a mixture of partitioning and agglomerative hierarchical approach to detect anomalies from such datasets. It is a two-phase method which follows partitioning approach first and then agglomerative hierarchical approach. The dataset can have mixed attributes. In phase-1, a unified metric defined on mixed attributes is used. The same is also used for merging of similar clusters in phase-2. Also, we have kept the track of time attribute of each data instance which produces the clusters with their lifetimes in phase-1. Then in phase-2, we merge the similar clusters. While merging, the similar clusters, the lifetimes of the corresponding clusters with overlapping cores are to be superimposed producing fuzzy time intervals. This way, each cluster will have an associated fuzzy lifetime. The data instances either belonging sparse clusters or not belonging to any of the clusters can be treated as anomalies. The efficacy of the algorithms can be established using both complexity analysis as well as experimental studies.

In a safety-critical system typically not all provided services have the same criticality, which we call mixed-criticality systems. Criticality arithmetic, also called SIL arithmetic, is an approach to lower the development effort of a service by providing redundancy with tasks that are developed for a lower criticality level. In this paper we present ATMP-CA, which is a derivation of the multi-core scheduler ATMP. ATMP-CA is able to take into account the knowledge about the use of criticality arithmetic. ATMP-CA has a modified core allocation and procedure for utility optimisation, considering the context of the replicated tasks. We conducted experiments that show that ATMP-CA is able to provide the services using criticality arithmetic, while the reference schedulers were not.

In this study, a mixed rule of degree of precision nine has been developed and implemented in the field of electrical sciences to obtain the instantaneous current in the RLC- circuit for particular value .The linearity has been performed with the Volterra’s integral equation of second kind with particular kernel . Then the definite integral has been evaluated through the mixed quadrature to obtain the numerical result which is very effective. A polynomial has been used to evaluate Volterra’s integral equation in the place of unknown functions. The accuracy of the proposed method has been tested taking different electromotive force in the circuit and absolute error has been estimated.

In fuzzy group decision making problems and fuzzy shortest path problems, the addition and subtraction are the basic problems. For the mixed normal fuzzy numbers and trapezoidal fuzzy numbers, the addition and subtraction operations are approximated by the normal fuzzy numbers in this paper. The behaviors of approximated normal fuzzy numbers are the same as those of the normal distributions from the viewpoint of probability. An application of the addition and subtraction operations of mixed fuzzy numbers to the fuzzy sample mean is also proposed.

Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections - in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. Methods: PRISMA systematic review approach was applied; Delphi Panel method used to target consensus on statements retrieved from evidence. Results: Based of regulatory definitions and research evidences, the mechanism of D-mannose does not involve a metabolic or immunological action while there is an uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. Conclusions: From a regulatory perspective, D-mannose maintains the current medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose.

This article shows how to establish expansion formulas for calculating the mixed operations $(A^{\dag})^{\#}$, $(A^{\#})^{\dag}$, $((A^{\dag})^{\#})^{\dag}$, $((A^{\#})^{\dag})^{\#}$, $\ldots$ of generalized inverses, where $(\cdot)^{\dag}$ denotes the Moore--Penrose inverse of a matrix and $(\cdot)^{\#}$ denotes the group inverse of a square matrix. As applications of the formulas obtained, the author constructs and classifies some groups of matrix equalities involving the above mixed operations, and derives necessary and sufficient conditions for them to hold.

New families of direct serendipity and direct mixed finite elements on general planar, strictly convex polygons were recently defined by the authors. The finite elements of index r are H1 and H(div) conforming, respectively, and approximate optimally to order r+1 while using the minimal number of degrees of freedom. The shape function space consists of the full set of polynomials defined directly on the element and augmented with a space of supplemental functions. The supplemental functions were constructed as rational functions, which can be difficult to integrate accurately using numerical quadrature rules when the index is high. This can result in a loss of accuracy in certain cases. In this work, we propose alternative ways to construct the supplemental functions on the element as continuous piecewise polynomials. One approach results in supplemental functions that are in Hp for any p≥1. We prove the optimal approximation property for these new finite elements. We also perform numerical tests on them, comparing results for the original supplemental functions and the various alternatives. The new piecewise polynomial supplements can be integrated accurately, and therefore show better robustness with respect to the underlying meshes used.

Alzheimer's disease (AD) is characterized by memory impairment and existence of amyloid-β (Aβ) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM) - Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus - cultivated on a barley medium, was assessed for its anti-AD effects. A neuron-like PC12 cells, which were subjected to Zn2+, an Aβ aggregator, was employed as an in vitro AD model. The cells pretreated with or without MMMM assayed for Aβ immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aβ immunofluorescence, ROS accumulation, and apoptosis, and increment in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aβ plaques accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aβ plaque accumulation, and neuroinflammation, by impeding Aβ-induced neurotoxicity.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of D-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 D-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of L- and D-amino acids can potentially act as essential building blocks of life.

Age-related declines in vitamin D receptor (VDR) expression have been implicated in the onset of sarcopenia. The increased expression of VDR in muscle is known to increase muscle mass, whereas VDR knockout in the muscle decreases muscle mass in rats. Similar to VDR, the age-related decline in protein deacetylase sirtuin (SIRT) expression is linked to the development of sarcopenia and age-related muscle dysfunction. This study aimed to investigate whether the VDR agonist 1,25-dihydroxyvitamin D3 (1,25VD3) exerts beneficial effects on muscles through interactions with sirtuins and, if so, the underlying molecular mechanisms. 1,25VD3 treatment increases the expression of VDR, SIRT1, and SIRT3 in C2C12 myotubes. Additionally, it stimulates the differentiation of C2C12 myoblasts into myotubes. Furthermore, 1,25VD3 significantly enhanced the expression of key myogenic markers, including myosin heavy chain (MyHC) proteins (MyHC I and II), MyoD, and MyoG, and increased the phosphorylation of AMPK and AKT. Conversely, VDR knockdown in myoblasts induces myotube atrophy by downregulating SIRT1 and SIRT3 expression. Furthermore, 1,25VD3 ameliorated muscle atrophy and apoptosis induced by IFN-γ/TNF-α co-treatment to C2C12 myotube. Moreover, 1,25VD3 downregulated the increased expression of muscle atrophy-associated proteins, including FoxO3a, MAFbx, and MuRF1 in IFN-γ/TNF-α induced atrophy model. Importantly, IFN-γ/TNF-α significantly reduced the mtDNA copy number in C2C12 myotube, whereas the presence of 1,25VD3 effectively prevented this decrease. These results indirectly suggest that 1,25VD3 has the potential to develop as a therapeutic or preventive agent for age-mediated muscle atrophy by enhancing the VDR/SIRT1/SIRT3 axis and inhibiting the FoxO3-mediated atrophy pathway.

The purpose of this research was two-fold: (a) to observe whether highly trained adolescent swimmers abide to vitamin D supplement recommendations; and (b) to monitor changes in circulating 25-hydroxyvitamin D (25(OH)D) that occur between the autumn and winter months. Twenty swimmers (age: 17 ± 2 years) from a UK high-performance swimming club volunteered to complete two blood spot cards to determine 25(OH)D concentration: the first in an autumn training phase (October) and the second during winter training (January). All swimmers were advised to consume vitamin D3 supplements across the assessment period; however, only 50% of swimmers adhered to this recommendation. Resultantly, a winter decline in 25(OH)D was observed in non-supplementing swimmers (79.6 ± 25.2 to 52.6 ± 15.1 nmol·L-1, p = 0.005), with swimmers either displaying an ‘insufficient’ (60%) or ‘deficient’ (40%) vitamin D status. In comparison, greater maintenance of 25(OH)D occurred in supplementing swimmers (92.0 ± 25.5 to 97.2 ± 38.3 nmol·L-1, p = 0.544), although variable outcomes occurred at the individual level (four increased, three maintained, three declined). These findings highlight possible risks of vitamin D insufficiency during the winter for swimmers in the UK, possibly requiring standardised supplement practices. Moreover, alternative educational strategies may be required for swimmers to transfer knowledge to practice in order to improve supplement adherence in future.

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

A dioxomolybdenum catalyst [(MoO2Cl2-O-MoO2Cl2)(L)] (1) (with L (1S,2S)-N,N´-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex showed to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, occurring the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) showed to be influenced by the presence of water in the system. Using 50% aq. H2O2 it was possible to reuse the catalyst and the extraction solvent MeOH during ten consecutive cycles without loss of desulfurization efficiency.

