We prove an analog of the removable singularity theorem for bounded harmonic functions on stratified sets. The harmonic functions are understood in the sense of the soft Laplacian. The result can become one of the main technical components for extending the well-known Poincaré–Perron’s method of proving the solvability of the Dirichlet problem for the soft Laplacian.

In this paper, a method is developed for presenting a novel virtual torque sensor based on precise model and position measurements avoids the need of traditional strain gauges and amplifiers. More specifically, the harmonic drive compliance model and the Gaussian process regression (GPR) technique are used together to achieve virtual torque sensor measurement. While the harmonic drive compliance model provides the analytic part, the Gaussian process regression method is used to reconstruct the unmolded part based on motor-side and link-side joint angles as well as motor current. After an automatic offline calibration, the method allows for a lean online implementation. The virtual torque sensor measurement is compared with measurements of a commercial torque sensor, and the results have attested the effectiveness of the proposed method.

The theory of harmonic based function is discussed here within the framework of umbral operational methods. We derive a number of results based on elementary notions relying on the properties of Gaussian integrals.

As known all physical properties of solids are described well by the system of quantum linear harmonic oscillators. It is shown in the present paper that the system consisting of classical linear harmonic oscillators having temperature dependent masses or (and) frequencies has the same partition function as the system consisting of quantum linear harmonic oscillators having temperature independent masses and frequencies while the means of the square displacements of the positions of the oscillators from their mean positions for the system consisting of classical linear harmonic oscillators having: the temperature dependent masses; temperature dependent frequencies; and temperature dependent masses and frequencies differ from each other and from that of the system consisting of quantum linear harmonic oscillators, and hence, the system consisting of classical linear harmonic oscillators describes well the thermodynamic properties of the system consisting of quantum linear harmonic oscillators and solids.

This research presents a novel algorithmic implementation to improve the analysis of visually controlled interception and accompanying motor action through the computational application of harmonic ratios and stimulation invariants. Unlike traditional models that focus mainly on psychological aspects, our approach integrates the relevant constructs into a practical mathematical framework. This allows for dynamic prediction of interception points with improved accuracy and real-time perception-action capabilities, essential for applications in neurorehabilitation and virtual reality. Our methodology uses stimulation invariants as key parameters within a mathematical model to quantitatively predict and improve interception outcomes. The results demonstrate the superior performance of our algorithms over conventional methods, confirming their potential for ad-vancing robotic vision systems and adaptive virtual environments. By translating complex theo-ries of visual perception into algorithmic solutions, this study provides innovative ways to im-prove motion perception and interactive systems. This study aims to articulate the complex inter-play of geometry, perception, and technology in understanding and utilizing cross-ratios at infin-ity, emphasizing their practical applications in virtual and augmented reality settings.

We investigate solutions of the classical Mathieu-Hill (MH) equation which characterizes the dynamics of trapped ions, based on the Floquet theory and starting from a well known analytical model. The analytical model we introduce demonstrates that the equations of motion are equivalent to those of the harmonic oscillator (HO). Two independent approaches are used, based on two classes of complex solutions of the MH equation. The paper addresses both the damped HO and parametric oscillator (PO) for an ion confined in an electrodynamic (Paul) trap. Stability and instability regions for the periodic orbits associated to the MH equation which describes a HO (PO) confined in an electrodynamic trap are also discussed, depending on the values of the Floquet exponent, for very small values of the $q$ parameter. The main objective of the paper is to identify stable and bounded solutions for the dynamics of a HO levitated in an electrodynamic trap. This paper represents a follow-up of a recently published article in Photonics, 11 (6) 551.

Gravity forward modeling as a basic tool has been wildly used to topography correction and 3D density inversion. The source region is usually discretized into tesseroid (i.e., spherical prism) to consider the influence of the curvature of planets in global or large-scale problems. Traditional gravity forward modeling methods in spherical coordinates, including the Taylor expansion and Gaussian-Legendre quadrature, are all based on spatial domain, which are mostly low computational efficiency. This study proposes a high-efficient forward modeling method of gravitational fields in spherical harmonic domain, in which the gravity anomalies and gradient tensors can be expressed as spherical harmonic synthesis form of spherical harmonic coefficients of 3D density distribution. A homogeneous spherical shell model has been used to test its effectiveness compared with traditional spatial domain methods. It demonstrates that the computational efficiency of the proposed spherical harmonic domain method has improved by four orders of magnitude and with a similar level of computational accuracy compared with the optimized 3D GLQ method. Finally, the proposed forward method is applied to topography correction of the Moon. The results show that the gravity response of the topography by our method is close to that of the optimized 3D GLQ method, and is also consistent with previous results.

