Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

Protein is the proteios building block of life. Evolutionarily, its sequence is not as conserved as its structure, making it more reasonable for protein structure, instead of protein sequence, to be the descriptor of protein function. Yet, in the National Center for Biotechnology Information (NCBI) database, the number of experimentally identified protein sequences is in great excess of that of experimentally determined protein structures inside the almost-half-a-century old Protein Data Bank (PDB). For instance, GPR151 is an proton-sensing G-protein coupled receptor (GPCR) originally identified as homologous to galanin receptors. As of March 19, 2020, GPR151’s structure has not been experimentally determined and deposited in PDB yet. Thus, an ab initio modelling approach was employed here to build a three-dimensional structure of GPR151. Overall, the ab initio GPR151 model presented herein constitutes the first structural hypothesis of GPR151 to be experimentally tested in future with previously published, currently ongoing and future GPR151 studies.

The altimeter-derived ocean currents have been sparsely evaluated against in situ measurements in the Arctic, particularly for extended time periods. This study uses the extensive mooring array situated in the Fram Strait, representing one of the longest ocean current records, to investigate the relationship between in situ and satellite-derived currents in the region. The primary objective of this research is to analyze the vertical structure of the West Spitsbergen Current (WSC), its spatio-temporal coherence, and its association with surface geostrophic currents during the period of 1997-2012. To assess the vertical structure of the WSC, we utilized the Empirical Orthogonal Functions (EOF) and cross-correlation analysis between neighboring moorings. Remarkably, both velocity components exhibited robust vertical coherence, particularly within the waters of the North Atlantic Inflow, at depths exceeding 800 m. These findings underscore the potential for surface measurements to effectively complement data gaps and facilitate the reconstruction of deeper currents with a monthly temporal resolution. Notably, the surface measurements explain approximately 67% of the variance in the top 800 m of the water column.This comprehensive investigation advances our understanding of the West Spitsbergen Current and its vertical characteristics in the Arctic. Moreover, our findings highlight the valuable synergy between in situ and satellite-derived data, providing critical insights for future ocean current studies in this ecologically sensitive region.

The open-bundle structure of cytochrome c’ as an unfolding intermediate was determined by small-angle neutron scattering experiment (SANS). The four-α-helix bundle structure of Cyt c’ at neutral pH was transited to an open-bundle structure (at pD ~13), which is a joint-clubs consisting of four clubs (α-helices) connected by short loops. The compactly folded structure of Cyt c’ (radius of gyration, Rg = 18 Å for the Cyt c’ dimer) at neutral or mildly alkaline pD transitioned to a remarkably larger “open-bundle” structure at pD ~13 (Rg = 25 Å for the Cyt c’ monomer). Cyt c’ adopts an unstructured random coil structure at pD = 1.7 (Rg = 25 Å for the Cyt c’ monomer). Numerical partial scattering function analysis (joint-clubs) and ab initio modelling gave structures similar to the “open-bundle”, which retains the α-helices but loses the bundle structure.

Background and Objectives: To assess femoral shaft bowing (FSB) in the coronal and sagittal planes and introduce the clinical implications of total knee arthroplasty (TKA) by analyzing a three-dimensional (3D) model with virtual implantation of the femoral component. Materials and Methods: Sixty-eight patients (average age: 69.1 years) underwent 3D model reconstruction, incorporating medullary canals, by importing computed tomography (CT) data into Mimics® software. A mechanical axis (MA) line was drawn from the midportion of the femoral head to the center of the intercondylar notch; proximal/distal straight centerlines (length, 60 mm; diameter, 1 mm) were placed in the center of the medulla canal. Acute angles between the two centerlines were measured as lateral and anterior bowing. The acute angle by distal centerline and MA line was measured as distal coronal and sagittal alignment in both anteroposterior (AP) and lateral views. The diameter of curve (DOC) of the medulla along the posterior border was measured. Results: The mean lateral bowing on the AP view was 3.71°, and the mean anterior bowing on the lateral view was 11.82°. The average DOC of the medullary canal was 1501.68 mm. The distal coronal alignment of all femurs was an average of 6.40°, and the distal sagittal alignment was 2.66°. Overall, 22 femurs had coronal bowing, 42 had sagittal bowing, and 15 had both. Conclusion: In Asians, FSB is present in coronal, sagittal, or both directions. Increased anterolateral FSB may lead to cortical abutment in the sagittal plane despite limited space in the coronal plane. During TKA, distal coronal alignment can guide distal femoral valgus cut angle, whereas distal sagittal alignment helps anticipate femoral component positioning, avoiding anterior notching. Osteotomy along the anterior cortical bone to prevent notching may result in outliers due to differences between distal sagittal alignment and distal anterior cortical axis.

The three-dimensional structure of Gulf of Mexico’s warm-core rings, detaching from the Loop Current, is investigated using satellite altimetry and a large set of ARGO float profiles. Reconstruction of the Loop Current rings (LCRs) vertical structure from sea surface height observations is made possible by the use of the gravest empirical modes method (GEM). The GEMs are transfer functions that associate a value of temperature and salinity for each variable pair {dynamic height;pressure}, and are computed by estimating an empirical relationship between dynamic height and the vertical thermohaline structure of the ocean. Between 1993 and 2021, 40 LCRs were detected in the altimetry and their three-dimensional thermohaline structure was reconstructed, as well as a number of dynamically relevant variables (geostrophic and cyclogeostrophic velocity, relative vorticity, potential vorticity, available potential energy and kinetic energy density etc.). The structure of a typical LCR was computed by fitting an analytical stream function to the LCRs dynamic height signature and reconstructing its vertical structure with the GEM. The total heat and salt contents and energy of each LCR were computed and their cumulative effect on the Gulf of Mexico’s heat, salt and energy balance is discussed. We show that LCRs have a dramatic impact on these balances and estimate that residual surface heat fluxes of -13 Wm−2 are necessary to compensate their heat input, while the fresh water outflow of the Mississippi river approximately compensates for their salt excess input. An average energy dissipation of O[10−10−10−9] Wkg−1 would be necessary to balance their energy input.

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.

Ontological premises have profound theoretical implications. This analysis posits a single, universal structure composed of two ontic entities: discrete, quantized units of space ("Planck Spheres") and a State of Absolute Nothingness (the "SOAN"). Planck Spheres and the SOAN form a physical, ultra-high (3 x N) dimensional space ("Planck Space") and a discrete 3D space (or "4D spacetime"). Together, Planck Space and 4D spacetime form a tightly integrated ((3 x N) + 3) hyperspace (the "Dual Ontology"). Critically, a one-to-one mapping and identity exists between the Planck Spheres comprising 4D spacetime and Planck Space. The Dual Ontology conjecture supports radically simplified physical explanations for three distinct areas of theoretical physics: First, the conjecture reconciles fundamental issues in Special Relativity and quantum mechanics by explaining why single and N-body quantum states (a) dynamically evolve in 4D spacetime subject to the speed of light and (b) instantaneously collapse in a physical Planck Space that is not subject to Special Relativity. Second, the temporal and physical asymmetry between the dynamic evolution of quantum states in 4D spacetime subject to Special Relativity and the instantaneous collapse of quantum states in a Planck Space where Special Relativity is inapplicable explains quantum path irreversibility and the arrow of time. Third, at or near the heat death of 4D spacetime, the instantaneous collapse of the energy content of Planck Space and the simultaneous transition of 4D spacetime's extremely widely dispersed energy content to a non-singular, generally localized volume at t = 0 explains 4D spacetime's isotropy, homogeneity, extremely high energy, pressure, and temperature, flatness, and low gravitational entropy. It also explains the horizon and fine-tuning problems.

This letter attempts to find splashing height of liquid-filled container drop impact to a solid surface by dimensional analysis (DA). Two solutions were obtained by both traditional DA and directed DA without solving any governing equations. It is found that the directed DA can provide much more useful information than the traditional one. This study shows that the central controlling parameter is called splash number $\mathrm{Sp}=\mathrm{Ga} \mathrm{La}^\beta=(\frac{gR^3}{\nu^2})(\frac{\sigma R}{\rho \nu^2})^\beta$, which is the collective performance of each quantity. The splash height is given by $ \frac{h}{H}=(\frac{\rho\nu^2}{\sigma R})^\alpha f[\frac{gR^3}{\nu^2}(\frac{R\sigma}{\rho\nu^2})^\beta]=\frac{1}{\mathrm{La}^\alpha}f(\mathrm{Ga}\cdot \mathrm{La}^\beta)$. From the physics of the splashing number, we can have a fair good picture on the physics of the liquid splashing as follows: the jets propagation will generate vortex streets from the container bottom due to sudden pressure increasing from drop impact (water-hammer effect), which will travel along the container sidewall to the centre of the container and subsequently excite a gravity wave on the liquid surface. The interaction between the gravitational force, surface force and viscous force is responsible for creating droplet splash at the liquid surface.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

Hemoconcentration membranes used in cardiopulmonary bypass require a pore structure design with high pure water permeability, and which does not allow protein adsorption and useful protein loss. However, studies on hemoconcentration membranes have not been conducted yet. The purpose of this study was to analyze three-dimensional pore structures and protein fouling before and after blood contact with capillary membranes using the tortuous pore diffusion model and a scanning probe microscope system. We examined two commercially available capillary membranes of similar polymer composition that are successfully used in hemoconcentration clinically. Assuming the conditions of actual use in cardiopulmonary bypass, we perfused these membranes with bovine blood. Pure water permeability before and after bovine blood perfusion was measured using the dead-end filtration. The scanning probe microscopy system was used for analysis. High-resolution three-dimensional pore structures on the inner surface of the membranes were observed before blood contact. On the other hand, pore structures after blood contact could not be observed due to protein fouling. The pore diameters calculated by the tortuous pore diffusion model and scanning probe microscopy were mostly similar and could be validated reciprocally. Achievable pure water permeabilities showed no difference despite protein fouling, leading to low values of albumin SC. This is due to the mechanism that protein fouling occurs on the membrane surface, while there is little internal pore blocking. Therefore, controlling the fouling is essential for membranes in medical use. These characteristics of the hemoconcentration membranes examined in this study are suitable for clinical use.

This research work aims to develop a mathematical modeling for production-inventory systems. Two mathematical models are present: An infinite dimensional, partial differential equation (PDE), production level modeling is present and a finite dimensional system for a coupled dynamic pricing, production rate and inventory level ordinary differential equations (ODE), integrating a proper Lyapunov stability analysis of the dynamical system and simulations.