This review explores the integration of Virtual and Mixed Reality in medical training. The advent of immersive technologies has revolutionized traditional methodologies, offering immersive, interactive, and flexible learning environments. This study aims to assess the impact, efficacy, and potential of Extended Reality (XR) in medical education. Methods included a comprehensive analysis of current Metaverse’s applications in various medical fields, including surgery, diagnostics, and patient care. Results indicate a significant enhancement in learning outcomes, practical skills, and student engagement. Conclusions suggest that Virtual Reality is a valuable tool for medical training, providing realistic simulations and improving both theoretical knowledge and practical skills. The intersection of virtual reality and cognitive neuroscience presents an exciting frontier for understanding the human brain's response to immersive environments. This review explores how VR impacts learning, with a particular focus on the activation and engagement of the prefrontal cortex during immersive experiences. It delves into various studies that highlight the transformative potential of VR in educational settings and therapeutic applications, demonstrating how VR can facilitate deeper and more effective learning experiences. The review will present a dedicated section on the current methodologies used to analyze the brain's response while immersed in a virtual environment.

A major challenge of augmented and mixed reality applications is identifying the context and semantics of the real environment. Studies on object and action recognition were developed based on the improvement of machine learning techniques, allowing them to be annotated and recognized. This study aims to characterize current knowledge on the use of machine learning for recognizing objects and actions in augmented and mixed reality environments, increasing context awareness. Therefore, a systematic literature review of works related to these topics was made, using the Scopus and Web of Science knowledge bases. We searched articles and conference reviews or papers published between 2018 and 2022 and selected fifteen studies to be reviewed. The results indicate that there is a great demand for using machine learning to immersive technologies in factories, engineering, entertainment, education, health, among other application domains. However, these real-time interactive systems still have challenges and limitations to be solved, involving network communication, prediction time and the creation of a model that recognize objects and actions in broad contexts. Furthermore, additional research is needed to investigate how object and action recognition can increase context awareness in augmented reality applications.

We describe the direct formation of mixed-phase (1T and 2H) MoS2 layers on Si as a photocathode via atomic layer deposition (ALD) for application in the photoelectrochemical (PEC) reduction of water to hydrogen. Without typical series-metal interfaces between Si and MoS2, our p-Si/SiOx/MoS2 photocathode showed efficient and stable operation in hydrogen evolution reactions (HERs). The resulting performance could be explained by spatially genuine device architectures in three dimensions (that is, laterally homo and vertically heterojunction structures). The ALD-grown MoS2 overlayer with the mixed-phase 1T and 2H homojunction passivates light absorber and surface states and functions as a monolithic structure for effective charge transport within MoS2. It is also beneficial in the operation of p-i-n heterojunctions with inhomogeneous barrier heights due to the presence of mixed-phase cocatalysts. The effective barrier heights reached up to 0.8 eV with optimized MoS2 thicknesses, leading to a 670 mV photovoltage enhancement without employing buried Si p-n junctions. The fast-transient behaviors via light illumination show that the mixed-phase layered chalcogenides can serve as efficient cocatalysts by depinning the Fermi levels at the interfaces. A long-term operation of ~ 70 h was also demonstrated in a 0.5 M H2SO4 solution.

Excitotoxicity related to the dysfunction of the N-methyl-d-aspartate receptor (NMDAR) has been indicated to play an integral role in the pathophysiology of multiple disease states, including neurodegenerative disorders such as Parkinson’s disease. There is a notable gap in the market for novel NMDAR antagonists, however current methods to analyze potential antagonists rely on indirect measurements of calcium flux and hazardous radioligand binding assays. Recently, a fluorescent NMDAR ligand, N-adamantan-1-yl-dimethylamino-1-naphthalenesulfonic acid, known as AM-DAN was developed by our group. Additional studies on this ligand is necessary to evaluate its potential as a biological tool in NMDAR research. Therefore, this study was aimed at conducting structural analyses, fluorescence experiments, high-accuracy NMDAR molecular modelling and NMDAR phencyclidine (PCP) site competition binding studies using AM-DAN. Results revealed that AM-DAN has appropriate structural properties, significant fluorescent ability in various solvents and is able to bind selectively and compete for the PCP-binding site of the NMDAR. Therefore, AM-DAN holds promise as a novel fluorescent ligand to measure the affinity of prospective drugs binding at the NMDAR PCP-site and may circumvent the use of radioligands.

Taste signaling is a complex process that is linked to obesity and its associated metabolic syndromes. The sweet taste is mediated through a heterodimeric G protein coupled receptor (GPRC) in a species-specific manner and at multi-tissue specific levels. The sweet receptor recognizes a large number of ligands with structural and functional diversities to modulate different amplitudes of downstream signaling pathway(s). The human sweet-taste receptor has been extremely difficult to study by biophysical methods due to inadequate methods for producing large homogeneous quantities of the taste-receptor protein and a lack of reliable in vitro assays to precisely measure productive ligand binding modes leading to activity upon their interactions with the receptor protein. We report a multimodal high throughput assays to monitor ligand binding, receptor stability and conformational changes to model the molecular interactions between ligand-receptor. We applied saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR) complemented by differential scanning calorimetry (DSC), circular dichroism (CD) spectroscopy, and intrinsic fluorescence spectroscopy (IF) to characterize binding interactions. Our method using complementary NMR and biophysical analysis is advantageous to study the mechanism of ligand binding and signaling processes in other GPCRs.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Controlling water and food contamination by pathogenic organisms requires quick, simple, and low-cost methods. using affinity between mannose and type I fimbriae in the cell wall of Escherichia coli bacteria as evaluation elements compared to the conventional plate counting technique enables a reliable sensing platform for the detection of bacteria. In this study, a simple new sensor based on electrochemical impedance spectroscopy (EIS) for rapid and sensitive detection of Escherichia coli was developed. Biorecognition layer of the sensor was formed by covalent attachment of p-carboxyphenylamino mannose (PCAM) to gold nanoparticles (AuNPs) electrodeposited on the surface of glassy carbon electrode (GCE). The resultant structure of PCAM was characterized and confirmed using FTIR. The developed biosensor demonstrated a linear response with a logarithm of bacterial concentration (R2 = 0.998) in the range of 1.3 × 10 1~ 1.3 × 106 CFU.mL−1with the limit of detection of 2 CFU.mL−1 within 60 min. The sensor did not generate any significant signals with two non-target strains, demonstrating high selectivity of the developed biorecognition chemistry. Selectivity of the sensor and its applicability to analysis of the real samples was investigated in samples of tap water. Overall, the developed sensor has shown to be promising for the detection of E. coli pathogen in water due to its high sensitivity, short detection time, low cost, high specificity, and user-friendliness.

Studies shows that, normal to high serum 25(OH)D status appears to have some beneficial influence on the incidence and severity of some, though not all, types of infections. However, studies with vitamin D supplementation on young children produced conflicting results with respect to the level of vitamin D deficiency among common medical illnesses among children. Method: A systematic review of literatures from PubMed, CINAHL, Web of science, global health and Google scholar electronic databases was conducted to assess the pooled prevalence of vitamin D deficiency among healthy and sick children in sub-Saharan Africa. The data was extracted by two authors independently using standard data extraction format and STATA Version 14 was used for analysis. The heterogeneity of the studies was assessed by using I2 test. A random-effects model was used to estimate the pooled prevalence among both healthy and sick children. Presence of publication bias was checked using Funnel plot and Egger's test. Result: A total of 1212 articles were identified by the total search of utilized data bases of which 13 papers fulfilled the inclusion criteria and accessible with full document. The meta-analysis revealed that the pooled prevalence of vitamin D deficiency among healthy children in this study was 50.06% (95%CI 33.46%, 66.67%) with mean serum vitamin D level of 41.06 nm/L (CI range from 23.82nm/L to 58.31nm/L). The pooled prevalence among the sick children was 39.36% (CI 20.57%, 57.96%) with 66.96nm/L (95% CI 54.81nm/L, 79.11nm/L) mean concentration of vitamin D. Comparing the two level of the pooled prevalence, the prevalence among the healthy children was significantly higher compared to those who have common medical illnesses and the pooled mean concentration among the sick was much higher than the mean concentration among healthy children. Conclusion: The level of pooled prevalence among both group of population was significantly of public health concern and the prevalence among the healthy children was much higher among the sick children implying the need for reconsideration of available recommendations for the prevention of vitamin D deficiency

Four models of Ce(III) complexes with four ligands based on a 1,2,3-triazole derivatives were studied at four DFT levels. The effect of different ligands on the atomic charge value on the cerium ion was analyzed. Several relationships were clearly established between this atomic charge and that of the surrounding atoms, as well as with several geometric parameters of the ligand and with the molecular properties of the Ce(III) complex. The experimental IR and Raman spectra of the newly obtained Ce(III) complex with the (pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylate ligand were interpreted based on their comparison to the theoretical scaled ones using the scaling equations determined by two procedures and four DFT levels. Therefore, the structure predicted for the synthesized Ce(III) complex was clearly characterized and confirmed. The potential antioxidant action of Ce(III) complex was elucidated and compared with other Ln(III) complexes in order to find out the differences in their biological activity profiles.