Many natural signals exhibit a quasi-periodic behavior and are conveniently modeled as a combination of several harmonic sinusoids whose relative frequencies, magnitudes and phases vary with time. The waveform shape of those signals reflects important physical phenomena underlying their generation, which requires that those parameters be accurately estimated and modeled. In the literature, accurate phase estimation and modeling has received much less research effort than frequency estimation, or magnitude estimation. First, this paper addresses accurate DFT-based phase estimation of individual sinusoids in six scenarios involving two DFT-based filter banks and three different windows. It is shown that bias in phase estimation is less than 1E-3 radians when the SNR is equal to or larger than 2.5 dB. Taking as a reference the Cramér-Rao Lower Bound, it is shown that one particular window offers a performance of practical interest by approximating better the CRLB when signal conditions are favorable, and by minimizing the performance deviation when signal conditions are adverse. Second, this paper explains how a shift-invariant phase-related feature can be devised that characterizes harmonic phase structure, which motivates a signal processing paradigm that greatly simplifies parametric modeling, transformation and synthesis of harmonics signals, in addition to facilitating the understanding and reverse engineering of the phasegram. Theory and results are discussed in a reproducible perspective using dedicated experiments that are supported with code allowing not only to replicate figures and results in this paper, but also to expand research.

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

We discuss in detail a well known method for obtaining the frequencies of the normal modes of coupled harmonic oscillators that is based on the simultaneous diagonalization of two symmetric matrices. We apply it to some simple illustrative examples recently chosen for the presentation of an alternative approach based on a set of constants of the motion. We show that the traditional method is simpler, even in the case of equal frequencies. We also discuss a problem that commonly appears in elementary courses on quantum mechanics that also requires the diagonalization of two symmetric matrices.

This Article demonstrates how an eigendecomposition problem is inputted into a quantum circuit, how gates are applied in the quantum circuit, and how the output measurements are the correct eigenvalues. This process is known as quantum phase estimation (QPE). A quantum harmonic oscillator example, a foundational quantum physical chemistry problem, is demonstrated within the context of QPE. A particle in a box example, another quantum physical chemistry problem, may be solved by QPE with a caveat. These examples are of the limiting cases of diagonal matrices. Future advances in taking matrix inverses for solving linear sets of equations or finding ground state energies in the Schrödinger equation will use the principles implemented in this Article.

The Harmonic Graphs Conjecture states that there exists an asymptotic relation involving the Harmonic Index and the natural logarithm as the order of the graph increases. This conjecture, grounded in the novel context of Prime Graphs, draws upon the Prime Number Theorem and the sum of divisors function to unveil a compelling asymptotic connection. By carefully expanding the definitions of the harmonic index and the sum of divisors function, and leveraging the prime number theorem's approximations, we establish a formula that captures this intricate relationship. This work is an effort to contribute to the advancement of graph theory, introducing a fresh lens through which graph connectivity can be explored. The synthesis of prime numbers and graph properties not only deepens our understanding of structural complexity but also paves the way for innovative research directions.

This research will examine the computational methods to calculate the nonlinear optical process of second harmonic generation (SHG) that will be hypothesized to be present during lithium ion insertion into silicon nanowires. First it will be determined whether the medium in which SHG is conveyed is non-centrosymmetric or whether the medium is inversion symmetric where SHG as a part of the second-order nonlinear optical phenomenon does not exist. It will be demonstrated that the main interaction that determines SHG is multiphoton absorption on lithium ions. The quantum harmonic oscillator (QHO) is used as the background that generates coherent states for electrons and photons that transverse the length of the silicon nanowire. The matrix elements of the Hamiltonian which represents the energy of the system will be used to calculate the probability density of second-order nonlinear optical interactions which includes collectively SHG, sum-frequency generation (SFG) and difference-frequency generation (DFG). As a result it will be seen that at varies concentrations of lithium ions (Li+) within the crystallized silicon (c-Si) matrix the second-order nonlinear optical process has probabilities substantial enough to create second harmonic generation that could possibly be used for such applications as second harmonic imaging microscopy.