The Cosmic Theory of Structure (CTS) model presents a comprehensive framework that integrates gravitational waves, neutrinos, dark matter, and quantum field interactions. This model aims to provide a unified understanding of the universe's formation and evolution. The CTS model has undergone rigorous validation using the latest datasets, demonstrating its robustness and predictive power. Key updates include detailed mathematical formulations, refined theoretical frameworks, and enhanced descriptions of fundamental cosmic phenomena. This manuscript presents the final validated version of the CTS model, highlighting its alignment with observational data and its implications for future research in cosmology and quantum physics.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

This research focuses on exploring generalized electron emissions in one-dimensional conducting materials, specifically examining field emission and thermionic emission. Additionally, the study investigates one-dimensional thermal radiation. The current density is derived for both one-dimensional thermionic emission and one-dimensional field emission. A generalized current density in one dimension is devised, taking into account arbitrary accelerating fields and temperature conditions. The formula for the one-dimensional current density is depicted with accelerating field and temperature across various work function materials. The current is also represented as a function of both temperature and electric field for various temperatures.

This paper reviews the unilateral and bilateral, one- and two-dimensional Laplace transforms. The unilateral and bilateral Laplace transforms are compared in the one-dimensional case, leading to the formulation of the initial-condition theorem. This problem is solved with all generality in the one- and two-dimensional cases with the bilateral Laplace transform. General two-dimensional linear systems are introduced and the corresponding transfer function defined.

The paper primarily demonstrates that the three internal triangles formed by connecting any point on a midsegment with the vertices of a generic triangle satisfy the geometric Proof of the Pythagorean theorem in Euclidean geometry. Moreover, this study elucidates the Pythagorean relationships inherent within three-dimensional geometric constructs resulting from the arrangement of three-dimensional spatial triangles. This geometric relationship, akin to a generalized extension of the Pythagorean theorem, unveils a unique spatial region characterized by this harmonious area interrelation among triangles.

Nobel metal nanohole arrays have been used extensively in chemical and biological systems due to their fascinating optical properties. Gold nanohole arrays (Au NHAs) were prepared as surface plasmon polaritons (SPP) generators for the surface-enhanced sum-frequency generation (SFG) detection of 4-Mercaptobenzonitrile (4-MBN). The angle-resolved reflectance spectra revealed that the Au NHAs have three angle-dependent SPP modes and two non-dispersive localized surface plasmon resonance (LSPR) modes under different structural orientation angles (sample surface orientation). An enhancement factor of ~30 was achieved when the SPP and LSPR modes of the Au NHAs were tuned to match the incident visible (VIS) and output SFG, respectively. This multi-mode matching strategy provided flexible controls and selective spectral windows for surface-enhanced measurements, and was especially useful in nonlinear spectroscopy where more than one light beam involved. The structural orientation- and power-dependent performance demonstrated the potential of plasmonic NHAs in SFG and other nonlinear sensing applications, and provided a promising surface molecular analysis development platform.

This paper presents a method for producing a gravity field through an electromagnetic field. The electromagnetic field can produce a positive or negative gravity field. The relationship between gravity force and electromagnetic is unknown. Former studies by theoretical physics predict the relationship between these two forces. Based on the general balance theory in six dimensions of space and time, the electromagnetic field was studied from this viewpoint. Three-dimensional waves oscillate in the fourth dimension and electromagnetic waves distort space-time. Aggregating these distortions can behave like a positive or negative gravity field. Consequently, the production of energy is possible from gravitational fields.

Two-dimensional (2D) ice I is an atomic-level ice that is composed of two interlocked atom-ic layers saturated with hydrogen bonds. It has recently been experimentally observed but its properties have yet to be clarified. Accordingly, we theoretically studied the hydrophobic properties of 2D ice I. On the contrary, simulation of a hydrogen fluoride molecule on a 2D ice surface manifested that it destroyed the 2d ice structure and connected new hydrogen bonds with water molecules. Investigations of the interfacial effect between 2D and three-dimensional (3D) ice films indicated that the network structure of 2D ice was not de-stroyed by a 3D ice surface, as the former was saturated with hydrogen bonds. However, the surface of 3D ice reorganized to form as many hydrogen bonds as possible. Thus, the 2D ice film was hydrophobic and inhibited the growth of 3D ice. This shows that if 2D ice can be produced on an industrial scale, it could be used as an anti-3D-icing agent under low tem-perature.

The paper considers new effects of the nanoscale state of matter, which open up prospects for the creation of electronic devices using new physical principles. The contact of chemically homogeneous different sizes hydrated nanoparticles of yttrium-stabilized zirconium oxide (ZrO2 – x %mol Y2O3, x=0, 3, 4, 8; YSZ) with particle sizes of 7.5 nm and 7,5 nm; 7.5 nm and 9 nm; 7.5 nm and 11 nm; 7.5 nm and 14 nm in the form of compacts obtained using high hydrostatic pressure (HP-compacts of 300MPa) was studied at direct and alternating current. A unique size effect of the nonlinear (semiconductor) dependence of the electrical properties (in the region U <2.5 V, I ≤ 2.7 mA) of the contact of different-sized YSZ nanoparticles of the same chemical composition is revealed, which indicates the possibility of creating semiconductor structures of a new type based on chemically homogeneous nanostructured systems. The electronic structure of the near-surface regions of nanoparticles of a special type of oxide materials and the possibility, on this basis, to obtain specifically rectifying properties of the contacts were studied theoretically. Models of surface states of the Tamm type are constructed, but considering the Coulomb long-range action. The discovered variance and its dependence on the curvature of the surface of nanoparticles made it possible to study the conditions for the formation of a contact potential difference in cases of nanoparticles of the same radius (synergistic effect), different radii (doped and undoped variants), as well as to discover the possibility of describing a group of powder particles from material within the Anderson model. The established effect makes it possible to solve the problem of diffusion instability of semiconductor heterojunctions and opens up prospects for creating electronics devices with a fundamentally new level of properties for use in various fields of the national economy and breakthrough critical technologies.

Two modal decomposition techniques, including proper orthogonal decomposition (POD) and dynamic mode decomposition (DMD), are used to identify the wake patterns past single and two crossing cylinders in 60° and 90° arrangements with gap ratio G = 4. The flow is simulated using direct numerical simulations (DNS) for Reynolds numbers Re = 100. The spatial scale of flow decreases with increasing modal frequency from the modal analysis. Two main modes are identified in the wake of the cylinders, namely spatially antisymmetric and symmetric modes. Antisymmetric and symmetric modes are related to cylinders’ vortex shedding and shedding vortices’ shift motion, respectively, whose frequencies are odd and even multiples of cylinders’ lift force frequency. In addition, a low-frequency mode concerning the shadowing effect of the downstream cylinder (DC) in 90° arrangement is found in the wake of the DC centre.

The aim of this study was to examine n-balls, n-simplices and n-orthoplices in real dimensions using novel recurrence relations that removed indefiniteness present in known formulas. They show that in negative, integer dimensions volumes of n-balls are zero if n is even, positive if n = -4k - 1, and negative if n = -4k - 3, for natural k. Volumes and surfaces of n-cubes inscribed in n-balls in negative dimensions are complex, wherein for negative, integer dimensions they are associated with integral powers of the imaginary unit. The relations are continuous for n Î ℝ and show that the constant of π is absent for 0 ≤ n < 2. For n < -1 self-dual n-simplices are undefined in negative, integer dimensions and their volumes and surfaces are imaginary in negative, fractional ones, and divergent with decreasing n. In negative, integer dimensions n-orthoplices reduce to the empty set, and their real volumes and imaginary surfaces are divergent in negative, fractional ones with decreasing n. Out of three regular, convex polytopes present in all natural dimensions, only n-orthoplices, n-cubes (and n-balls) are defined in negative, integer dimensions.

Developing particles of different anisotropic shapes are the hot topic since decades as they guarantee some special features of properties not possible through other means. Again, controlling atoms to develop certain size and shape particle is a quite challenging job. In this study, gold particles of different shapes are developed via pulse-based electronphoton-solution interface process. Gold atoms of certain transition state develop monolayer assembly at solution surface around the light glow (known in argon plasma) being generated at bottom of copper capillary (known in cathode). The rate of uplifting gold atoms to solution surface is being controlled by forcing energy (travelling photons) pursuing electrons and high energy photons (in high density) entering to solution. Gold atoms dissociated from the precursor under dissipating heat energy into the solution supplied under propagating photons characteristic current through immersed graphite rod (known in anode). Placing packets of nano shape energy of tuned pulse protocol over compact monolayer assembly comprising transition state atoms develop tiny-sized particles of formed shape. On separation of joint tiny particles into two equilateral triangular-shaped tiny particles, exerting forces of surface format elongate atoms of one-dimensional arrays converting them into structures of smooth elements. Due to immersing level of force, such tiny-shaped particles pack from different zones at centre of light glow where they assembled structures of smooth elements for developing mono-layers of different shapes of particles. Developing one-dimensional particles deal assembling of structures of smooth elements of packing tiny-shaped particles from nearly rearward zones of reflection of north-south poles, whereas, developing multi-dimensional particles deal assembling of structures of smooth elements of packing tiny-shaped particles from the east-west poles and near regions. Depending on the number of assembled structures of smooth elements at point of nucleation, packing of tiny-shaped particles from different zones develop different shapes of the anisotropic particles. At fixed precursor concentration, increasing the process time results into develop particles of low aspect ratio. Under tuned parameters, developing mechanisms of particles exhibiting unprecedented features are discussed.

GPT-4 was released in March 2023 to wide acclaim, marking a very substantial improvement across the board over GPT-3.5 (OpenAI's previously best model, which had powered the initial release of ChatGPT). Despite the genuinely impressive improvement, however, there are good reasons to be highly skeptical of GPT-4's ability to reason. This position paper discusses the nature of reasoning; criticizes the current formulation of reasoning problems in the NLP community and the way in which the reasoning performance of LLMs is currently evaluated; introduces a collection of 21 diverse reasoning problems; and performs a detailed qualitative analysis of GPT-4's performance on these problems. Based on the results of this analysis, the paper argues that, despite the occasional flashes of analytical brilliance, GPT-4 at present is utterly incapable of reasoning.