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

Human NAD(P)H:quinone oxidoreductase 1 (NQO1) is a multi-functional protein whose alteration is associated with cancer, Parkinson´s and Alzheimer´s diseases. NQO1 displays a remarkable functional chemistry, capable of binding different functional ligands that modulate its activity, stability and interaction with proteins and nucleic acids. Our understanding on this functional chemistry is limited by the difficulty of obtaining structural and dynamic information on many of these states. Herein, we have used hydrogen/deuterium exchange monitored by mass-spectrometry (HDXMS) to investigate the structural dynamics of NQO1 in three ligation states: without ligands (NQO1apo), with FAD (NQO1holo) and with FAD and the inhibitor dicoumarol (NQO1dic). We show that NQO1apo has a minimally stable folded core holding the protein dimer and with FAD and dicoumarol ligand binding sites populating binding non-competent conformations. Binding of FAD significantly decreases protein dynamics and stabilizes the FAD and dicoumarol binding sites as well as the monomer:monomer interface. Dicoumarol binding further stabilizes all three functional sites, a result not previously anticipated by available crystallographic models. Our work provides an experimental perspective into the communication of stability effects through the NQO1 dimer, valuable to understand at the molecular level the effects of disease-associated variants, post-translation modifications and ligand binding cooperativity in NQO1.

D-Serine, a co-agonist of NMDA receptors has sparked a contentious debate within the scientific community regarding its status as a gliotransmitter or a neurotransmitter. This comprehensive review delves into the heart of this debate, offering a meticulous analysis of the existing evidence from various research methodologies. Immunostaining studies and cell-selective mutations provide compelling support for D-serine's neuronal origin, bolstering the serine shuttle model. In contrast, the gliotransmission hypothesis, proposing astrocytic synthesis and release, faces critical scrutiny as inconsistencies in supporting data emerge. In vivo microdialysis experiments unveil a neuronal contribution to D-serine release and its profound impact on synaptic plasticity, further strengthening the case for neuronal dominance. Counterarguments in favor of astrocytic D-serine release are systematically dissected, revealing inherent limitations and ambiguities. Collectively, the evidence corroborates D-serine's neuronal source and discounts the astrocytic hypothesis. This review underscores the need for scientific rigor when evaluating contentious topics and affirms the simplicity of the neuronal explanation, aligning D-serine with the serine shuttle model, thus advancing our comprehension of its pivotal role in synaptic function and cognitive processes. As the debate continues to evolve, this exploration encourages ongoing research to unravel the intricate mechanisms governing D-serine neurotransmission.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

The InSAR technique measures the displacement of an indicator using SAR image interference. The technique of interfering two SAR images among InSAR techniques is called Differential InSAR (D-InSAR). In the process of D-InSAR, the filtering technique is used in the Unwrapped Mask, usually using the GoldStein method. However, since the Goldstein method removes the noise on the path, it is difficult to derive the displacement value in the agricultural area where the relative coherence is low. In Korea, more than 50% of the whole country consists of mountainous regions and agricultural regions, so it is difficult to use the Goldstein technique polysynthetically. In this study, we set the test-bed for the urban area and the agricultural area based on Coherence, and introduce Goldstein and Boxcar Filter, one of the Goldstein and LSM techniques. Through this process, we want to draw the conclusion which is displacement values ​​in the agricultural area.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p<0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

Chronic oxidative stress in long-distance runners adversely affects conditioning. Therefore, it is important to objectively assess and monitor oxidative stress but measuring oxidative stress can be invasive or require skill to measure. Therefore, this study aimed to verify whether skin autofluorescence (SAF), a noninvasive, rapid, and easily calculable metric for calculating advanced glycation end products (AGEs), is useful as an oxidative stress biomarker. The subjects were 50 young Japanese male long-distance runners (aged 20.2 ± 1.2 years); 35 average male university students (aged 19.8 ± 1.1 years) served as controls. The interactions and relationships between SAF and plasma pentosidine and oxidative stress markers (reactive oxygen metabolite-derived compounds [d-ROMs], biological antioxidant potential [BAP], and the BAP/d-ROMs ratio) in runners were examined, and SAF in the runners and controls was compared. The results suggest that plasma pentosidine in runners is associated with oxidative stress markers and that plasma pentosidine can assess oxidative stress. However, SAF was not validated as an oxidative stress marker because it was not associated with oxidative stress marker. In future, clarifying the factors affecting SAF may clarify the relationship between SAF, plasma pentosidine, and oxidative stress markers.

We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGF stimulated global fibrin matrix contraction (P < 0.005), however cell and matrix patterning were different. We found that during PDGF BB induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (P < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (P < 0.001). Taken together, our results show that cell-induced ECM reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery.

With the advent of COVID19, the attitude of health authorities around the world, led mainly by the West, demanded a level of proof as evidence for cheap, non-patented remedies while promoting expensive, patented, and untested remedies by using emergency use authorization and special provisions afforded to the status of a pandemic emergency. Western science has neither a tested nor a valid historical basis of a logical system that informs to authenticate scientific practices. Here we use a logical heuristic derived from ancient Buddhist logic, which is consistent with the conduct of modern science. We applied the heuristic to show that enough evidence was available for using cost-effective early therapies such as vitamin D supplementation as a public health measure during the first half of 2020. Strong supporting evidence has since accumulated. Apart from political and financial decisions incompatible with science and other conflicts of interest, a critical barrier to evaluating and approving early therapies appears to be the fallacy that the randomized controlled trial (RCT) is the superior proof method in medical hypotheses, including those for nutrients. Logically, no reason exists why properly designed retrospective, ecological, and naturalistic studies with adequate sample sizes and applied appropriate statistical methods would not be as valid as RCTs, especially when elucidating a causative factor instead of treatment. That assertion is particularly true for nutrient deficiencies, interventions, and other cost-effective therapies. Leading health authorities’ failure or refusal to consider other study types (because of either poor logic or vested interest) probably contributed to the spread of misinformation, symptomatic disease, complications, and deaths from COVID19. Partial immunity derived from vaccines and the later development of more contagious variants—and thus a sense of acceptance that SARS-CoV-2 had progressed from a pandemic to an endemic—shows the hollowness of the initial promotions and mandates of vaccines as a cure. Adequate knowledge was available in 2020 to advise that SARS-CoV-2 will continue to mutate, with variants emerging a few times per year, making the vaccine less effective. Emerging evidence confirms that natural immunity better protects against new variants than vaccination against the spike protein. Had vitamin D been adopted as part of the public health measure through a broader supplementation program in 2020 or even today (through sun exposure or as a prophylactic or adjunct therapy early on), the viral spread and symptomatic disease may have been suppressed, with minimal lockdowns and quarantine, and economic harm. The pandemic could have been halted with a significantly reduced need for hospitalization, complications, and deaths, potentially saving millions of lives.

In this paper, we propose a system of nonlinear mixed variational inequality problems, which consists of two elliptic mixed variational inequality problems on Banach spaces. Under suitable assumptions, using the Kakutani-Ky Fan fixed point theorem and Minty techniques, we prove the solution set to the system of nonlinear mixed variational inequality problem is nonempty, weakly compact and unique. Additionally, we suggest a stability result for the system of nonlinear mixed variational inequality problem by perturbing the duality mappings. Furthermore, we present an optimal control problem governed by the system of nonlinear mixed variational inequality problems and establish a solvability result.

Due to the high temperature limitation associated with silicon, SiC, Si₃N₄, TiC, TiN, TiB₂, cBN, CNx, SiO₂, Al₂O₃ and novel multicomponent nanocomposites polymer derived ceramics (PDC) based thin films like Si-C-N, Ti-Si-B-C-N and Si-O-CN that are compatible with silicon and have a wider range of operation in ambient conditions are being investigated. Apart from small scale electro-mechanical devices like N/MEMS, sensors, areas like metallurgical protection, water purification, energy storage, bio medical implants and aerospace have been benefited. The cross-sectional study involving the role of oxygen and nitrogen dissolution at different interfacial configurations has been presented.

This study develops a new definition of fractional derivative that mixes the definitions of fractional derivatives with singular and non-singular kernels. Such developed definition encompasses many types of fractional derivatives, such as the Riemann-Liouville and Caputo fractional derivatives for singular kernel type as well as the Caputo-Fabrizio, the Atangana-Baleanu and the generalized Hattaf fractional derivatives for non-singular kernel type. The associate fractional integral of the new mixed fractional derivative is rigorously introduced. Furthermore, newly numerical scheme is developed to approximate the solutions of a class of fractional differential equations (FDEs) involving the mixed fractional derivative. Finally, an application to computational biology is presented.