In this paper, we consider the relation of more than four harmonic points in a line. For this purpose, starting from the dependence of the harmonic points, Desargues’ theorems, and perspectivity, we note that it is necessary to conduct a generalization of the Desargues’ theorems for projective complete n-points, which are used to implement the definition of the generalization of harmonic points. We present new findings regarding the uniquely determined and constructed sets of H-points and their structure. The well-known fourth harmonic points represent the special case (n=4) of the sets of H-points of rank 2, which is indicated by P42.

In reservoir engineering, one of the main sources of information for the characterization of reservoir and well parameters is well testing. Among the unconventional well testing methodologies, Harmonic Well Testing (HPT) is appealing from an economic standpoint because it could provide well performance and reservoir behavior monitoring without having to interrupt field production. Recorded pressure analysis is performed in the frequency domain by adopting a derivative approach similar to conventional well testing. To this end, pressure and rate data must be decomposed into harmonic components. Test interpretability can be significantly improved if pressure data are detrended prior to interpretation, filtering out non periodic events such as discontinuous production from neighboring wells and flow regime variations which did not respect the designed test periodicity. Therefore, detrending offers the possibility of overcoming the limitation of HPT applicability due to the difficulty of imposing a regularly pulsing rate for the whole test duration (typically lasting several days). This makes HPT attractive for well performance monitoring, especially in gas storage fields. In this paper, the application of different detrending methodologies to synthetic HPT pressure data generated in different reservoir and operational scenarios is presented and discussed. Moreover, a real case application is also presented.

Metasurfaces of gold (Au) nanoparticles on a SiO2-Si substrate were fabricated for the enhancement of second harmonic generation (SHG) using electron beam lithography and lift-off. Triangular Au nanoprisms which are non-centro-symmetric and support the second- order non-linearity were examined for SHG. The thickness of the SiO2 spacer is shown to be an efficient parameter to spectrally tune to maximise SHG. Electrical field enhancement at the fundamental wavelength was shown to define the intensity of the second harmonics. Numerical modeling of light enhancement was verified by experimental measurements of SHG and reflectivity spectra at the normal incidence. At the plasmonic resonance, SHG is enhanced up to ∼3.5×103 times for the optimised conditions.

In this work we present the results obtained with an artificial neural network (ANN) which we trained to predict the expected output of high-order harmonic generation (HHG) process, while exploring a multi-dimensional parameter space. We argue on the utility and efficiency of the ANN model and demonstrate its ability to predict the outcome of HHG simulations. In this case study we present the results for a loose focusing HHG beamline, where the changing parameters are: the laser pulse energy, gas pressure, gas cell position relative to focus and gas cell length. The physical quantity which we predict here using ANN is directly related to the total harmonic yield in a specified spectral domain (20-40 eV). We discuss the versatility and adaptability of the presented method.

The article is devoted to biological models using recurrence sequences, which are connected with the harmonic progression 1, 1/2, …, 1/n, and some cooperative properties of genomes. The harmonic progression is itself one of the recurrence sequences based on the harmonic mean. This progression appears in the hyperbolic rules of oligomer cooperative organization in eukaryotic and prokaryotic genomes. This allows thinking that the harmonic progression is also related to inherited physiological systems, which must be structurally consistent with the genetic coding system for their transmission to descendants and survival in evolution. The harmonic progression is one of historically known mathematical series, whose features were studied by Pythagoras, Leibniz, Newton, Euler, Fourier, Dirichlet, Riemann. It is widely used in many known algorithms and is closely related to some other important mathematical objects, for example, the function of the natural logarithm and harmonic numbers. Accordingly, the article describes the possibilities of using these interrelated mathematical objects to model biological structures, including logarithmic spirals and some other. Modeling inherited spiral configurations seems to be a particularly urgent task, since they are extremely common at all levels of organization of living bodies and, according to Goethe, are lines of life. The principle of a recurrence similarity, that is a special similarity of parts and transformations presented in recurrence sequences of numbers and matrix operators (the scale similarity and scale transformations are only particular cases of such similarity), is considered as one of the key principles of structural organization of living bodies.