Tuberculosis (TB) is a contagious disease, caused by Mycobacterium tuberculosis (MTB) that has infected and killed a lot of people in the past. At present treatments against TB are available at a very low cost. Since these chemical drugs have many adverse effects on health, more attention is now given on the plant-derived phytochemicals as potential agents to fight against TB. In this study, 5 phytochemicals, 4-hydroxybenzaldehyde, benzoic acid, bergapten, psoralen, and p-hydroxybenzoic acid, are selected to test their potentiality, safety, and efficacy against two potential targets, the MTB RNA polymerase and enoyl-acyl carrier protein (ACP) reductase, the InhA protein, using various tools of in silico biology. The molecular docking experiment, drug-likeness property test, ADME/T-test, P450 SOM prediction, pharmacophore mapping, and modeling, solubility testing, DFT calculations, and PASS prediction study had confirmed that all the molecules had the good potentiality to inhibit the two targets. However, two agents, 4-hydroxybenzaldehyde and bergapten were considered as the best agents among the five selected agents and they also showed far better results than the two currently used drugs, that function in these pathways, rifampicin (MTB RNA polymerase) and isoniazid (InhA protein). These two agents can be used effectively to treat tuberculosis.

We synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids using an easy and short step synthetic route. All compounds were tested in vitro against a set of four protein targets identified as key elements in diabetes: GPR40, aldose reductase (AKR1B1), PPARγ and GLUT-4. Compound 1 displayed an EC₅₀ value of 0.075 μM against GPR40 and was an AKR1B1 inhibitor, showing IC₅₀ = 7.4 μM. Compounds 2 and 3 behave as AKR1B1 inhibitors, GPR40 agonists and showed an increase of 2 to 4-times in the mRNA expression of PPARγ, as well as the GLUT-4 levels. Docking studies were conducted in order to explain the polypharmacological mode of action and the interaction binding mode of the most active compounds on these targets. Compounds 1-3 were tested in vivo at 100 mg/kg dose, being 2 and 3 orally actives, reducing glucose levels in a non insulin-dependent diabetes mellitus mice model. Compounds 2 and 3 showed robust in vitro and in vivo efficacy, and could be considered as promising multitarget antidiabetic drug candidates. This is the first report of a single molecule with these four polypharmacological target action.

The accurate assessment of wound size is a critical step in advanced wound care management. This study aims to introduce and validate a Light Detection and Ranging (LiDAR) technique for measuring wound size. Twenty-eight wounds treated from December 2022 to April 2023 at the Chunganam National University Hospital were analyzed. All wounds were measured using three techniques; conventional ruler methods, the LiDAR technique, and ImageJ analysis. Correlation analysis, linear regression, and Bland-Altman plot analysis were conducted to validate the accuracy of the newly introduced method. The measurement results (Mean ± Standard deviation) obtained using the Ruler method, LiDAR technique, and ImageJ analysis were 112.99 ± 110.07 cm², 73.59 ± 72.97 cm², and 74.29 ± 72.15 cm², respectively. The Pearson correlation coefficient was higher in the LiDAR application (0.995) than the conventional ruler methods (Mean difference; -5.0000 cm2), as was the degree of agreement (Mean difference; 38.6933 cm2). Wound size measurement using LiDAR is a simple and reliable method that allows practitioners to conveniently assess wounds with a flattened and irregular shape. However, non-flattened wounds cannot be assessed owing to the technical limitations of LiDAR.

In this short communication, we conducted first-principles calculations to explore the stability of boron monochalcogenides (BX, X=S, Se or Te), as a new class of two-dimensional (2D) materials. We predicted BX monolayers with two different atomic stacking sequences of ABBA and ABBC, referred in this work to 2H and 1T, respectively. Analysis of phonon dispersions confirm the dynamical stability of BX nanosheets with the both 2H and 1T atomic lattices. Ab-initio molecular dynamics simulations reveal the outstanding thermal stability of all predicted monolayers at high temperatures over 1500 K. BX structures were found to exhibit high elastic modulus and tensile strengths. It was found that BS and BTe nanosheets can show high stretchability, comparable to that of the graphene. It was found that all predicted monolayers exhibit semiconducting electronic character, in which 2H structures present lower band-gaps as compared with 1T lattices. The band-gap values were found to decrease from BS to BTe. According to the HSE06 results, 1T-BS and 2H-BTe show respectively, the maximum (4.0 eV) and minimum (2.06 eV) electronic band-gaps. This investigation introduces boron monochalcogenides as a novel class of 2D semiconductors with remarkable thermal, dynamical and mechanical stability.

Three-dimensional graphene (3DG) sponge has attracted increasing attention because it combines the unique properties of cellular materials and the excellent performance of graphene. The preparation of 3DG sponge depends mainly on the self-assembly of graphene oxide sheets. Here, we demonstrate facile fabrication of 3DG sponge with a large-scale and ordered porous structure, exploiting the liquid crystals of large graphene oxide (LGO) and ultralarge graphene oxide (ULGO) sheets. The resulting materials exhibit a low density, high porosity and elasticity. Our work explores a new strategy for organizing the ordered alignment of controlled large GO sheets and exploring the relationship between the microstructures and mechanical properties of 3DG sponge.

This study investigates the therapeutic potential of new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner's chronic unpredictable mild stress model of depression in 48 male Wistar rats was used a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group receiving saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light-dark box, were used to assess the animals' conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to intact animals. These results suggest that Compound I has a reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.

The authors previously found a model of universal quantum computation by making use of the coset structure of subgroups of a free group $G$ with relations. A valid subgroup $H$ of index $d$ in $G$ leads to a \lq magic' state $\left|\psi\right\rangle$ in $d$-dimensional Hilbert space that encodes a minimal informationally complete quantum measurement (or MIC), possibly carrying a finite \lq contextual' geometry. In the present work, we choose $G$ as the fundamental group $\pi_1(V)$ of an exotic $4$-manifold $V$, more precisely a \lq small exotic' (space-time) $R^4$ (that is homeomorphic and isometric, but not diffeomorphic to the Euclidean $\mathbb{R}^4$). Our selected example, due to to S. Akbulut and R.~E. Gompf, has two remarkable properties: (a) it shows the occurence of standard contextual geometries such as the Fano plane (at index $7$), Mermin's pentagram (at index $10$), the two-qubit commutation picture $GQ(2,2)$ (at index $15$) as well as the combinatorial Grassmannian Gr$(2,8)$ (at index $28$) , (b) it allows the interpretation of MICs measurements as arising from such exotic (space-time) $R^4$'s. Our new picture relating a topological quantum computing and exotic space-time is also intended to become an approach of \lq quantum gravity'.

The activity and cyclability of Cu-MOF-74 as catalyst was studied for the ligand-free C-O cross-coupling reaction of 4-nitrobenzaldehyde (NB) with phenol (Ph) to form 4-formyldiphenyl ether (FDE). Cu-MOF-74 is characterized by unsaturated copper sites in a highly porous metal-organic framework. The influence of solvent, reaction temperature, NB/Ph ratio, catalyst concentration and basic agent (type and concentration) were evaluated. High conversions were achieved at 120°C, 5 mol% of catalyst, NB/Ph ratio of 1:2, DMF as solvent and 1 equivalent of K2CO3 base. The activity of Cu-MOF-74 material was higher than other ligand-free copper catalytic systems tested in this study. This catalyst was easily separated and reused in five successive runs, achieving a remarkable performance without significant porous framework degradation. The leaching of copper species in the reaction medium was negligible. The O-arylation between NB and Ph took place only in the presence of Cu-MOF-74 material, being negligible without the solid catalyst.

The paper proposes a universal algorithm for parallelizing calculations that arise when using highly-optimized minimization functions available in many computing packages. The main idea of the proposed algorithm is based on the fact that although the “inner workings” of the minimization function used may not be known to the user, it inevitably uses in its work auxiliary functions that implement the calculation of the minimized functional and its gradient, which are usually implemented by the user, which means that in most cases they can be parallelized relatively easily. The paper discusses in detail both the parallelization algorithm and its software implementation using MPI parallel programming technology. Examples of the software implementation of the proposed algorithm are demonstrated using the Python programming language, but can be easily rewritten using the C/C++/Fortran programming languages.

This paper describes the formulations for viscoplasticity of metals based on the Chaboche and Delobelle model. The implementations of the viscoplastic models were detailed herein and then implemented via user subroutines for material models (UMAT) in ABAQUS. Two typical metals, i.e., 316 Stainless Steel and Zircaloy-4, were chosen as examples and their viscoplastic behaviors were captured. Numerical simulations are compared to reported experiments to validate the models and the UMAT codes. Typical viscoplastic behaviors of both metals, such as stress relaxation and creep, were captured well against available experiments. We publicize all the data and codes via: https://github.com/XJTU-Zhou-group/ABAQUS_UMAT_316ss_Zr4.

We demonstrate, for the first time, a highly sensitive detection of 4-methylimidazole (4-MeI), a carcinogenic material, by applying an electric field enhancement technique using a terahertz (THz) metamaterial at the THz region. The THz metamaterials were fabricated with a metal array using an electric-field-coupled inductor-capacitor (ELC) resonator structure, and FDTD simulation showed good agreement with experimental results. We measured the THz spectra of the metamaterials to detect 4-MeI concentrations of 0, 1, 2, 5, 10, 15, and 20 mg/L. The resonance frequency of the metamaterial was shifted by approximately 8 GHz and transmittance at the resonance frequency increased to 2 x 10-3 as the concentration was increased, up to 20 mg/L. Our study provides new insight into application of metamaterials to detect carcinogen using a THz technique.

Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone 19 and 20 displayed the highest antileishmanial activities, with EC₅₀ values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS).

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

IL1RA intron 2 86-bp repeat and IL4 intron 3 70-bp repeat are VNTRs that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher adiposity - even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. TBF was also significantly higher in those with IL1RA II allele compared with I allele (31.79 ± 2.52 vs. 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 3 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

On the basis of the golden ratio and the compasseses, every angle was divided into three equal parts. In general, it has been proven that the problem of triangulation of an angle cannot be solved on the basis of the golden ratio and the expanding of the angle. The relationship of golden relativity with Pi number and Euler's number has not been investigated to solve impossible problems. According to the investigation of events in six-dimensional space-time, with the simultaneous movement of two arms of the compasses based on the golden ratio, every angle was divided into three equal parts. The growth rate based on the golden ratio is the key to solving the most intractable mathematical and physical problems.