Brugada Syndrome is a cardiac channelopathy closely related to lethal arrhythmias and sudden death in people without underlying structural pathology. The diagnosis is usually assumed with electrocardiographic patterns strictly limited to the right precordial leads, V1 or V2; but this is not so at all. In our article, we describe the clinical case of a patient with a novel and different electrocardiographic presentation: the typical diagnostic pattern was presented in a lower lead of the electrocardiogram, and next to it, another pattern was presented in a contiguous lead. In addition, we propose the possible association of a structural pathology (non-compaction cardiomyopathy) with Brugada Syndrome, since both share a possible common genetic origin in the SCN5A gene.

Intranasal (i.n.) administration became an alternative strategy to bypass the blood-brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions and thus, they could be beneficial in the treatment of different medical conditions.

Speech signals are degraded in real-life environments, product of background noise or other factors. The processing of such signals for voice recognition and voice analysis systems presents important challenges. One of the conditions that make adverse quality difficult to handle in those systems is reverberation, produced by sound wave reflections that travel from the source to the microphone in multiple directions.To enhance signals in such adverse conditions, several deep learning-based methods have been proposed and proven to be effective. Recently, recurrent neural networks, especially those with long and short-term memory (LSTM), have presented surprising results in tasks related to time-dependent processing of signals, such as speech. One of the most challenging aspects of LSTM networks is the high computational cost of the training procedure, which has limited extended experimentation in several cases. In this work, we present a proposal to evaluate the hybrid models of neural networks to learn different reverberation conditions without any previous information. The results show that some combination of LSTM and perceptron layers produce good results in comparison to those from pure LSTM networks, given a fixed number of layers. The evaluation has been made based on quality measurements of the signal's spectrum, training time of the networks and statistical validation of results. Results help to affirm the fact that hybrid networks represent an important solution for speech signal enhancement, with advantages in efficiency, but without a significan drop in quality.

In this work, an algorithm for the scheduling of household appliances to reduce the energy cost and the peak-power consumption is proposed. The system architecture of a home energy management system (HEMS) is presented to operate the appliances. The dynamics of thermal and non-thermal appliances is represented into state-space model to formulate the scheduling task into a mixed-integer-linear-programming (MILP) optimization problem. Model predictive control (MPC) strategy is used to operate the appliances in real-time. The HEMS schedules the appliances in a dynamic manner without any a priori knowledge of the load-consumption pattern. At the same time, HEMS responds to the real-time electricity market and the external environmental conditions (solar radiation, ambient temperature etc). Simulation results exhibit the benefits of proposed HEMS by showing the reduction of up to 47% in electricity cost and up to 48% in peak power consumption.

Passive balancing is a traditional choice for lithium-ion battery packs although it is regarded as highly inefficient. One opportunity to improve traditional balancing in sub-medium size battery packs is to combine two balancing methods: passive and active. Statistical analysis have been performed to rationalize battery pack division in smaller packs and use of higher level selective charging method to decrease losses of passive balancing. An experimental balancing prototype have been designed and tested for efficiency. Results indicate energy performance degradation if cells of the pack are with low capacity variation. Proposed balancing approach could improve performance under high cell mismatch conditions.

The review analyzes the studies published mainly in the last 10-15 years, on the synthesis, structure, and sensor properties of semiconductor nanocomposites. Particular attention is paid to the interaction between nanoparticles of the sensitive layer and its effect on the structure, sensitivity, and selectivity of semiconductor sensor systems. Various mechanisms are considered of interaction between nanoparticles in metal oxide composites including incorporation of metal ions of one component into the structure of another, heterocontacts between different nanoparticles, and core-shell systems, as well as their influence on the characteristics of gas sensors. The experimental data and studies on the modeling of charge distribution in semiconductor nanoparticles, which determine the conductivity and sensor effect in one- and two-component systems, are also discussed. It is shown that the model which considers the interactions of nanoparticles best describes the experimental results. Some mechanisms of detection selectivity are considered in the conclusion.

Economic expedience of waste heat recovery systems (WHRS), especially for low temperature difference applications, is often questionable due to high capital investments and long pay-back periods. By its simple design isobaric expansion (IE) machines could provide a viable pathway to utilize otherwise unprofitable waste heat streams for power generation and particularly for pumping liquids and compression of gases. Different engine configurations are presented and discussed. A new method of modelling and calculation of the IE process and efficiency is used on IE cycles with various pure and mixtures as a working fluid. Some interesting cases are presented. It is shown in this paper, that the simplest non-regenerative IE engines are efficient at low temperature differences between a heat source and heat sink. Efficiency of non-regenerative IE process with pure working fluid can be very high approaching Carnot efficiency at low pressure and heat source/heat sink temperature differences. Regeneration permits to increase efficiency of the IE-cycle to some extent. Application of mixed working fluids in combination with regeneration permits to significantly increase the range of high efficiencies to much larger temperature and pressure differences.

Tree biomass and diversity relationship in mixed forest impacts on forest ecosystem services provisions. Tree biomass yield is driven by several aspects such as species identity, site condition, stand density, tree age as well as tree diversity expressed as species mingling and structural diversity. By comparing diverse degrees of tree mixture in natural forests we can insight on the ecosystem services provision level and dynamic. Two monitoring sites in the Castilian Northern Plateau (Spain) have been analyzed to disentangle the relationships between biodiversity levels and tree biomass yield. Two permanent one ha squared plots were established at Llano de San Marugan and Valdepoza. In each plot all individual trees were measured (diameter and height), georeferenced and its species identity defined. Tree species in the two sites were Pinus sylvestris, Pinus nigra, Pinus pinea, Quercus pyrenaica, Quercus ilex, Quercus faginea and Juniperus thurifera. From these datasets ten diversity indices that fall in three categories (species richness indices, species compositional/mingling indices and vertical structural indices) were used as predictor variables to fit several candidate models. By merging the trees by site (without considering the species identity) selected models include individual tree basal area as explanatory variable combining by addition or interaction with diversity indices. When species are analyzed independently structural diversity impacts on biomass yield in combination (additive or multiplicative) with tree size is negative Pinus nigra and positive for the other species.

Monitoring volatile organic compounds (VOCs) places a crucial role in environmental pollutants control and indoor air quality. In this study, a metal-oxide (MOx) sensor detector (used in a commercially available monitor) was employed to delineate the composition of air containing three common VOCs (ethanol, acetone and hexane) under various concentrations. Experiments with a single component and double components were conducted to investigate how the solvents interact with the metal oxide sensor. The experimental results revealed that the affinity between VOC and sensor was in the following order: acetone > ethanol > n-hexane. A mathematical model was developed, based on the experimental findings and data analysis, to convert the output resistance value of the sensor into concentration values, which in turn can be used to calculate a VOC-based air quality index. Empirical equations were established based on inferences of vapor composition versus resistance trends, and on an approach of using original and diluted air samples to generate two sets of resistance data per sample. The calibration of numerous model parameters allowed matching simulated curves to measured data. As such, the predictive mathematical model enabled quantifying not only the total concentration of sensed VOCs, but also estimating the VOC composition. This first attempt to obtain semi-quantitative data from a single MOx sensor, despite remaining selectivity challenges, is aimed at expanding the capability of mobile air pollutants monitoring devices.

Mixed reality technology is being increasingly used in cultural heritage attractions to enhance visitors’ experience. However, how the characteristics of mixed reality affect satisfaction and brand loyalty has not been explored in previous research. The purpose of this study is to identify factors affecting satisfaction with mixed reality experiences at cultural and artistic visitor attractions and their influence on brand loyalty, which is connected with management performance. We propose a theoretical model based on brand equity theory in the context of mixed reality experience. Survey data were gathered from 251 respondents visiting a cultural and artistic visitor attraction in Seoul, Korea using a stratified sampling method. PLS-SEM was employed for the data analysis. The results suggest that the characteristics of mixed reality (interactivity, vividness) not only influence the affective aspects (perceived immersion, perceived enjoyment) of visitors’ experience, but also positively affect brand awareness, brand association, and brand loyalty.

Linear mixed models are frequently used for analysing heterogeneous data in a broad range of applications. The restricted maximum likelihood method is often preferred to estimate co-variance parameters in such models due to its unbiased estimation of the underlying variance parameters. The restricted log-likelihood function involves log determinants of a complicated co-variance matrix. An efficient statistical estimate of the underlying model parameters and quantifying the accuracy of the estimation requires the first derivatives and the second derivatives of the restricted log-likelihood function, i.e., the observed information. Standard approaches to compute the observed information and its expectation, the Fisher information, is computationally prohibitive for linear mixed models with thousands random and fixed effects. Customized algorithms are of highly demand to keep mixed models analysis scalable for increasing high-throughput heterogeneous data sets. In this paper, we explore how to leverage an averaged information splitting technique and dedicate matrix transform to significantly reduce computations and to accelerate computing. Together with a fill-in reducing multi-frontal sparse direct solver, the averaged information splitting approach improves the performance of the computation process.