Active flow control of canonical laminar separation bubbles by steady and harmonic vortex generator jets (VGJs) was investigated using direct numerical simulations. Both control strategies were found to be effective in controlling the laminar boundary-layer separation. However, the present results indicate that using the same blowing amplitude, harmonic VGJs were more effective and efficient in reducing the separated region than the steady VGJs considering the fact that the harmonic VGJs use less momentum than the steady case. For steady VGJs, longitudinal structures formed immediately downstream of injection location led to formation of hairpin-type vortices causing an earlier transition to turbulence. Symmetric hairpin vortices were shown to develop downstream of the forcing location for the harmonic VGJs as well. However, the increased control effectiveness for harmonic VGJs flow control strategy is attributed to the fact that shear-layer instability mechanism was exploited. As a result, disturbances introduced by VGJs were strongly amplified leading to development of large-scale coherent structures, which are very effective in increasing the momentum exchange, thus, limiting the separated region.

To study the coupling mechanism and dynamic response of the end-face movable gear trans-mission system under complex excitation, a specific configuration of end-meshing movable gear reduction mechanism was used to achieve predetermined rigid thrust transmission and mis-matched gear meshing functions, which solved the inherent defects of traditional harmonic gear mechanism thin-wall flexible wheel easy to be damaged by fatigue. Considering the phenomenon of elastic deformation of live teeth accompanied by significant changes in meshing characteristics in the transmission process of end-meshing harmonic reducer, the influence of dynamic meshing parameters, live tooth deformation, time-varying stiffness of tooth meshing, and time-varying backlash on nonlinear dynamic performance was explored, as well as the mechanism of mul-ti-parameter coupling on transmission performance. The nonlinear dynamics model of the end-meshing harmonic reducer is established to solve the chattering prediction problem. Finally, a comprehensive test bed for the transmission system of harmonic reducer with meshing type with adjustable characteristic end was built to verify the correctness of the theoretical model and provide the theoretical and technical basis for exploring the optimal parameter selection of pas-sive vibration suppression problem.

In the present paper, we introduced and study a new class of harmonic univalent functions on unit disc U. also we obtain coefficient conditions, extreme points, convolution condition for the above class of harmonic univalent functions.

Harmonic resonances are part of the Power Quality (PQ) problems of electrified railways and have serious consequences for the continuity of service and integrity of components in terms of overvoltage stress. The interaction between Traction Power Stations (TPSs) and trains that causes line resonances is briefly reviewed showing the dependence on infrastructure conditions. The objective is real-time monitoring of resonance conditions seen first of all from the onboard panto-graph interface, but it is equally applicable at TPS terminals. Voltage and current spectra, and de-rived impedance and power spectra, are analyzed proposing compact and efficient methods based on Short-Time Fourier Transform, suitable for real-time implementation with the hardware avail-able for energy metering and harmonic interference monitoring. The methods are tested by sweeping long recordings taken at some European railways, covering cases of longer and shorter supply sections, with a range of resonance frequencies of about one decade. They give insight into the spectral behavior of resonances, their dependency on position and change over time, and criteria to recognize genuine infrastructure resonances from rolling stock emissions.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

We discuss a formalism which allows for the calculation of a higher harmonic current response to an applied electric field for disordered superconducting systems described on the basis of tight-binding models. The theory is based on an expansion of the density matrix in powers of the field amplitudes where we solve the equation of motion for the individual components. This allows the evaluation of higher order response functions on significantly larger lattices than one can achieve with a previously used approach, which is based on a direct temporal integration of the equation of motion for the complete density matrix. In case of small lattices, where both methods can be applied by including also the contribution of collective modes, we demonstrate the agreement of the corresponding results.