Background: Scaffold (SCA) functionalization with aptamers (APT) provides adsorption of specific bioactive molecules on biomaterials surface. The aim of this study was to observe if SCA enriched with anti-fibronectin APT can favor coagulum (PhC) and osteoblasts (OSB) differentiation. Methods: 20 ug of APT was functionalized on SCA by simple adsorption. For PhC formation, SCAs were inserted into rat calvaria defects for 17 hours. Following proper transportation (Buffer solution-PB), OSB (UMR-106 lineage) were seeded over PhC + SCAs with and without APT. Cells and PhC morphology, PhC cell population, protein labelling and gene expression were observed in different time points. Results: The APT induced higher ALP and BSP immunolabeling in OSB. CD90, CD45 and CD44 expression was more detected in APT group than when scaffolds were not functionalized. Additionally, an enriched and dense fibrin network and different cell types were observed, with more OSB and white blood cells in PhC formed on SCA with APT. The gene expression showed higher TGF-β1 detection in SCA with APT. Conclusions: The SCA functionalization with fibronectin aptamers provides a selective expression of proteins related to coagulation pattern and osteo differentiation. Additionally, aptamers increase TGF-β1 gene expression, which is highly associated with improvements in regenerative therapies.

Highly efficient, broadband and distinctively structured electromagnetic wave (EMW) absorption materials exhibit huge exceptions with multi-functions in both military and civilian fields. Searching the relationship between structural and EMW performance is beneficial to develop outstanding microwave absorption materials, and has become an attractive research topic. In this study, we briefly reviewed the different EMW absorption mechanisms and key influence factors, then, present the latest developments in low-dimensional (LD) EMW absorption materials. We provide a comprehensive discussion of remarkable examples and summarize the main information related to the structure-function relationship of dimensional design and structural engineering in order to facilitate the rapid evolution of this fascinating field.

In research applications across several areas, noise removal is indispensable for accuracy of final results. Noise is caused due to physical principals, such as background electronic noise, quantum effect, and wave rebound effect to name a few. Noise removal can help improve results in medical, astronomy, defense, and numerous other fields. Addressing this limitation would result in potentially low cost, automatic, and reliable systems. In this paper, a generalized new approach i.e. Multi-Frame Noise Removal (MFNR) is proposed for noise removal. Given any type of data, the probability density function (PDF) of the noise can be determined. Herein, we extracted the noise PDF parameters using KDE (Kernel Density Estimation). Because the data is corrupted by “deterministic” noise, hence can be cleaned. This could be used as a general purpose noise removal tool. The data point with same position in multiple frames helps us determine the noise PDF characteristics and hence making it possible to remove noise. The conventional wisdom which states that noise removal and detail preservation are contrary to each other is not true for MFNR. Experimental results validate our proposed method which showed practically complete noise reduction based on number of frames used, as compared to existing benchmark methods.

The recently proposed Holography-inspired approach to quantum gravity is reviewed and expanded. The approach is based on the foliation of the background spacetime and reduction of the offshell states to the physical states. Careful attention is paid to the boundary conditions. It is noted that the outstanding problems such as the cosmological constant problem and black hole information can be tackled from the common thread of the quantized gravity. One-loop renormalization of the coupling constants and the beta function analysis are illustrated. Active galactic nuclei and gravitational waves are discussed as the potential applications of the present quantization scheme to astrophysics.

Current neural network models can demonstrate reasonable-looking behavior, considered by some developers and researchers human-like. For example, a large language model GPT-3 is susceptible to human-like cognitive biases. Yet there is no data of such models solving emotional intelligence (EI) tasks. They are connected to the abilities that has been previously considered as specifically human EI is an important aspect of human communication. The ability to understand and respond to emotional cues is essential for effective communication. Therefore, it is crucial to determine the ways AI models such as ChatGPT demonstrate EI. The present research aims to measure the EI of GPT-4, a large language model trained by OpenAI. Russian version of the Mayer–Salovey–Caruzo Emotional Intelligence Test sections B, C, D, F, G and H were used in this research. High points were obtained in Understanding emotions scale and Strategic EI. Mean points are obtained in Managing emotions scale. Low and less reliable values are obtained in Using emotions to facilitate thought scale. Thus, GPT-4 seems already capable of identifying emotions in text and describing techniques for managing them. However, complex cases and irregular situations requiring emotions qualitative analysis would be a hard task for GPT-4.

Background: In 2023, ChatGPT-4 has been impactful across several sectors including healthcare, where it aids in medical information analysis and education. Electronic Patient-Reported Outcomes (ePROs) play a crucial role in monitoring cancer patients’ post-treatment symptoms, enabling early in-terventions. However, managing the voluminous ePRO data presents significant challenges. This study assesses the feasibility of utilizing ChatGPT-4 for analyzing side effect data from ePROs. Methods: Thirty cancer patients were consecutively collected via a web-based ePRO platform, reporting side effects over 4 weeks. ChatGPT-4, simulating oncologists, dietitians, and nurses, analyzed this data and offered improvement suggestions, which were then reviewed by professionals in those fields. Results: Two oncologists, two dieticians and two nurses evaluated the AI’s performance across roles with 540 reviews. ChatGPT-4 excelled in data accuracy and completeness, and was noted for its empathy and support, enhancing communication and reducing caregiver stress. It was particularly effective as a dietician. Discussion: ChatGPT-4 shows promise in processing ePRO data with high accuracy, suggesting that AI can enhance clinical decision-making. Nevertheless, its limitations in emotional engagement highlight the need for AI to supplement, not replace, human care. Emphasizing the role of dietitians underscores the importance of nutritional advice in cancer care. Future studies will further explore the feasible application of AI and ePRO in cancer care clinical processes.

Cinnamate 4-hydroxylase (C4H) is a cytochrome P450-dependent monooxygenase enzyme that catalyzes a key step in phenylpropanoid metabolism in plants. However, there is very limited information on the function of C4H in medicinal plants. In the present study, the C4H gene from the Ferula pseudalliacea genome (named FpC4H) was cloned and characterized. In addition, the expression levels of FpC4H in the roots, stems, leaves, flowers and seeds were investigated via real-time PCR. FpC4H showed the most similarity with C4H proteins from Daucus carota. The results predicted that FpC4H, as well as its orthologs, is an unstable and hydrophilic protein. A high genetic distance was observed between FpC4H and C4H from monocots based on evolutionary analysis. Moreover, a variable region related to the variable function of C4H was detected in conserved domain region of C4H proteins. Protein structure analysis revealed that isoleucine and leucine residues are frequently present in the binding region of FpC4H, and two ion binding regions, cysteine258 and asparagine217, were identified in the 3D structure of FpC4H. Expression analysis revealed that the FpC4H gene is expressed in all organs of F. pseudallicea. A low expression level of FpC4H was recorded in leaves, and a high expression level was observed in flower tissues. Based on the expression profile, FpC4H seems to be linked to a high content of phenolic compounds in flowers.

Chat generative pre-trained transformer (ChatGPT) is a developed language model and a subgroup of artificial intelligence (AI) which has demonstrated noticeable innovation in interactions between computer models and human studies. The release of ChatGPT in November 2022 attracted over 100 million users in a short time. It has unlimited applications in different fields of studies such as technology and science. ChatGPT utilizes deep learning and internet text to produce responses that resemble human language, although their accuracy is not always guaranteed. ChatGPT and GPT-4 can make a huge revolution in biology, medical, dental research, and health care. However, it's important to acknowledge the limitations of ChatGPT such as limitation in accessing the latest data. ChatGPT has generated both excitement and concern regarding its potential misuse. Its utilization in scientific publications has sparked debates and prompted the development of policies to govern the use of it. Although ChatGPT has certain limitations, it could impact on many different fields of study. There are challenges associated with using ChatGPT in the field of laboratory medicine and biology, particularly in the interpretation of test results. In this article, we review some of the applications of ChatGPT and GPT-4 in biology, dental and medical studies, and concerns about ChatGPT. Despite ChatGPT's conversational abilities are impressive, there are important considerations regarding its use in different fields of research and academic public.

In this research, first a binary nanocomposite of magnetic recyclable photocatalyst Fe₃O₄/TiO₂, was synthesized by sol gel technique. Then, in order to enhance the photocatalytic activity of the synthesized nanocomposite, it was deposited by silver nanoparticles for using in degradation of organic pollutants 2, 4-dichlorophenol (2, 4-DCP) under visible light. A range of analytical techniques including XRD, FESEM/EDX, DRS, VSM and N₂ physisorption were employed to reveal the crystal structure, morphology and property of the nanocomposites. We obtained 32% and 55% degradation of 2, 4-DCP under visible light after 180 min irradiation in the presence of Fe₃O₄/TiO₂ and Fe₃O₄/TiO₂/Ag respectively. Thus, the excellent visible light photocatalytic activity of Fe₃O₄/TiO₂/Ag sample can be attributed to the surface plasmon resonance effect of Ag nanoparticles deposited on Fe₃O₄/TiO₂ nanocomposite.

A study has been carried out on Ta and Nb recovery by liquid-liquid extraction process using 4-methylacetophenone (4-MAcPh) as organic phase. The 4-MAcPh was compared to methylisobutylketone (MIBK) with respect to extraction efficiencies (kD values) at different concentrations of H2SO4 in the aqueous phase. The results showed a similar extraction of Nb for both solvents. However, for Ta extraction efficiency is increased by a factor of 1.3 for 4-MAcPh. In addition, the MIBK solubilized completely after 6 mol L-1 of H2SO4 against only a loss of 0.14 to 4% for 4-MAcPh between 6 and 9 mol L-1 of H2SO4. The potential of 4-MAcPh has also been studied to selectively recover Ta from a model capacitor waste solution. The results showed a selectivity for Ta in the presence of impurities such as Fe, Ni, Mn. The 4-MAcPh also presents the advantage of having physicochemical properties adapted to its use in liquid-liquid extraction technologies such as mixer-settlers.

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

Gastric mixing relies both on enzymatic reactions and mechanical solicitations through antral contraction waves (ACWs). This work aims at discussing the influence of ACWs frequency and digesta viscosity on human gastric mixing efficiency by comparison with that of a soft elastic reactor (SER), that induces mixing by vibration of its wall in a similar way as ACWs promote stomach motility. The SER mixing curve was considered in order to determine the flow regime reached during gastric mixing. The number of contractions required to achieve homogenization was found to depend on the viscosity of the stomach content and the ACWs amplitude. Moreover, it was deduced from the same range of SER and ACWs operating points that the mechanical solicitation provided by human peristalsis was low and that gastric mixing was confined in laminar regime. Further efforts are needed to investigate the role of other physiological processes such as gastric secretions and emptying in overall gastric mixing performance.

The present study aimed to evaluate the effect of the citric acid on the properties of solid pine wood, which were submitted to thermomechanical treatment. A preliminary test was performed in a previous study to evaluate the influence of different temperatures of pressing and concentrations of citric acid over the physical properties of wood. After choosing the best treatments (170°C and 5% and 10% of citric acid) it was evaluated the effect of these on the chemical properties (SEM, FTIR and pH), on the density profile using an X-ray microtomography, and on the resistance to ageing through abrasion test. The result of the chemical analysis allowed to observe an increase of the presence of ester functional groups, as well as a better coverage and higher acidity of the surface. The density profile technique allowed to observe the formation of peaks of density on the surface where the acid was applied. Lastly, it was also possible to verify an increase in the resistance to abrasion because of the application of the citric acid.