This paper introduces PatchFusion, an innovative approach for nonrigid tracking and reconstruction of deformable objects using a single RGB-D sensor. Existing methods face challenges in accurately capturing the rapid deformations of soft and flexible objects, thereby limiting their utility in diverse scenarios. Our approach overcomes this challenge by employing a dynamic patch-based framework that adapts to rapid inter-frame motions. Firstly, patch-wise rigid transformation fields for non-overlapping patches are solved via Iterative Closest Point (ICP) by incorporating geometric features as additional similarity constraints, thereby enhancing robustness and accuracy. Secondly, deformation optimization based on a nonrigid solver is applied to refine the coarse transformation fields. In order to enable simultaneous tracking and reconstruction of deformable objects, the patch-based rigid solver is designed to run in parallel with the nonrigid solver, serving as a plug-and-play module requiring minimal modifications for integration while enabling real-time performance. Following a comprehensive evaluation, PatchFusion showcases superior performance in effectively dealing with rapid inter-frame deformations when compared to existing techniques, rendering it a promising solution with broad applicability across domains such as robotics, computer vision, and human-computer interaction.

This review examines the challenges faced by the pig industry, with a specific emphasis on improving the health and growth of weaned pigs. It emphasises the immediate necessity of investigating alternative approaches to managing pig nutrition and health due to restrictions on the use of antibiotics and the prohibition of zinc oxide in weaned pig diets. The weaning phase is identified as a critical stage in piglet development, characterized by stressors that affect their gastrointestinal health, immune responses, and overall physiology. The primary challenge during weaning arises from transitioning piglets from a digestible milk-based diet to a less digestible cereal-based feed, causing nutritional stress. This manifests as reduced feed intake, leading to gastrointestinal disturbances, intestinal inflammation, and adverse effects on intestinal structure and microbiota. To address these challenges and optimise piglet development, various nutritional strategies have been explored. Notably, glucans, particularly β-glucans from fungi, cereals, algae, and yeast, show promise in alleviating weaning-related issues. Furthermore, it's important to highlight the critical roles played by vitamin D and selenium in piglet nutrition. These essential nutrients can be sourced naturally from enriched mushrooms that are specifically enriched with vitamin D and selenium, providing a valuable dietary option. In conclusion, effective nutritional strategies, including glucans, vitamin D, selenium, and enriched mushrooms, are beneficial for addressing weaning-related challenges.

Under the guidance of our previous achievements, and in order to extend this small molecular library. In current work, other 21 novel structures of thieno[2,3-d]pyrimidines containing isoxazole-moiety (1a-1u) were firstly synthesized and the cytotoxicity to A549, HCT116 and MCF-7 cell lines was evaluated using the MTT method. The results showed that most target compounds exhibited good to excellent cytotoxicity to A549, HCT116 and MCF-7 cell lines, especially 6-Methyl-4-{[3-(4-chlorophenyl)-isoxazol-5-yl-]-methoxy-}-thieno[2,3-d]-pyrimidine (1e) exhibited a broad-spectrum and the most potent cytotoxicity to A549, HCT116 and MCF-7 cell lines (IC50s: 2.79, 6.69 and 4.21×10^-3 μM, respectively) as compared with the reference drug gefitinib (IC50s: 17.90, 21.55 and 20.68 μM, respectively). 1e can be seen as the best drug candidates for development of anticancer drugs.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

Arguments of Mises and Hayek, who opposed the planned economy (PE), are used in the paper as a starting point for establishing the objective area of effective application of the PE. The abstract model of PE, based on the definitions of Mises and Hayek, leads to the conclusion that for the effective use of PE, it must be a part of mixed economy and it must produce a limited amount of essential goods of irreducible demand. These goods must be distributed among all members of society free of charge, evenly, without competition. Examples of a mixed economy are given that meet this requirement. Calculations of the personal benefit in the transition to a mixed model of the economy have been carried out. The positive and negative qualities of the planned and market methods of organization are considered. Mixed economy model combines these qualities in optimal construction. An analytical framework has been introduced for the construction of product characterization curves. Such curves provide criteria for determining the efficiency of manufacturing of this product in a planned economy. The general economic prerequisites for the usability of the PE are clarified. The applicability and advantages of the PE for the organization of the universal basic income (UBI) system are demonstrated. The possibility of using PE to solve the problem of guaranteed employment is mentioned.

A custom-designed series of unsymmetrical spiroalkanedithiols having tailgroups comprised of a terminally fluorinated chain and a hydrocarbon chain of varying lengths were synthesized and used to prepare self-assembled monolayers (SAMs) on gold substrates. The specific structure of the adsorbates was of the form [CH₃(CH₂)_n][CF₃(CF₂)₇(CH₂)₈]C[CH₂SH]₂, where n = 7, 9, and 12 (designated as F8H10-C10, F8H10-C12, and F8H10-C18, respectively). The influence of the length of the hydrocarbon chain in the bidentate dithiol on the structure and interfacial properties of the monolayer was explored. A structurally analogous partially fluorinated monodentate alkanethiol and the corresponding normal alkanethiols were used to generate appropriate SAMs as reference systems. Ellipsometric thickness measurements showed an unexpectedly low film thickness for the SAMs derived from the bidentate adsorbates, possibly due to disruptions in interchain packing caused by the fluorocarbon chains (i.e., phase-incompatible fluorocarbon-hydrocarbon interactions), ultimately giving rise to loosely packed and disordered films. Analysis by X-ray photoelectron spectroscopy (XPS) were also consistent with a model in which the films were loosely packed; additionally, the XPS spectra confirmed the attachment of the sulfur headgroups of the bidentate adsorbates onto the gold substrates. Studies of the SAMs by polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS) suggested that as the length of the hydrocarbon chain in the adsorbates was extended, a more ordered surface was achieved by reducing the tilt of the fluorocarbon segment. The wettability data indicated that the adsorbates with longer alkyl chains were less wettable than those with shorter alkyl chains, likely due to an increase in interchain van der Waals forces in the former.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

Though Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D was never unveiled so far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB231 and MCF7 cells. Also, Moracin D increased sub G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of pro-cysteine aspartyl-specific protease (procaspase 3), c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2),and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK 3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3 and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspase and GSK3β

Coronavirus Disease 2019 (COVID-19) exhibits a significant variation in presentation of symptoms ranging from mild to severe life-threatening symptoms, including death. COVID-19 infection susceptibility has been linked with various covariates, but studies in Qatar are limited. Data from Qatar Biobank (QBB) (n = 10,000; 18- to 79-year-old adults) were analyzed for associations between sociodemographic and lifestyle factors and susceptibility to COVID-19. Logistic regression was used to assess the associations between COVID-19 and age, gender, body mass index (BMI), smoking status, education level, dietary patterns, supplement use, physical activity, history of bariatric surgery, diabetes, and hypertension. In total, 10.5% (n = 1045) of the participants had COVID-19. Compared to non-smokers, current and ex-smokers had lower odds of having COVID-19 (odds ratio [OR]= 0.55; 95% CI: 0.44-0.68 and OR= 0.70; 95% CI: 0.57-0.86, respectively). Vitamin D supplement use was associated with an 18% reduction of the likelihood of contracting COVID-19 (OR = 0.82; 95% CI: 0.69-0.97). Obesity (BMI ≥30 kg/m2), history of bariatric surgery and higher adherence to the modern dietary pattern– characterized by consumption of foods high in saturated fat and refined carbohydrates– were positively associated with COVID-19. Our findings indicate that adopting a healthy lifestyle may be helpful in the prevention of COVID-19 infection.

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analysed its oral pharmacokinetics and its effects on a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), b) insulin signaling in the liver and c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associate with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation while sustaining glycaemia through liver-based mechanisms of glycolysis control.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A-D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A-D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The investigation involves the utilization of molecular modeling and computational chemistry tools, with a specific focus on Conceptual DFT. These techniques are applied to examine the chemical reactivity of Talarolide A and Talaropeptides A-D, shedding light on their potential for interacting with various biological targets. The research reveals insights into the chemical reactivity of Talarolide A and Talaropeptides A-D, uncovering active reaction sites and potential biological targets. Talarolide A demonstrates robust anti-inflammatory properties and antitumor activity against diverse cancer cell lines, while Talaropeptide A displays antimicrobial efficacy against both bacteria and fungi. The study underscores the significance of comprehending the chemical reactivity of natural marine products for advancing pharmaceutical development. By employing computational tools such as Conceptual DFT, this research uncovers crucial information about the active sites and potential targets of Talarolide A and Talaropeptides A-D. The findings contribute to the broader understanding of marine-derived peptides and their prospects as pharmaceutical agents, though further investigations are necessary to fully elucidate their pharmacological attributes.