Background: During pregnancy, major physiological changes occur in every system. Understanding the hemodynamic changes in different stages of pregnancy can help to identify abnormal states during pregnancy. Harmonic analysis could be a useful tool in monitoring the state of the ventricular-arterial system during pregnancy. The aim of this study was to investigate the specific statistical relationships between changes in harmonic indices during different stages of pregnancy. Methods: A Total of 380 women (190 pregnant women and 190 age-matched non-pregnant women), with ages ranging from 20 to 45, were enrolled in the study. The visit measured the subject’s hemodynamic parameters including heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and photoplethysmography (PPG). SBP and DBP were evaluated by an automatic blood pressure monitor. PPG signal were continuously recorded for 12-seconds using a PPG sensor. Spectrum analysis of the PPG signal was performed to evaluate the first five harmonic components (C1 – C5) and harmonic phases (P1 – P5). Result: A comparison between pregnant women and non-pregnant women showed that the non-pregnant women had lower DBP, C3, C5 and P5 (p<0.05). Waist Circumference, Heart rate, C2, C4 and P2 were higher in pregnant women. Logistic regression analysis was used to determine the associations between pregnancy and harmonics indices. C2, C4 and P3 were positively and P1 and P4 were negatively associated with pregnancy after controlling age, BMI, waist circumference, heart rate, SBP and DBP. Conclusion: The results of this study provide information on the changes in the harmonic frequency components during various stages of pregnancy. The harmonic components of the PPG signal have independent predictive value for changes in a woman's physiology during pregnancy. Since non-invasive PPG measurements can be performed frequently and easily, in the future, it is possible that the hemodynamic changes from some pregnancy-related disorders could be studied by harmonic analysis.

Spherical harmonic (SH) interpolation is a commonly used method to spatially up-sample sparse Head Related Transfer Function (HRTF) datasets to denser HRTF datasets. However, depending on the number of sparse HRTF measurements and SH order, this process can introduce distortions in high frequency representation of the HRTFs. This paper investigates whether it is possible to restore some of the distorted high frequency HRTF components using machine learning algorithms. A combination of Convolutional Auto-Encoder (CAE) and Denoising Auto-Encoder (DAE) models is proposed to restore the high frequency distortion in SH interpolated HRTFs. Results are evaluated using both Perceptual Spectral Difference (PSD) and localisation prediction models, both of which demonstrate significant improvement after the restoration process.

We design an asymmetric nonlinear optical nanoantenna composed of a dielectric nanodisk and an adjacent nanobar. The proposed composite structure made of AlGaAs exhibits resonant response at both the fundamental and doubled frequencies. Being driven by the strong magnetic dipole resonance at the pump wavelength and a high-quality mode at the harmonic wavelength, the efficient second-harmonic radiation is generated predominantly along the vertical directions under the normally incident plane-wave excitation.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

The valley pseudospin properties of electrons in two–dimensional hexagonal materials result in lots of fascinating physical phenomena, which opens up the new field of valleytronics. The valley-contrasting physics aims at distinguishing the valley degree of freedom based on valley–dependent effects. Here, we theoretically demonstrate that both of the valley–selective high harmonic generation and valley–selective electronic excitation can be achieved by using an orthogonal two–color (OTC) laser field in gapped graphene. It is shown that the asymmetry degrees of harmonic yields in the plateaus, cutoff energies of generated harmonics and electron populations from two different valleys can be precisely controlled by the relative phase of the OTC laser field. Thus the selectivity of the dominant valley for the harmonic radiation and electronic polarization can be switched by adjusting the relative phase of the OTC laser field. Our work offers an all–optical route to produce the valley–resolved high harmonic emissions and manipulate the ultrafast valley polarization on a femtosecond timescale in condensed matter.

The growing demand for nutritious foods has spurred investigations into alternative sources of nutrition beyond traditional options. For this reason, the present study approaches the amaranth, which is a plant with high potential, highlighting the morphological growth, grain biomass pro-duction, and quantitative traits of seven varieties of amaranth cultivated in the pedoclimatic con-ditions of Somes meadow in Transylvania. A bifactorial trial was implemented with factors ama-ranth species and amaranth varieties. Two amaranth species and seven varieties were studied. Differences are reported between morpho-productive and quantitative traits of the seven amaranth varieties studied in this research. The interrelationships between amaranth morphological traits quantified by using Pearson simple correlations show that morphological traits moderately con-tribute to grain fresh biomass yield, while morphological traits and fresh biomass strongly con-tributed to grains dry biomass yield. Our study shows that morpho-productive, and nutritional characteristics of the seven amaranth varieties comprised by our study recommend the plans to be used in various nutritional aims, being a valuable replacer of traditional raw materials in specific food and feed industry sectors.