Background: Parathyroid imaging techniques are used in patients with biochemically confirmed primary hyperparathyroidism (pHPT) to detect the localization of enlarged parathyroid gland(s) (PTG) and thereby to allow more focused, unilateral or minimally invasive parathyreoidectomy (PTX), instead of classical bilateral neck exploration (BNE). Although the preferred sequence of imaging continues to evolve, ultrasonography (US) is usually the first line modality, followed by 99mTc sestamibi parathyroid scan (SPS). However, both tests may have suboptimal localizing accuracy with considerable rate of non-localized cases. Therefore, more accurate four-dimensional computed tomography scan (4D-CT) has been employed for PTG imaging. Currently, there is a paucity of data evaluating the utility of 4D-CT in low case-load settings. Aim: To evaluate the impact of PTG imaging, using 4D-CT in conjunction with it’s intraoperatively displayed results, on the outcomes of surgical PTX. Our primary outcome was sensitivity of 4D-CT in comparison to US and SPS for preoperative PTG adenoma localization. The secondary outcomes were the need for redo surgery and morbidity. Additionally, the characteristics of surgical PTX, i.e. operative time, number of removed parathyroid glands, and rate of simultaneous thyroid surgery, were assessed. Methods: A single-center retrospective analysis of surgically treated patients with pHPT from 01/2010 to 01/2021 was conducted. Evaluation of impact of the preoperative imaging modalities on the results of surgical treatment was carried out. Results: During the study period 290 PTX were performed, 45 cases were excluded due to surgery for secondary, tertiary or recurrent HPT, or due to use of alternative imaging techniques; the remaining 245 patients were included in the study. US was carried out for PTG imaging in 236 (96.3%), SPS in 93 (38.0%), and 4D-CT in 52 patients (21.2%). The use of 4D-CT was associated with a significantly higher rate of successful localization of enlarged PTG (49 cases, 94.2%) compared to US and SPS (74 cases, 31.4%, and 54 cases, 58.1%, respectively). We distinguished between three groups of patients based on preoperative imaging: 1) PTG lateralization via US or SPS in 106 (43.3%) cases, 2) precise localization of PTG via 4D-CT in 49 (20.0%) patients, and 3) in 90 cases (36.7%) PTG imaging failed to localize enlarged gland. The group of 4D-CT localization had significantly shorter operative time, lower rate of simultaneous thyroid resections, as well as lower rate of removal of ≥2 PTG, compared to the other groups. The 4D-CT imaging was also associated with the lowest perioperative morbidity and with the lowest median PTH in one month follow-up; however, compared to the other groups, these differences were statistically not significant. Implementation of 4D-CT (since 01/2018) decreased the need for redo surgery (from 11.5% to 7.3%), and significantly increased the annual case load of PTX at our institution (from 15.3 to 41.0), compared to the period before 4D-CT diagnostics. Conclusions: 4D-CT imaging enabled to precisely locate almost 95% of enlarged PTG in patients with pHPT. Accurate localization and intraoperatively displayed imaging results are useful guides for surgeons in making PTX a faster and safer procedure in a low volume center.

The dimensional effect of the accumulation of an electric charge with a density of up to 270 μF/g by the system of compacted zirconium dioxide nanoparticles during exposure in an electric field (5000 V/m) under normal physical conditions is determined. Based on a qualitative complex analysis of the forms of appearance of the effect, it is shown that the place of localization of different charge carriers is the surface of nanoparticles. The supposed mechanism of this effect is considered using the theory of dispersed systems, the band theory, and the theory of contact phenomena in semiconductors. It was concluded that this mechanism is due to the phenomenon of localization of electron-type charge nanoparticles in the near-surface zone of the material in contact with the adsorption ion atmosphere. This effect is relevant for modern nanoelectronics, microsystem technology, and printed electronics.

Three-dimensional transfer functions (3D TFs) are generally assumed to fully describe the transfer behavior of optical topography measuring instruments such as coherence scanning interferometers in the spatial frequency domain. Therefore, 3D TFs are supposed to be independent of the surface under investigation resulting in a clear separation of surface properties and transfer characteristics. In this paper we show that the 3D TF of an interference microscope differs depending on whether the object is specularly reflecting or consists of point scatterers. In addition to the 3D TF of a point scatterer, we will derive an analytical expression for the 3D TF corresponding to specular surfaces and demonstrate this as being most relevant in practical applications of coherence scanning interferometry (CSI). We additionally study the effects of temporal coherence and disclose, that in conventional CSI temporal coherence effects dominate. However, narrowband light sources are advantageous if high spatial frequency components of weak phase objects are to be resolved, whereas for low-frequency phase objects of higher amplitude the temporal coherence is less affecting. Finally, we present an approach that explains the different transfer characteristics of coherence peak and phase detection in CSI signal analysis.

An interesting anomaly of the diffusion process with an apparently negative diffusion coefficient defined through the mean-square displacement in a one-dimensional quantum molecular chain model is shown. Nevertheless, the system satisfies the H-theorem, so that the second law of thermodynamics is satisfied. The reason why the “diffusion constant” becomes negative is due to the effect of the phase mixing process, which is a characteristic result of the one-dimensionality of the system. We illustrate the situation where this negative “diffusion constant” appears.

This study presents an instant preview and analysis system implementation of intelligent stereo cameras (ISCs). A parameter optimization prototype adopted the instant preview and analysis system of the ISCs has been achieved the automatic alignment function, and obtained optimal stereo films with the automatic alignment function by adjusting gap and angle between dual cameras. The instant preview and analysis system of the ISCs with parameter optimization can enhance the quality of stereo films effectively and reduce filmed errors and save retouched cost and time in harsh filmed environment.

In this letter, it is proposed that cryogenic quantum bits could operate based on the nonlinearity due to the quantum capacitance of two-dimensional Dirac materials, and in particular graphene. The anharmonicity of a typical superconducting quantum bit is calculated and the sensitivity of quantum bit frequency and anharmonicty with respect to temperature are found. Reasonable estimates reveal that a careful fabrication process could reveal the expected properties, thus putting the context of quantum computing hardware into new perspectives.

We successfully fabricated Ag@Cu2O core-shell decorated on reduced graphene oxide (rGO) nanocomposites (ACRN) by a simple and convenient in situ substitution method. The properties of these ACRN with heterostructure layers were characterized by scanning and transmission electron microscopies and absorption spectroscopy. We used p-nitrophenol (4-NP) as a probe molecule to determine the chemical catalytic activity of the ACRN. Upon introduction of rGO, a high electron transfer efficiency was achieved; thus, the catalytic activity was improved significantly. Therefore, the ACRN exhibited significantly improved catalytic activity for the reduction of 4-NP and showed the high application value in the removal of toxic and harmful substances from water. In addition, the fabricated ACRN was used for the reduction of organic dyes and explosive pollutants to generate nontoxic products. Furthermore, the high charge redistribution and transfer among Ag, Cu2O and rGO in the ACRN induced the high catalytic reduction of organic pollutants, indicating the excellent potential of these materials for applications in water pollution treatment.

Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in alkaline medium. Their conversion to 5-substituted -hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted -aminoketones or a single -diketone. The new compounds were characterized by spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.

A newly synthesized upper rim azocalix[4]arene, namely, 5,11,17,23-tetra[(4-ethylacetoxyphenyl) (azo)]calix[4]arene, CA-AZ was fully characterized and its chromogenic and selective properties for anions are reported. The receptor is selective for the fluoride anion and its mode of interaction in solution is discussed. The kinetics of the complexation process was found to be very fast as reflected in the immediate color change observed with a naked eye resulting from the receptor-anion interaction. Emphasis is made about the relevance in selecting a solvent in which the formulation of the process is representative of the events taking place in the solution. The composition of the fluoride complex investigated by UV/VIS spectrophotometry, conductance measurements and titration calorimetry was 1:1 and the thermodynamics of complexation was determined. The fluoride complex salt was isolated, and a detailed investigation was carried out to assess its ability to remove CO₂ from the air. Recycling of the complex was easily achieved. Final conclusions are given.

Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, Glucagon-Like Peptide-1 Receptor Ag-onists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aimed to investigate how the GLP-1RA Exendin-4 (Ex-4) affects the mi-croRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from untreated, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment path-way analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, in-sulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigations.

CD44 has been known as a marker of tumor initiating cells, and plays pro-tumorigenic functions in many cancers. The splicing variants play critical roles in malignant progression of cancers by promoting the stemness, cancer cell invasion or metastasis, and resistance to chemo- and radiotherapy. To understand each CD44 variant (CD44v) function is essential to know the property of cancers and establishment of the therapy. However, the function of the variant 4-encoded region has not to be elucidated. Therefore, specific monoclonal antibodies (mAbs) against the variant 4 are indispensable for basic research, tumor diagnosis, and therapy. In this study, we established anti-CD44 variant 4 (CD44v4) monoclonal antibodies (mAbs) by immunizing mice with a peptide containing the variant 4-encoded region. We next performed flow cytometry, western blotting, and immunohistochemistry to characterized them. One of the established clones (C₄₄Mab-108; IgG₁, kappa) reacted with CD44v3-10-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44v3-10). The K_D of C₄₄Mab-108 for CHO/CD44 v3-10 was 3.4 × 10⁻⁷ M. In western blot analysis, C₄₄Mab-108 detected CD44v3-10 in the lysate of CHO/CD44v3-10 cells. Furthermore, C₄₄Mab-108 stained formalin-fixed paraffin-embedded oral squamous carcinoma tissues in immunohistochemistry. These results indicated that C₄₄Mab-108 is useful to detect CD44v4 in various applications.

The rapid emergence and worldwide detection of the SARS-CoV-2 omicron variant underscore the importance of robust genomic surveillance systems and prompt information sharing among global public health partners. The Omicron variant has rapidly replaced the delta variant as a dominating SARS-CoV-2 variant because of natural selection, favoring the variant with higher infectivity and more strong vaccine breakthrough ability. Also known as B.1.1.529, Omicron has four sub-variants, BA.1, BA.2, BA.3, and BA.4. Among them, BA.1 is the currently prevailing sub-variant, BA.2 is found to be able to alarmingly re-infect patients initially infected by omicron BA.1. BA.3 sub-variants is a combination of mutations of BA.1 and BA.2, especially in the spike protein. Today emerging is the BA.4, herein described and first detected in Italy, harboring a new mutation, specifically a deletion in the ORF 1 ab gene, corresponding to KSF141_del in non-structural protein 1 (nsp1), a critical virulence factor able to suppress host translation. The bioinformatics comparison analysis with the other three sub-variants pointed out that the deletion was not present previously and was never reported until now. Therefore, we can speculate that omicron BA.4; will become a new dominating “variant of concern” and might also break vaccine protection . On the other hand, we show that other proteins are mutated in the BA.4 in particular, seven mutations are recognized in the nucleocapsid (N) protein, the capability of five different types of rapid antigenic tests to recognize it.

Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity that in turn determines the tumor cell response towards therapeutic drugs. Sever-al lines of evidence suggest that therapeutic interventions foster the selection of drug resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melano-ma. Here we established a dual reporter system enabling the tracking of NGFR expression and mRNA stability, providing insights into the maintenance of NCSC-states. We observed that the transcriptional reporter that contained a 1kb fragment of the human NGFR promoter was acti-vated only in a minor subset (0.72±0.49%, range 0.3-1.5) and ~2-4% of A375 melanoma cells re-vealed stable NGFR mRNA. The combination of both reporters provided insights into pheno-type switching and revealed that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated genes serving as potential drivers of a NGFR-associated phenotype switching in vitro and in relapsed, post-BRAF inhibitor treated tu-mors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provided insights into plastici-ty and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

In this work, pure TiO₂ and binary nanocomposites of Fe₃O₄/TiO₂ and Ag/TiO₂ were synthesized in order to improve photocatalytic performance of these samples for degradation of 2, 4-dichlorophenol (2, 4-DCP) as an organic pollutant. A range of analytical techniques including XRD, DRS, SEM/EDX, and elemental mapping were employed to reveal the crystal structure, morphology and property of the nanocomposites. XRD data demonstrated that the prepared samples are purely in TiO₂ anatase phase and cubic spinel Fe₃O₄ exist in the synthesized nanocomposite. We calculated the TiO₂ crystal size from XRD patterns, in the range of 8.35-11.09 nm. The presence of Ag, Fe, O, and Ti atoms in the synthesized nanocomposites was confirmed by SEM/EDX. We obtained 30.43, 32.02 and 42.40 % degradation of 2, 4-DCP (100 ml 2, 4-DCP 40 ppm and 0.01 g catalyst) for pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively, after 180 min of irradiation under visible light. Similar conditions were employed for 2, 4-DCP degradation under UV irradiation, we obtained 53.05, 51.00 and 71.50 % degradation of 2, 4-DCP pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively. Thus, the synthesized binary nanocomposites exhibited higher photocatalytic activity compared to pure TiO₂ under visible light.

Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-regulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression, and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation up-regulates SOX2OT expression. This up-regulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ER stress reprogramming of breast cancer cells.

Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging, angiogenesis, and atherosclerosis-based cardiovascular disease (ACVD). Dipeptidyl peptidase-4 (DPP-4) is a complex enzyme (also called CD26) that acts as a membrane-anchored cell surface exopeptidase. DPP4 is upregulated in metabolic and inflammatory cardiovascular disorders. The widespread expression of DPP4 macrophages and immune cells and the noncatalytic function of DPP4 (also called CD26) as a signaling and binding protein across a wide range of species suggest a teleological role for DPP4 in inflammation and immune response. DPP-4 exhibits many physiological and pharmacological functions by regulating its extremely abundant substrates [e.g., stromal cell-derived factor-1α/ C-X-C chemokine receptor type-4, glucagon-like peptide-1 (GLP-1), etc.]. Over last ten year, emerging data demonstrated unexpected roles for GLP-1 and DPP-4 in extracellular and intracellular signaling, immune activation, inflammation, oxidative stress production, cell apoptosis, insulin resistance, and lipid metabolism,. This mini review has focuses on recent novel findings in this field, highlighting an imbalance between GLP-1 and DPP4 as a potential therapeutic molecular target in treatments of chronic psychological stress-related atherosclerotic cardiovascular disease in humans and animals.

The toxic effects of 4-octylphenol (4-OP) have been studied in species such as mouse and fish; however, the toxic effects of 4-OP in male specific niche cells has not been researched. In this study, we investigated the molecular mechanism of toxicity of 4-OP in mouse TM4 Sertoli cells. TM4 cells were treated with four concentrations (0, 10, 30, and 50 µM/mL) of 4-OP at time points 24, 48, and 72 h. Cell viability and apoptosis assay was conducted following exposure. 4-OP significantly decreased cell viability in a concentration- and time-dependent manner, and increased apoptosis. Quantitative PCR analysis showed that Bad, Bax, and Bak mRNA expression levels were higher in exposed cells than in the control, but Bcl-2 expression was decreased. Western blotting revealed that 4-OP induced activities of caspase-3 and phosphorylation of Bad in a concentration- and time-dependent manner. Additionally, cytochrome C protein did not colocalize with mitochondria marker dye by 24 h. Cytochrome c protein expression increased in a time-dependent manner with 50 µM/mL. These results suggest that 4-OP induces mitochondria-mediated apoptosis by regulation of Bcl-2 family proteins and caspase-3 activation in male Sertoli cells.

In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4 positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers was noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gallbladder) in comparison to primary tumors. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.

In this work, the solar light-induced redox photoactivity of the ZnO semiconductor material was used to prepare at room temperature CuxO-ZnO composite catalysts with a control of the chemical state of the copper oxide phase. The preparation of Cu2(I)O-ZnO and Cu(II)O-ZnO composite catalysts was achieved by using Cu(acac)2 in THF-water and Cu(NO3)2 in water as metallic precursor, respectively. Prior to the implementation of the photo-assisted synthesis method, the most efficient photoactive ZnO material was selected among different ZnO materials prepared by the low temperature polyol method and through the precipitation method with carbonates and carbamates as precipitation agent, by taking the photocatalytic degradation of the 4-chlorophenol compound in water under simulated solar light as model reaction. The ZnO support materials were characterized by XRD, BET, TGA, SEM and TEM, and the synthesis method was strongly influencing their photoactivity in terms of 4-chlorophenol degradation and of total organic carbon removal. The most photoactive ZnO material was prepared by precipitation with carbonates and calcined at 300°C, and was taking advantage of a high specific surface area and a small mean crystallite size for achieving a complete 4-chlorophenol mineralization within 70 min of reaction, with a minimum Zn2+ released to the solution due to surface photocorrosion. Beside thermal catalysis applications, this work opened a new route for the facile synthesis of Cu2O-ZnO heterojunction photocatalysts, that could take advantage under solar light of the heterojunction built between the p-type semi-conductor Cu2O with direct visible light band gap and the ZnO semiconductor phase.

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in human. The calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2 and EDs+ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in uterus. Whereas, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

Objective: Diabetes is associated with increased cardiovascular and cerebrovascular disease-related mortality. We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), total and active glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). Methods: This study consisted of four groups in Medicine Hospital between April- October, 2017: Control group (mean ages: 50.3 ± 10.7 years, 20 females and 15 males), diabetic group (DM) (mean ages: 53.9 ± 11.1, 14 females and 23 males), CAD group (mean ages: 62.6 ± 11.8, 17 females and 17 males) and CAD+ DM group: (mean ages: 62.6 ± 11.8 years, 18 females and 18 males). Results: Both CAD and CAD+DM groups have higher CIMT levels than controls. CAD+DM group have also significantly higher CIMT levels than DM group. Left external carotid artery (ECA) was only found different in DM group from controls. When compared with controls, DM, CAD groups have low DPP-4 and GLP-1_total concentration. Control group have significantly lower SFRP-4 levels than DM, CAD and CAD+DM (p<0.001) groups. Serum GLP-1_total levels were found to be significantly low in CAD+DM group when compared to control group. Conclusion: DPP-4 and SFRP-4 levels are predictive marker for atherosclerosis in diabetes, correlates well with HOMA-IR particularly in diabetes. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD. Large cohorts and at-risk populations are needed to confirm the predictive value of these findings.

Machinery degradation assessment can offer meaningful prognosis and health management in-formation. Although numerous machine prediction models based on artificial intelligence have emerged in recent years, they still face a series of challenges: (1) Many models continue to rely on manual feature extraction. (2) Deep learning models still struggle with long sequence prediction tasks. (3) Health indicators are inefficient for remaining useful life (RUL) prediction with cross-operational environments when dealing with high-dimensional datasets as inputs. This research proposes a health indicator construction methodology based on a transformer self-attention transfer network (TSTN). This methodology can directly deal with the high-dimensional raw dataset and keep all the information without missing when the signals are taken as the input of the diagnosis and prognosis model. First, we design an encoder with a long-term and short-term self-attention mechanism to capture crucial time-varying information from a high-dimensional dataset. Second, we propose an estimator that can map the embedding from the encoder output to the estimated degradation trends. Then, we present a domain dis-criminator to extract invariant features from different machine operating conditions. The case studies with the FEMTO-ST bearing dataset and the Monte Carlo method for RUL prediction during the degradation process are conducted. The experiment results fully exhibited the signif-icant advantages of the proposed method compared to other state-of-the-art techniques.

The three-dimensional morphology of frictional sub-surfaces holds significant importance for studying tribological issues. However, the uniformity of horizontal datum in 3D scanning is limited for curved surfaces, resulting in the inability to obtain accurate contour characterization parameters from the scanning results. This study aims to address this issue by constructing regular surface equations and normalizing the 3D profiler scanning results. By fitting the data, a "plane" surface representative of the surface features is obtained, and the paper demonstrates this approach on the surface morphology of different worn parts in the frictional area of spherical bearings located in the specific environment of the Three Gorges gate. The results indicate that the obtained "plane" effectively reconstructs the three-dimensional morphology map of the regular surface. Moreover, this reconstructed plane not only clearly illustrates the surface characteristics but also provides the foundation for analyzing the wear mechanism.

With advances in the development of autonomous vehicles (AVs), more attention has been paid to the effects caused by adverse weather conditions on them. It is well known that the performance of self-driving vehicles is reduced when they are exposed to stressors that impair visibility or generate water or snow accumulation on sensor surfaces. This paper proposes a model to quantify weather precipitation, such as rain and snow, perceived by moving vehicles based on outdoor data. The modelling covers a wide range of parameters, such as varying wind direction and realistic particle size distributions. The model allows the calculation of precipitation intensity on inclined surfaces of different orientations and on a circular driving path. The modelling results were partially validated against direct measurements carried out by a test vehicle. The model outputs showed strong correlation with the experimental data for both rain and snow. Mitigation strategies for heavy precipitation on vehicles can be developed and correlations between precipitation rate and accumulation level can be traced using the presented analytical model. Dimensional Analysis of the problem has highlighted the critical parameters that can help the design of future experiments. The obtained results highlight the importance of the angle of the sensing surface on the perceived precipitation level. The proposed model is used to analyze optimal orientations for minimization of the precipitation flux, which can help to determine the positioning of sensors on the surface of autonomous vehicles.