Microencapsulation by atomization can be used to minimize the loss of bioactive compounds, improving the characteristics and applicability of the powdered product. This study evaluates the effect of different encapsulating agents (maltodextrin, gum arabic, and chitosan) and three spray nozzle diameters (1.0, 1.2, and 1.5 mm) on the atomization of guavira (Campomanesia adamantium) pulp with added 6% bocaiuva (Acrocomia aculeata) dehydrated pulp in the green maturation stage. The experiment followed a simplex-centroid mixed design, with carrier agent concentrations and spray nozzle diameters as independent variables and powder yield, solubility, hygroscopicity, and vitamin C content as dependent variables. The results show that gum arabica increased powder yield and vitamin C retention. The addition of maltodextrin resulted in powders with increased solubility and low hygroscopicity. Furthermore, the optimization tool indicated that the best process conditions were achieved with the addition of gum arabic (10.8%) and chitosan (7.2%), resulting in powders with 29.48% yield, 82.96% solubility, 15.90% hygroscopicity and 741.11 mg/100g vitamin C. Furthermore, the 1.0 mm diameter spray nozzle was considered the most suitable for obtaining guavira pulp microparticles with higher ascorbic acid content.

Reactions of N‚N'-bis(3-methylpyridyl)oxalamide (L1), N,N’-bis(3-methylpyridyl)adipoamide (L2) and N,N’-bis(3-methylpyridyl)sebacoamide (L3) with tricarboxylic acids and Cu(II) salts afforded {[Cu(L1)(1,3,5-HBTC)]·H2O}n (1,3,5-H3BTC = 1,3,5-benzenetricarboxylic acid), 1, {[Cu1.5(L2)1.5(1,3,5-BTC)(H2O)2]·6.5H2O}n, 2, [Cu(L2)0.5(1,3,5-HBTB)]n (1,3,5-H3BTB = 1,3,5-tri(4-carboxyphenyl)benzene), 3, [Cu4(L3)(OH)2(1,3,5-BTC)2]n, 4, {[Cu3(L3)2(1,3,5-BTB)2]·2.5MeOH·2H2O}n, 5, and {[Cu3(L3)2(1,3,5-BTB)2 ]·DMF·2H2O}n, 6, which have been structurally characterized by using single crystal X-ray crystallography. Complexes 1 – 4 form a 2D layer with the {44.62}-sql topology, a 2D layer with the (4.62)2(42.62.82)-bex topology, a 3-fold interpenetrated 3D net with the (412.63)-pcu topology and a 3D framework with the (410.632.83)(42.6)2(43.63) topology, respectively, whereas 5 and 6 are 3D frameworks with the (63)2(64.82)(68.85.102) topology. Complex 5 shows a better iodine-adsorption factor of 290.0 mg g-1 at 60 oC for 360 minutes than the other ones, revealing that the flexibility of the spacer ligand governs the structural diversity and the adsorption capacity.

Vanadium(IV) chalcogenide materials are of increasing interest for use in catalysis and energy conversion-related applications. Since no ternary compounds are yet known in the V–Se–Te system, we studied ternary VwSeyTe2–y (w = 1.10, 1.13; y = 0.42, 0.72) phases crystallizing in space group P3m1 (no. 164). Two single-crystal specimens with differing compositions of a solid solution were obtained using the ceramic method. All products were characterized by either single-crystal or powder X-ray diffraction. The lattice parameters increase with rising tellurium content in accordance to the larger ionic radius of the tellurium anion compared to selenium. The chemical compositions were confirmed by energy dispersive X-ray spectroscopy. Further, magnetic measurements revealed mostly antiferromagnetic properties. Simultaneous differential scanning calorimetry/thermogravimetric analyses in nitrogen atmosphere showed endothermic decomposition accompanied by the formation of VN. The results of this work can serve as a basis for the synthesis of new phases in the V–Se–Te and related vanadium chalcogenide systems.

A single-crystal of ytterbium-doped “mixed” yttrium-lutetium aluminium garnet with a stoichiometric composition of (Y0.601Lu0.233Yb0.166)3Al5O12 was grown by the Czochralski method and its structure, vibronic, spectroscopic and laser properties were studied. The stimulated-emission cross-section for Yb3+ ions was maximized to 2.53×10-20 cm2 at 1031 nm, the emission bandwidth is ~8 nm and the reabsorption-free luminescence lifetime of the 2F5/2 state is 1.063 ms. Pumped at 941 nm, the Yb-laser generated a maximum output power of 1.04 W at 1.03 and 1.05 μm with a high slope efficiency of 76.4% and a laser threshold of 76 mW. A continuous wavelength tuning over a range of 51.6 nm (1026.4 - 1078.0 nm) was also achieved. Power scaling is achieved using a 969 nm-diode pumped microchip cavity. A maximum output power of ~9 W is obtained at 1.05 μm with a slope efficiency of 76% and with an almost circular laser beam profile.

The increasing enrollments in the English Departments at Palestinian universities highlight the need to understand the attitudes and expectations of students, as these factors can significantly impact their motivation and proficiency in learning English as a foreign language (EFL). This study aimed to explore the attitudes and expectations of Palestinian first-year English majors in relation to EFL learning. A total of 244 students participated in the study, completing a questionnaire and participating in interviews to provide a comprehensive understanding of their perspectives. The results revealed a high level of enthusiasm among the students towards EFL, as evidenced by their strong attitudes and exceptionally high expectations. Moreover, the study identified specific student characteristics, including gender and the required hours dedicated to English learning, as well as the experience of studying abroad, which served as predictive factors for their attitudes and expectations. The findings emphasize the importance of regularly assessing the attitudes and expectations of learners in English departments to effectively cater to their needs and attract more students. By understanding the motivating factors and aligning instructional strategies accordingly, English departments can create a more engaging and tailored learning environment for students pursuing English as a foreign language.

The COVID-19 pandemic affects all parameters, especially health care professionals, drugs and medical supplies. The KERRA is a mixed medicinal plant capsule that is used for the treatment of patients with high fever with food and drug administration approved by FDA Thailand. Recently, KERRA showed quicker recovery for COVID-19 patients. Therefore, it is possible that some ingredients in KERRA could inhibit SARS-CoV-2. In this study, two important replication-related enzymes in SARS-CoV-2, a main protease and an RNA-dependent RNA polymerase (RdRp), were used to study the effect of KERRA. The results showed that KERRA inhibited the SARS-CoV-2 main protease and SARS-CoV-2 RdRp with IC50 values of 49.91 ± 1.75 ng/mL and 36.23 ± 5.23 µg/mL, respectively. KERRA displayed no cytotoxic activity on macrophage cells at concentrations lower than 1 mg/mL and exhibited anti-inflammatory activity. Additionally, KERRA was against a feline coronavirus (feline infectious peritonitis [FIP]) infection with an EC50 value of 134.3 g/mL. This study supports the potential use of KERRA as a candidate drug for COVID-19.

In this study, Mg-Al and Mg-Al-Ni - layered double hydroxides (LDHs) were successfully synthesized for efficient removal of Mn²⁺ from synthetically wastewater. LDH adsorbents (Mg-Al and Mg-Ni-Al) were prepared by co-precipitation method. The formation of the layered double hydroxide, the adsorption of manganese on both LDH (Mg-Al and Mg-Ni-Al) were observed by XRD, SEM and EDX analysis. The various parameters such as the effect of shaking time, initial Mn²⁺ concentration, temperature were controlled and optimized to removal of Mn²⁺ from synthetic wastewater. The kinetics and adsorption isotherms for Mn²⁺ removal from wastewater were studied in batch mode. At temperatures of 10 °C and 20 °C the adsorption equilibrium was reached after 24 h. Adsorption isotherms of Mn²⁺ are well fitted by Langmuir and Freundlich isotherm equation. The adsorption capacity of Mn²⁺ from synthetic wastewater of 80.607 mg/kg was obtained for (Mg-Al-Ni)-LDH. It is found that the adsorption kinetics is best described by the pseudo-second order model. These results prove that LDHs can be considered as a potential material for adsorption of Mn²⁺ from wastewater.

Technology advancements are evident in the healthcare field; numerous new opportunities and applications have emerged during the last years based on embedded intelligence and related to real-time diagnosis of medical issues, tele-care and telemedicine, remote monitoring of patients, computer-assisted “smart” transportation in case of emergencies, as well as new types of remotely controlled surgical operations. This paper aims to provide an overview of the application of embedded intelligence in the field of healthcare; it gathers the main critical requirements, related technologies and research advancements up to date, and it presents the most important challenges that are yet to be faced. The main focus is given in the development and optimization of Body Area Networks (BANs) based on advanced embedded sensing devices, the optimization of smart gateways in such networks, and the provision of holistic scalable and secure solutions in the healthcare domain. In addition, the paper presents two principal use cases that stem from the combination of novel information and communication technologies with classic healthcare practices, explaining the functional and non-functional requirements, as well as the mixed criticality characteristics of the associated systems.