The authors propose a novel approach for a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while preserving animal life. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate-calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity, signs of neurological deficits (paresis, paralysis, etc.), as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.

The concept of neutrosophic number is a significant mathematical tool to deal with real scientific problems because it can tackle indeterminate and incomplete information which exists generally in real problems. In this article, we use neutrosophic numbers (a + bI), where a and bI denote determinate component and indeterminate component respectively. We explore the situations in which the input information is needed to express in terms of neutrosophic numbers. We define score functions and accuracy functions for ranking neutrosophic numbers. We then define a cosine function to determine unknown criteria weights. We define neutrosophic number harmonic mean operators and proved their basic properties. Then, we develop two novel MCGDM strategies using the proposed aggregation operators. We solve a numerical example to demonstrate the feasibility and effectiveness of the proposed two strategies. Sensitivity analysis with variation of “I” on neutrosophic numbers is performed to demonstrate how the preference ranking order of alternatives is sensitive to the change of “I”. The efficiency of the developed strategies is ascertained by comparing the obtained results from the proposed strategies with the existing strategies in the literature.

Mannosylerythritol lipids (MELs), one of the most promising biosurfactants (BS), are glycolipids produced by yeasts or fungi, with great environmental performance and a high compatibility with the human body. MELs besides working as typical surfactants, can form diverse structures when in the critical aggregation concentration (CAC), reducing the surface tension of water and other solutions, and being stable over a wide range of conditions. Among others, MELs present anti-microbial, antitumor, antioxidant and anti-inflammatory activity, skin and hair repair capacity, which opens possibilities for their use in applications from cosmetics and pharmaceutics to bio-remediation and agriculture. However, their market share is still low when compared to other glycolipids, due to their less developed production process and higher production cost. This re-view gathers information on the potential applications of MELs mentioned on the literature since 1993. Furthermore, it is also explored the current strategies being developed to enhance the market presence of MELs, in parallel with the ones developed for rhamnolipids and sophorolipids.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Several types of guided bone regeneration materials are available with various properties and clinical indications. Among them, dentin-derived matrix from extracted teeth is an excellent alternative to traditional graft materials, such as allografts and xenografts. Different clinical preparation protocols exist: block form versus powder form, demineralized versus non-demineralized form. Out of these methods, demineralization protocols for dentin-derived matrix from extracted teeth have been noted for a wide range of successful clinical outcomes. The purpose of this animal study was to find out the most effective method of demineralizing dentin-derived matrix to result in the highest regenerative ability in the bone graft material in rabbit calvaria. The study conducted a comparative histomorphometric analysis of four groups in distinguished matrix conditions: a control group without graft placement, a non-demineralized dentin-derived matrix graft placement group, a 15-minute demineralized dentin-derived matrix graft placement group, and a 30-minute demineralized dentin-derived matrix graft placement group. Regenerative processes were evaluated three times at 2, 4, and 8 weeks post-graft placement. These groups of rabbits were evaluated randomly in a blinded setting to prevent bias. Among the four groups compared, the group with a 15-minute demineralized dentin-derived matrix graft showed the most efficient bone regeneration in the histomorphometric analysis. Based on this animal study, it was apparent that a 15-minute demineralization of dentin-derived matrix is the preferred preparation protocol to maximize the regenerative potential in the matrix.

The bioactive marine sulfated polysaccharides ulvan and carrageenan, formulated in gels at 1.5, 5.0 and 10% w/w concentrations, were evaluated for their wound healing potential on second-degree burn wounds. The polysaccharide-based gels were administered on the burn-inflamed skin of hairless female SKH-hr2 mice, and the therapeutic effect of the various treatments was assessed based on histopathological analysis, the clinical condition of mice, photo-documentation, evaluation of biophysical skin parameters, and FT-IR spectroscopy.Clinical and histopathological assessment, as well as the reduction rate of the burn wound area, indicated that the 10% w/w carrageenan gel significantly enhanced wound healing, especially at the early stages of the healing process, recovering both the α-helix of collagen and the glycosaminoglycans configuration as evidenced by the FT-IR absorption bandsof skin in vivo and ex vivo. At later stages, the healing effect of the 5% w/w ulvan gel was also notably significant, indicating that carrageenan and ulvan wound dressing gels could potentially contribute to the efficient wound healing of burn wounds.