Misuse of measurement units and orientations leads to errors in scientific applications, Cyber Physical Systems (CPS), and IoT C/C++ programs. Standard type system are inadequate in preventing such errors. Although dimensional and orientational analysis in physics can manually detect these errors in equations, analyzing complex code with intricate physical computations is impractical. To overcome this challenge, we propose an advanced type system that incorporates units and orientations as integral components within a specialized type library. Our enhanced type system automatically detects potential errors during compile time by representing physical quantities as types and utilizing dimensional analysis, orientational analysis, and metaprogramming techniques. Our improved type system enables formal verification of C++ software, successfully verifying programs with extensive codebases. We also employ it for runtime verification of dynamic linking and pointer operations in C++ programs. The integration of compile-time verification, dimensional analysis, orientational analysis, and advanced type system enhances the robustness and accuracy of scientific applications, CPS, and IoT C/C++ programs. By leveraging these approaches, we ensure precise calculations and prevent errors related to measurement units and orientations, resulting in substantial improvements in reliability and accuracy.

In recent years, with the popularity of smart mobile devices, the interaction between devices and users, especially in the form of voice interaction, has become increasingly important. If smart devices can understand more users' emotional states through voice data, more customized services can be provided for users. This paper proposes a novel machine learning model for speech emotion recognition, which combines convolutional neural networks (CNN), long short-term memory neural networks (LSTM), and deep neural networks (DNN), called CLDNN. To make the designed system can recognize the audio signal closer to the human auditory system does, this article uses the Mel frequency cepstral coefficients (MFCCs) of audio data as the input of the machine learning model. First, the MFCCs of the voice signal is extracted as the input of the model, and the feature values of the data are calculated using several local feature learning blocks (LFLB) composed of one-dimensional CNN. Because the audio signals are time-series data, the feature values obtained from LFLBs then input into LSTM layer to enhance the learning on time-series level. Finally, fully connected layers are used for classification and prediction. Three databases RAVDESS, EMO-DB and IEMOCAP are used for the experiments in this paper. The experimental results show that the proposed method can improve the accuracy compared to other related researches in speech emotion recognition.

The advent of graphene opens up the research into two-dimensional (2D) material, which is considered as a revolutionary material in the future. Due to its unique geometric structure, graphene exhibits a series of exotic physical and chemical properties. Besides, single-element-based 2D materials (Xenes) have garnered tremendous interest. At present, 16 kinds of Xenes (silicene, borophene, germanene, phosphorene, tellurene, etc.) have been explored, mainly distributed in the third, fourth, fifth and sixth main groups. The current methods to prepare monolayer or few-layer 2D materials include epitaxy growth, mechanical exfoliation, and liquid phase exfoliation. Although two Xenes (aluminene and indiene) have not been synthesized due to the limitations of synthetic methods or stability of Xenes, other Xenes have been successfully realized by elaborately artificial design and synthesis. Focusing on elemental 2D materials, this review mainly summarizes the recently reported work about tuning the electronic, optical, mechanical, or chemical properties of Xenes via surface modifications achieved by controllable approaches (doping, adsorption, strain, intercalation, phase transition, etc.) to broaden the applications in various fields, including spintronics, electronics, optoelectronics, superconducting, photovoltaics, sensors, catalysis, and biomedicines. These advances in surface modification of Xenes have laid a theoretical and experimental foundation for the development of 2D materials and their practical applications in diverse fields.

This paper introduces a multi-class hand gesture recognition model developed to identify a set of defined hand gesture sequences in two-dimensional RGB video recordings. The work presents an action detection classifier that looks at both appearance and spatiotemporal parameters of consecutive frames. The classifier utilizes a convolutional-based network combined with a long-short-term memory unit. To leverage the need for a large-scale dataset, the model uses an available dataset to then adopt a technique known as transfer learning to fine-tune the model on the hand gestures of relevance. Validation curves performed over a batch size of 64 indicate an accuracy of 93.95% (± 0.37) with a mean Jaccard index of 0.812 (± 0.105) for 22 participants. The presented model illustrates the possibility of training a model with a small set of data (113,410 fully labelled frames). The proposed pipeline embraces a small-sized architecture that could facilitate its adoption.

The paper proposes a novel methodology for the stabilization of shallow foundations, with a simplified model combined with 3D Electrical resistivity tomography (ERT-3D) and conso- lidation injections. To determine its usefulness, the method has been applied in a case located in Estepona (southern Spain). The chosen tomography model is the dipole-dipole configuration, with an optimized distance between electrodes of 0.80 m for a better visualization of the foundation subsoil; with this parameterization, a total of 72 electrodes were installed in the analyzed case. In this work, the depth of the anomaly in the building's supporting subsoil was detected ranging from 2.00 m to 3.90 m deep. The study also delineates areas of high resistivity variations (50-1,000 Ω m) in the middle and eastern end of the field. These data have been validated and corroborated with a field campaign. The results of the ERT-3D monitoring are presented, once the investment data has been processed with the RES3DINV software, from the beginning to the end of the stabilization intervention. The novelty occurs with the interaction between the tomography and the foundation consolidation injections, until the final stabilization; very useful methodology in case of emergency consolidation, where there is a need to minimize damage to the building. Thus, people using this combined system; will be able to practically solve the initial anomalies of the subsoil that caused the damages, in a non-invasive way, considerably lowering the value of the resistivities.

Black poplar (Populus nigra L.) was thermally modified in nitrogen atmosphere. Treatment in nitrogen atmosphere can improve the dimensional stability of black poplar. The effects of the modification process on poplar wood were evaluated for temperatures: 160 °C, 190 °C, and 220 °C applied for 2 h; and 160 °C and 190 °C for 6 h. The percentual impact of temperature and time of modification on the properties of modified wood was analysed. The study permitted to identify correlations between the chemical composition and selected physical properties of thermally modified poplar wood. The dimensional stability of poplar wood improves after thermal modification in nitrogen. The higher the temperature of modification, the lower the equilibrium moisture content (EMC) of black poplar. At the temperature of 220 °C, EMC was two times lower than the EMC of non-modified black poplar. It is also possible to reduce the dimensional changes of wood two-fold (at the modification temperature of 220 °C), both in radial and tangential directions, independently of the acclimatisation conditions (from 34% to 98% RH). Similar correlations have been found for wood that has been soaked in water. Higher modification temperatures and longer processing times contributed to a lower swelling anisotropy (SA).

This Letter revisits the instability of jet produced by shaped charge. Scaling laws for shaped charge jet are derived by dimensional analysis. It shows that the scaling laws are universal when cross-sectional shrinkage rate is not included in the formulation.

There exist numerous high-dimensional problems in the real world which cannot be solved through the common traditional methods. The metaheuristic algorithms have been developed as successful techniques for solving a variety of complex and difficult optimization problems. Notwithstanding their advantages, these algorithms may turn out to have weak points such as lower population diversity and lower convergence rate when facing complex high-dimensional problems. An appropriate approach to solve such problems is to apply multi-agent systems along with the metaheuristic algorithms. The present paper proposes a new approach based on the multi-agent systems and the concept of agent, which is named Multi-Agent Metaheuristic (MAMH) method. In the proposed approach, several basic and powerful metaheuristic algorithms, including Genetic Algorithm (GA), Particle Swarm Optimization (PSO), Artificial Bee Colony (ABC), Firefly Algorithm (FA), Bat Algorithm (BA), Flower Pollination Algorithm (FPA), Gray Wolf Optimizer (GWO), Whale Optimization Algorithm (WOA), Crow Search Algorithm (CSA), Farmland Fertility Algorithm (FFA), are considered as separate agents each of which sought to achieve its own goals while competing and cooperating with others to achieve the common goals. In overall, the proposed method was tested on 32 complex benchmark functions, the results of which indicated effectiveness and powerfulness of the proposed method for solving the high-dimensional optimization problems. In addition, in this paper, the binary version of the proposed approach, called Binary MAMH (BMAMH), was executed on the spam email dataset. According to the results, the proposed method exhibited a higher precision in detection of the spam emails compared to other metaheuristic algorithms and methods.

ARBTools is a Python library containing a Lekien-Marsden type tricubic spline method for interpolating three-dimensional scalar or vector fields presented as a set of discrete data points on a regular cuboid grid. ARBTools was developed for simulations of magnetic molecular traps, in which the magnitude, gradient and vector components of a magnetic field are required. Numerical integrators for solving particle trajectories are included, but the core interpolator can be used for any scalar or vector field. The only additional system requirements are NumPy.

In the process of sustainable development in the future, human society faces problems such as severe population load, economic transition, and lack of educational measures. One of the root causes of these problems is the shortage of innovative talents. Therefore, how to cultivate learners with multi-disciplinary integration and innovation ability is the key point that should be paid attention to in promoting the concept of quality education and coping with the future sustainable development process. This paper uses questionnaire survey method and literature analysis method to analyze the development of many educational institutions with STEAM concept as the core in China since 2017. It is found that the existing STEAM educational institutions generally have the following problems: the lack of team composition、difficulty in independent research and development、single course content and insufficient validation of course effectiveness. In order to more effectively promote the sustainable development of China's future course, STEAM education institutions should focus on strengthening the following development strategy: gradient team building, continuous independent research and development, cutting-edge projects curriculum transformation mechanism and multi-angle course effectiveness verification.

Three-dimensional (3D) imaging has attracted more and more interests because of its widespread applications, especially in information and life science. These techniques can be broadly divided into two types: ray-based and wavefront-based 3D imaging. Issues such as imaging quality and system complexity of these techniques limit the applications significantly, and therefore many investigations have focused on 3D imaging from depth measurements. This paper presents an overview of 3D imaging from depth measurements, and provides a summary of the connection between these the ray-based and wavefront-based 3D imaging techniques.