In the international scenario of agriculture, Brazil stands out as the main producer and consumer of common bean (Phaseolus vulgaris L.) The increase in the productive potential of the crop is mainly due to breeding programs. The objective of this study was to estimate genetic parameters, predict genotypic values with REML/BLUP (Restricted Maximum Likelihood/Best Linear Unbiased Prediction) and, based on these values, study the variability in common bean cultivars with carioca and black grain. Twenty three agromorphological descriptors were evaluated, among them grain yield. Deviance analysis detected significant differences between the cultivars in both groups. Selective accuracy (Ac) was considered high for most of the traits. Broad-sense heritability (h_g² ) ranged from 0.05 to 0.72, but it was low for the trait yield (YLD). In the carioca grain group, the h_g² values for the traits related to plant morphology were higher than in the black group. Nevertheless, the h_g² values in the black group were higher in relation to the pod and seed traits. The correlations for YLD were moderate but different in the two commercial groups studied. In the black group, variables related to the seed morphology were correlated with grain yield, and in the carioca group, traits related to seed quantity. Based on the groupings, variability among the cultivars was observed. Three distinct clusters were formed for the carioca group and four for the black group. Based on the predicted genetic values, genetic variability and the most adapted and stable cultivars were detected among the cultivars in the studied environments.

Understory plants are important components of forest ecosystem productivity and diversity. Compared to biomass models of overstory canopy trees, few are available for understory saplings and shrubs and therefore their roles in estimation of forest carbon pools are often ignored. In this study, we harvested 24 understory species including 4 saplings, 9 tree-like shrubs and 11 typical shrubs in coniferous and broadleaved mixed forest in northeastern China and developed the best fit allometric equations of above- and below-ground and total biomass by species-specific or multispecies using morphological measurements of basal diameter, height and crown area as independent variables. The result showed that single basal diameter, height or crown area had good explanatory power for both species-specific and multispecies (p<0.001). The best-fit models included only basal diameter in sapling and tree-like shrubs, and combinations of crown area, height, and basal diameter in typical shrubs. The logarithmic model was most desired among the 4 model forms of linear, quadratic, multiple linear and logarithmic, for species-specific and multispecies. The models we developed should help the estimation of forest ecosystem carbon stocks, especially for belowground component, and provide tools for quantification of individual species biomass of understory plants.

The ocean’s mixed layer depth (MLD) plays an important role in understanding climate dynamics, especially during extreme weather occurrences like hurricanes. This study investigates the effects of Hurricane Katrina (2005) on the MLD in the Gulf of Mexico, using the Delft3D modeling system. By integrating hydrodynamics and wave dynamics modules, we simulate the ocean’s response to extreme weather, focusing on temperature, salinity and MLD variations. Our analysis reveals significant cooling and mixing induced by Katrina, resulting in spatial and temporal fluctuations in temperature (~± 4°C) and salinity (~± 2.5 ppt). The MLD is estimated using a simple threshold method, revealing a substantial deepening to ~120 m on August 29th-30th during Hurricane Katrina in the middle of northern Gulf of Mexico, compared to an average MLD of ~20-40 m during pre-storm conditions. It took about 18-days to recover to ~84% of the pre-storm level after Katrina. Compared to the stand-alone FLOW model, the coupled FLOW+WAVE model yields a deeper MLD of ~5%. The MLD recovery and wave effect on the MLD provide insights from various scientific, environmental and operational perspectives, offering a valuable basis for ocean management, planning and applications, particularly during extreme weather events.

Valsartan (Val) is an important antihypertensive medication with side effects such as dizziness and angioedema. These constraints are due to the low oral bioavailability and relatively short half-life. The goal here is to incorporate Val into a mixed micelles system that can enhance transdermal delivery. Thin-film hydration and micro-phase separation were used to produce Val-loaded mixed micelle systems. A variety of factors, including surfactant type and drug-to-surfactant ratio, were optimized to produce micelles with low size and high Val entrapment efficiency (EE). The size, polydispersity index (PDI), zeta-potential, and drug entrapment efficiency of the prepared micelles were all measured. The drug release profiles in vitro were assessed using dialysis bags, and the permeation through abdominal rat skin was assessed using a Franz diffusion cell. All formulations had high EE levels exceeding 90% and low particle charges. The micellar sizes ranged from 107.6 to 191.7nm, with average PDI values of 0.3. The in vitro release demonstrated a uniform slow rate that lasted one week with varying extents. F7 demonstrated a significant (P < 0.01) transdermal efflux of 68.84 ± 3.96 µg/cm2/h through rat skin when compared to the control. As a result, the enhancement factor was 16.57. Val-loaded mixed micelles were successfully prepared using two simple methods with high reproducibility, and extensive transdermal delivery was demonstrated in the absence of any aggressive skin modifying enhancers.

In this work, we propose a transition wave equation from quantum to classical regime in the framework of the von Neumann formalism for ensembles and then obtain an equivalent scaled equation. This leads us to develop a scaled statistical theory following the well-known Wigner-Moyal approach of quantum mechanics. This scaled nonequilibrium statistical mechanics has in it all the ingredients of the classical and quantum theory described in terms of a continuous parameter displaying all the dynamical regimes in-between the two extreme cases. Finally, a simple application of our scaled formalism consisting of reflection from a mirror by computing various quantities including probability density plots, scaled trajectories and arrival times are analyzed.

The article is focused on detailed framework process for hierarchized construction of periodic freight train paths (PFTPs) – allocation of pre-arranged railway capacity to freight rail operators. The framework process considers fluctuations in demand for capacity from freight rail opera-tors, so the quality of a freight train path is related with its construction priority. Introduced framework process aims to offer freight rail operators attractive train paths, with low number of scheduled stops, and this way enhance competitiveness and decrease energy consumption of freight railway as a factor for sustainable development. The proposed generic process is in-tended for all time horizons of capacity allocation. Correctness of the framework process is tested on the example of mainline Prague – Dresden, in the context of prospective (denser) mod-el passenger timetable.

Functional mobility assessments (i.e., Timed Up and Go) are commonly used clinical tools for mobility and fall risk screening in the aging population. In this work, we proposed a new Mixed Reality (MR)-based assessment that utilized a Microsoft HoloLens^TM headset to automatically lead and track the performance of functional mobility tests, and subsequently evaluated its validity in comparison with reference inertial sensors. Twenty-two healthy adults (10 older, 12 young) participated in this study. An automated functional mobility assessment app was developed based on the HoloLens platform. Mobility performance was recorded with the headset built-in sensor and validated with reference inertial sensor (Opal, APDM) taped on the headset and lower back. Results indicate vertical kinematic measures by HoloLens was in good agreement with the reference sensor (Normalized RMSE ~ 10%). Additionally, the HoloLens-based test completion time was in perfect agreement with clinical standard stopwatch measure. Overall, our preliminary investigation indicates that it is possible to use an MR headset to automatically guide users to complete common mobility tests with good measurement accuracy, thus it has great potential to provide objective and efficient sensor-based mobility assessment.

The use of mixed-state ionic beams in collision dynamics investigations is examined. Using high resolution Auger projectile spectroscopy involving He-like ($1s^2\thinspace^1\!S, 1s2s\thinspace^{3,1}\!S$) mixed-state beams, the spectrum contributions of the $1s2s\thinspace^3\!S$ metastable beam component is effectively separated and clearly identified. This is performed with a technique that exploits two independent spectrum measurements under the same collision conditions, but with ions having quite different metastable fractions, judiciously selected by varying the ion beam charge-stripping conditions. Details of the technique are presented together with characteristic examples. In collisions of 4 MeV B$^{3+}$ with H$_2$ targets, the Auger electron spectrum of the separated $1s2s\thinspace^{3}S$ boron beam component allows for a detailed analysis of the formation of the $1s2s(^3\!S)nl \thinspace^2\!L$ states by direct $nl$ transfer. In addition, the production of hollow $2s2p\thinspace^{1,3}\!P$ doubly- and $2s2p^2\thinspace^2\!D$ triply-excited states, by direct excitation and transfer-excitation processes, respectively, can also be independently studied. In similar mixed-state beam collisions of 15 MeV C$^{4+}$ with H$_2$, He, Ne and Ar targets, the contributions of the $1s^2$, $1s2s\thinspace^{3,1}S$ beam components to the formation of the $2s2p\thinspace^{3,1}\!P$ states by double-excitation, $1s\rightarrow2p$ excitation and transfer-loss processes can be clearly identified, facilitating comparisons with theoretical calculations.

In this paper we study the class of mixed-index time fractional differential equations in which different components of the problem have different time fractional derivatives on the left hand side. We prove a theorem on the solution of the linear system of equations, which collapses to the well-known Mittag-Leffler solution in the case the indices are the same, and also generalises the solution of the so-called linear sequential class of time fractional problems. We also investigate the asymptotic stability properties of this class of problems using Laplace transforms and show how Laplace transforms can be used to write solutions as linear combinations of generalisedMittag-Leffler functions in some cases. Finally we illustrate our results with some numerical simulations.

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry. The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.

The increasingly common occurrence of antibiotic-resistant bacteria has become an urgent public health issue. There are currently some infections without any effective treatment, which require new therapeutic strategies. An attractive alternative is the design of compounds capable of disrupting bacterial communication known as quorum sensing (QS). In gram-negative bacteria, such communication is regulated by acyl-homoserine lactones (AHLs). QS allows bacteria to proliferate before expressing virulence factors. Our group previously reported that hexyloxy phenyl imidazoline (9) demonstrated 71% inhibitory activity of QS at 100 µM (IC50=90.9 µM) in Chomobacterium violaceum, a gram-negative bacterium. The aim of the present study was to take 9 as a lead compound to design and synthesize three 2-imidazolines (13-15) and three 2-oxazolines (16-18), to be evaluated as quorum sensing inhibitors on C. violaceum CV026. We were looking for compounds with a higher affinity towards the Cvi receptor of this bacterium and the ability to inhibit QS. The binding mode of the test compounds on the Cvi receptor was explored with docking studies and molecular dynamics. It was found that 8-pentyloxyphenyl-2-imidazoline 13 reduced the production of violacein (IC50=56.38 µM) without affecting bacterial growth, suggesting inhibition of quorum sensing. Indeed, compound 13 is apparently one of the best QS inhibitors known to date. Molecular docking revealed the affinity of compound 13 for the orthosteric site of the N-hexanoyl homoserine lactone (C₆-AHL) on the CviR protein. Ten aminoacid residues in the active site of C₆-AHL interacted with 13, and 7 of these are the same as those interacting with AHL. Contrarily, 8-octyloxyphenyl-2-imidazoline 14, 8-decyloxyphenyl-2-imidazoline 15 and 9-decyloxyphenyl-2-oxazoline 18 bound only to an allosteric site and thus did not compete with C₆-AHL for the orthosteric site.

Background/Aim: Rapid onset of facial ptosis can impact physical appearance and compromise the outcomes of facelift procedures. The level of vitamin D has a potential correlation with collagen formation and its deficiency with inflammatory processes that affect the breakdown of hyaluronic acid. This study aims to investigate the potential relationship between accentuated facial ptosis in women and low levels of vitamin D. Furthermore, it aims to explore preventive measures or strategies to slow down facial ptosis and enhance the longevity of facelift results. Materials and Methods: The study was focused on monitoring the vitamin D levels in women and men with advanced facial ptosis and comparing them with a control group. Results: Notably, a direct association between gender and serum vitamin D levels was observed, indicating less sustainable outcomes in women. Conclusion: Women face additional challenges in the aging process due to hormonal shifts after menopause or premenopausal, which are associated with osteoporosis and lower vitamin D levels.

(1) Background: The HIV subtype D is generally associated with a faster decline in CD4+ T cell counts, a higher viral load, and a faster progression to AIDS. However, it is still poorly characterized in Brazil. In this study, we used genomics and epidemiological data to investigate the transmission dynamics of HIV subtype D in the state of Bahia, Northeast Brazil. (2) Methods: to achieve this goal, we obtained four novel HIV-1 subtype D partial pol genome sequences using the Sanger method. To understand the emergence of this novel subtype in the state of Bahia, we used phylodynamic analysis on a dataset comprising 3,704 pol genome sequences downloaded from the Los Alamos database. (3) Results: Our analysis revealed three branching patterns, indicating multiple introductions of the HIV-1 subtype D in Brazil from the late 1980s to the late 2000s and a single introduction event in the state of Bahia. Our data further suggest that these introductions most likely originated from European, Eastern African, Western African and Southern African countries. (4) Conclusion: Understanding the distribution of HIV-1 viral strains and their temporal dynamics is crucial for monitoring the real-time evolution of circulating subtypes and recombinant forms, as well as for designing novel diagnostic and vaccination strategies. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics mediated by emerging viral strains.

This research aims to obtain empirical evidence of the influence of the masculinity of male CEOs on the of research & development, this research seeks to identify the influence of the face of mas-culinity of male CEO’s on the of research & development. The study used a quantitative approach with population and research samples using companies listed on the Indonesia Stock Exchange from 2016 to 2021. The study collected images of faces identified as male CEOs from data from the Indonesia Stock Exchange website and company as utilizing Google searches. The data analysis method in this study used Regression Ordinary Least Square (OLS) with Stata Software. Stata software is one of the regression completion procedures that has a high degree of flexibility in re-search that connects theories, concepts and data that can be done on variables in research. The findings empirically explain that the higher the face value of male CEO masculinity has an impact on reducing research & development costs, and vice versa the lower the face value of male CEO masculinity has an impact on increasing research & development. The practical implications of the research results can help the Indonesian Association of Accountants in developing Financial Accounting Standard No. 19 in Indonesia. The theoretical implications of the research results can explain the Theory of Agency and the Theory of Consistency of Behavior. The policy implications of the results of the study can provide empirical evidence that the higher the facial value of male CEO masculinity has an impact on reducing research & development, while also the lower the face value of male CEO masculinity has an impact on increasing research & development.

Abstract: The genus Acaryochloris is unique among phototrophic organisms due to the dominance of chlorophyll d in its photosynthetic reaction centres and light-harvesting proteins. This allows Acaryochloris to capture light energy for photosynthesis over an extended spectrum of up to ~760 nm in the near infra-red (NIR) spectrum. Acaryochloris sp. has been reported in a variety of ecological niches, ranging from polar to tropical shallow aquatic sites. Here, we report a new Acarychloris strain isolated from an NIR-enriched stratified microbial layer 4-6 mm under the surface of stromatolite mats located in the Hamelin Pool of Shark Bay, Western Australia. Pigment analysis, by traditional spectrometry/fluorometry, flow cytometry and spectral confocal microscopy identify unique patterns in pigment distribution that likely reflect niche adaption. For example, unlike the original A. marina species (type strain MBIC11017), this new strain, Acarychloris LARK001, shows little change in the chlorophyll d/a ratio in response to changes in light wavelength, displays a different Fv/Fm response and lacks detectable levels of phycocyanin. Indeed, 16S rRNA analysis supports the identity of the A. marina LARK001 strain as distinct from the A. marina HICR111A strain first isolated from Heron Island, previously found on the Great Barrier Reef, under coral rubble on the reef flat. Taken together, A. marina LARK001 is a new cyanobacterial strain adapted to the stromatolite matts in Shark Bay.

Background: Vitamin D was studied in regards to its possible impact on body mass reduction and metabolic changes in adults and children with obesity yet there were no studies assessing the impact of vitamin D supplementation during a weight management programme in children and adolescence. The aim of our study was to assess the influence of 26 weeks of vitamin D supplementation in overweight and obese children undergoing an integrated 12-months’ long weight loss programme on body mass reduction, body composition and bone mineral density. Methods: A double-blind randomized placebo-controlled trial. Vitamin D deficient patients ( <30 ng/ml level of vitamin D) aged 6-14, participating in multidisciplinary weight management programme were randomly allocated to receiving vitamin D (1200 IU) or placebo for the first 26 weeks of the intervention. Results: Out of the 152 qualified patients, 109 (72%) completed a full cycle of four visits scheduled in the programme. There were no difference in the level of BMI change. Although the reduction was greater in the vitamin D vs. placebo group (-4.28 ± 8.43 vs. -2.53 ±6.10) the difference was not statistically significant (p=0.319). Similarly the reduction in fat mass – assessed both using bioimpedance and DEXa was achieved, yet the differences between the groups were not statistically significant. Conclusions: Our study ads substantial results to support the thesis on no effect of vitamin D supplementation on body weight reduction in children and adolescents with vitamin D insufficiency undergoing a weight management programme. Trial registration no: NCT 02828228; trial registration date: 8 June 2016 registered in: ClinicalTrials.gov.

Several therapeutic monoclonal antibodies are approved by FDA against the PD-1/PD-L1 (programmed death-1/programmed death ligand-1) immune checkpoint, which has been a great success in cancer treatment. However, existing therapeutics, including small molecules inhibitors against PD-L1 checkpoint have certain drawbacks such as high cost and drug resistance that challenge the current available anti-PD-L1 therapy. Thereof, this study presents the screening of 32552 compounds from Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening and binding free energy refinement for the selection of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>-70 kcal/mol) for further computational investigation by comparison to co-crystallised ligand, i.e. JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and post binding free energy calculations, all the compounds exhibited intermolecular interactions (hydrogen and hydrophobic) with essential residues and substantial complex stability by comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitor in cancer immunotherapy.