In this work, we report the fabrication of the new heterojunction of two 2D hybrid layered semiconductors, ZnO(stearic acid)/V₂O₅(hexadecylamine), and its behavior in the degradation of aqueous methylene blue under visible light irradiation. The optimal photocatalyst efficiency, reached at a ZnO(stearic acid)/ V₂O₅(hexadecylamine) ratio of 1:0.25, results to be about six times higher than that of pristine zinc oxide. Reusability test shows that after three photocatalysis cycles no significant changes in neither the dye degradation efficiency loss nor photocatalyst structure occur. Visible light photocatalytic performance observed indicates there is synergetic effect between both 2D nanocomposites used in the heterojunction. The visible light absorption enhancement promoted by the narrower bandgap V₂O₅ based components; an increased photo generated charge separation favored by extensive interface area; and abundance of hydrophobic sites for dye adsorption appear as probable causes of the improved photocatalytic efficiency in this hybrid semiconductors heterojunction. Estimated band-edge positions for both conduction and valence band of semiconductors together with experiments using specific radical scavengers allow a plausible photodegradation mechanism.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Aquaporin-4 (AQP4) expression is associated with development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells were overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (600), with other genes such as Gpnmb, Itgax, Cd68 and Atp6v0d2 also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and absence of AQP4 prolonged its expression in this tissue.

The relationship between nations is largely seen as a peripheral issue in the recent history of political philosophy and in the majority of discussions of political philosophy issues today. The idea of a universal natural state were countries are seen as essentially self-sufficient, functional units, and have been proposed to represent the relative lack of moral standards guiding relationships between nations. At one extreme of the tradition, international thought has substituted raison d'état being the highest norm for any universal laws governing relations between states, a view embodied by Machiavelli, Rodin, and others and Hobbes , The lack of supranational political powers has led to the conclusion that, even in cases where the possibility of international moral relationships has been acknowledged, such as in post-Grotian publications on international law, these ties are significantly weaker than in-tranational social bonds. The justification and aversion to war—the primary mode of social in-teraction in the natural condition of the world—is the only issue in the field of global relations to have received substantial theoretical study. Even though this disregard was justified in the past, a number of recent events force us to re-consider the "recalcitrance of international affairs to being theorized about."2. The growing gap between both prosperous and impoverished nations; the emergence of centers of economic in-fluence beyond the reach of effective state regulation; the emergence of severe food and energy shortages brought on, at least in part, by national governments' pursuit of disorganized and uncontrolled growth policies; the growing sensitivity of domestic Countries to the outside eco-nomic, political, and cultural events are some of these developments , requests from third-world nations for greater equal access to international politics and economy. To put it in terms more familiar to conversations about this topic, the rise of "low politics" in negotiation and "welfare questions" within global forums corresponds with the growing influence of transnational con-nections and international agreements on human well-being. Not because "high politics"—that is, the threat and prevention of war—has lost significance; rather, it is just one issue among many for which international cooperation is now required in order to find answers.

Autism has been described as a gastrointestinal and neurological condition that is represented by impairments in language and social situations. Recently reported increases in the occurrence of Autism Spectrum Disorder (ASD) have resulted in increased research into the environmental differences between areas with a high occurrence, as in the “Western” diet populations, and a more locally derived diet population, wherein the rate appears to be significantly less. Thirty autistic children (USA) ages 6 to 21, were sampled at three different intervals: prior to any intervention, post-xylitol intervention, and post-probiotic intervention. The sampling consisted of buccal swabs for MITOSWAB testing, and saliva for metatranscriptomics to determine the entire range of microorganisms and the metabolome. In addition, a “Blue Zone” subject component that included 30 Colombian children, ages 6-16, and who were healthy and within normal behavior standards, also had buccal swabbing and salivary sampling performed for comparison along with 30 healthy (no history medications, illnesses, or behavior issues) USA children matched for age and gender. Saliva samples were analyzed metatranscriptomically and artificial intelligence was utilized to discern important differences in the microbiome that included bacteria, archaea, fungi, and viruses, and microbial functions. Significant differences were noted, and seen in the temporal data, demonstrating shifts that may have been precipitated by the interventions, with both the probiotics and the polyols. Particular bacterial strains were significantly more prevalent in the autism subject group including a strain that reduces neurotransmitters by enzymatic degradation. This provided supporting evidence to the hypothesis that the occurrence of autism may also be influenced by low Gamma Amino Butyric Acid (GABA) levels during development. Also, of interest was the un-expected finding that verbal skills dramatically increased in 6 of the 30 ASD subjects following xylitol supplementation.

Metabolomics profiling for accurate and reliable quantification of organic acids that carry a carboxylic acid functional group in complex biological samples, remains a major analytical challenge in clinical chemistry research. Several procedural barriers associated with quantification of clinically important carboxylic containing metabolites (CCMs) including spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column, limit the sensitivity, specificity, and reproducibility of multiple-reaction monitoring (MRM) based LC-MS assay development. We report a targeted metabolomics-based analytical method for the quantification of CCMs using phenylenediamine derivatization. Accurate and sensitive quantification of CCMs is successfully demonstrated in an array of biological matrices. Recovery of metabolites from different matrices (plasma, serum, urine, saliva, tissues, and cell extracts), ranged from 90% to 105%, with all the CVs ≤ 10%. The method showed linearity over a broad dynamic range from 0.1 ng/mL to 10 µg/mL with linear regression coefficients of 0.99 for most of the metabolites tested herein, that covers broad-based applicability with the analysis of biological samples. In most cases the LODs were as low as 0.01 ng/mL. The phenylenediamine-based derivatization of carboxyl acid library consisting of more than 70 endogenous metabolites was constructed for metabolite identification, which spanned more than 40 biological pathways. The library included a wide-variety of structurally variant CCMs such as amino acids/conjugates, short to medium chain organic acids, di/tri-carboxylic acids/conjugates, fatty acids and some ring-containing CCMs. We compared the CCMs profiles of pancreatic cancer cells with normal pancreatic epithelial cells to test and validate the biological utility of this method. The comparative profiling between cancerous and normal cells resulted in the identification of potential biomarkers in pancreatic cancer, and their correlation with several key metabolic pathways such as central carbon energy metabolism, protein metabolism, including TCA cycle, glycolysis, Gln-Glu pathway, and biosynthesis of amino acids and unsaturated fatty acids was established. The method, described herein, for the first time enables the sensitive and highly specific quantification of CCMs on small sample size with high reproducibility in a high throughput manner. Given the biological and functional significance of this class of metabolites, this mass spectrometry based targeted quantitative assay, fills an important gap and is likely to support a wide range of applications for basic, clinical, and translational research.

The reactivity of 3,5-di-(pyridin-4-yl)-1,2,4-thiadiazole (L1) with 1,4-diiodotetrafluorobenzene (1,4-DITFB) was explored and the halogen-bonded 1:1 co-crystal (1) was successfully isolated and structurally characterized.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise, and highly accurate for the measurement of the drug and the mains metabolites. The lower limit of quantification resulted 1 ng/mL. The curve range of 1-500 ng/mL and 50-2000 ng/mL, for plasma and tumor homogenate respectively, was appropriate for the analysis, as demonstrated by the accuracy between 96.8% and 102.4% for plasma and 96.6-102.3% for tumor. The inter-days precision and accuracy determined on quality controls at 3 different levels were in ranges of 6.9%-7.5% and 99.3-101.0% and 0.96-1.91% and 102.3-105.8% for plasma and tumour, respectively.

Boeremia exigua var. exigua is a recurrent pathogen causing root rot in industrial chicory. Currently, there is no chemical or varietal control for this disease, and thus management strategies need to be developed. This study determined the biocontrol effect of strains of Pseudomonas protegens bacteria with antimicrobial compounds on the fungus B. exigua var. exigua under in vitro, in vivo and field conditions. In addition, root colonization by these bacteria was estimated by molecular analysis. Eighteen isolates of Pseudomonas spp were evaluated and the strains that showed the greatest in vitro inhibition of fungal mycelial growth (mm), Ca10A and ChB7, were selected. Inoculation with the strain ChB7 showed less severity (necrotic area) under in vivo conditions (root trials) compared to the control inoculated with the pathogen (P≤0.05). The molecular analysis revealed that root colonization of plants grown in pots was equal or greater than 70%. Similar levels were observed in the field trials conducted in Selva Negra and Canteras experimental stations (2015-16 season), with values ranging from 85.7 to 70.5% and from 75.0 to 79.5%, respectively. Regarding yield (ton ha-1), values were higher in the treatments inoculated with strains Ca10A and ChB7 (P≤0.05) in both experimental sites, while a lower incidence and severity of root rot were observed in Selva Negra. These results suggest that the Chilean strains of P. protegens are a promising tool for the control of root diseases in industrial chicory.

The prevalent pathogens associated with bovine uterine infections are bacteria that appear to increase the host's susceptibility to secondary infections with other bacteria or viruses, among which BoHV-4 is the most frequently found. In this work, the study of the pathways of apoptosis induction was carried out on an experimental model of primary culture of endometrial cells, in order to know the implication of BoHV-4 and the presence of bacterial LPS in the pathogenesis of the bovine reproductive tract. For this, different staining techniques and molecular analysis by RT-PCR were used. The results obtained allowed us to conclude that the level of cell death observed in the proposed primary culture is directly related to the time of viral infection and the presence of LPS in BoHV-4 infection. The apoptosis indices in cells infected with BoHV-4, BoHV-4 + LPS presented a maximum that correlates with the appearance of the cytopathic effect, and the maximum viral titers in the model studied. However, morphological, biochemical and molecular changes were evident during both early and late stages of apoptosis. These findings provide information on the factors that may influence the pathogenesis of BoHV-4 and help to better understand the mechanisms involved in virus infection.

Norovirus (NoV) is recognised as a major cause of epidemic and sporadic acute gastroenteritis (AGE) in all age groups. Information on the genetic diversity of the NoVs circulating in the 1980s and 1990s, before the development and adoption of dedicated molecular assays, is limited compared to the last decades. In the period 1986-2020, uninterrupted viral surveillance was conducted in symptomatic children hospitalized for AGE in Palermo, Italy, providing a unique time capsule for exploring the epidemiological and evolutionary dynamics of enteric viruses. In this 35-year long time span NoVs of genogroup II (GII) were detected in 15.6% of AGE requiring hospitalization, whilst GI NoVs in 1.4%. Overall, the predominant NoV capsid (Cap) genotype was GII.4 (60.8%), with temporal replacement of the GII.4 Cap variants and associated polymerase (Pol) types. The chronology of emergence and circulation of the different GII.4 variants were consistent with the data available in literature. Also, for GII.3 and GII.2 NoVs the circulation of different lineages/strains, differing in either the Cap or Pol genes or in both, was observed. This long-term study revealed the ability of NoVs to modify continuously and rapidly their genomic makeup and highlights the importance of surveillance activities for vaccine design.