German noise action plans aim to reduce negative health outcomes from noise exposure and identify quiet areas free of noise pollution. Quiet area identification in German noise action plans is based primarily on noise mapping and spatial analysis and not empirical or qualitative data about acoustic environments, thus leaving a gap in the understanding of the quality of formally recognized quiet areas in noise action plans. This work presents a comparative empirical case study in Dortmund, Germany, with the aim to describe the diurnal dB(A) and biophonic properties of quiet areas versus noise 'hot spots'. Sound observations were collected (n=282,764) in five different natural or recreational land use patch types larger than four acres within 33 proposed quiet areas in Dortmund (n=70) and 23 noise hot spots between April 27^th, 2022 and March 2^nd, 2023. We find that quiet areas are on average more than 20 dB(A) quieter than noise hot spots almost every hour of the day. Forests, managed tree stands, cemeteries, and agriculture diel patterns are dominated by dawn dusk chorus in spring and summer, whereas sport and recreation as well as noise hot spots are dominated by traffic and human noise. A novel composite biophony mapping procedure is presented that finds distinct temporal distribution of biophony in forested and agriculture peri-urban locations positively associated with patch size, distance away from LDEN > 55, proximity to water, and the number of vegetation layers in the plant community. Anthrophony distribution dominates urban land uses in all hours of the day, but expands during day and evening and contracts at night and in dusk hours. The procedures presented here illustrate how qualitative information regarding quiet areas can be integrated into German noise action planning.

The interaction between the grid network and the offshore wind power plant (WPP) network can lead to the amplification of certain harmonics and potentially resonant conditions. Offshore WPP should limit the increment of harmonic voltage distortion at the point of connection to the grid network as well as within their internal network. The harmonic distortion should be limited within the planning level limits using harmonic compensation, which is usually achieved by using static filters. In this paper an active damping compensation strategy with a STATCOM using emulation of resistance at the harmonic frequencies of concern is analysed. Such a compensation is effective for the local bus, though the performance is not guaranteed at the remote bus. This paper investigates the challenges associated with remote harmonic compensation in the offshore WPP, which is connected to the onshore grid through long high-voltage cables and transformers. First, the harmonic distortion and the compensating effects of the filter are theoretically assessed. Afterwards, they are demonstrated using harmonic propagation studies and time domain simulations in PSCAD.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

Background: The aim of this experimental work was to evaluate cheiloscopy potential: to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject, with a focus on assessing the method's limitations. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants. All the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, but the absence of a database greatly limits its use. Additionally, its use for sex identification does not seem to be reliable. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

We report on the application of femtosecond laser micromachining to the fabrication of complex glass microdevices, for high-order harmonic generation in gas. The three-dimensional capabilities and extreme flexibility of femtosecond laser micromachining allow us to achieve accurate control of gas density inside the micrometer interaction channel. This device gives a considerable increase in harmonics generation efficiency if compared with traditional harmonic generation in gas jets. We propose different chip geometries that allow to control the gas density and driving field intensity inside the interaction channel to achieve quasi-phase matching conditions in the harmonic generation process. We believe that these glass micro-devices will pave the way to future downscaling of High-order Harmonic Generation beamlines.

Hematological malignancies refer to a heterogeneous group of neoplastic conditions of lymphoid and hematopoietic tissues classified in leukemias, Hodgkin and non-Hodgkin lymphomas and multiple myeloma, according to their presumed cell of origin, genetic abnormalities, and clinical features. Metabolic adaptation and immune escape, which influence various cellular functions including proliferation and survival of hematological malignant tumor cells, are major aspects of these malignancies that lead to therapeutic drug resistance. Targeting specific metabolic pathways is emerging as novel therapeutic strategy in hematopoietic neoplasms, particularly in acute myeloid leukemia and multiple myeloma. In this context, CD147, also known as Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) or Basigin, is one target-candidate involved in reprogramming metabolism in different cancer cells, including hematological malignant tumor cells. CD147 overexpression significantly contributes to the metabolic transformation of these cancer cells, by mediating signaling pathway, growth, metastasis and metabolic reprogramming, through its interaction, direct or not, with various membrane proteins related to metabolic, regulation including monocarboxylated transporters, integrins, P-glycoprotein and Glucose Transporter 1. This review explores the metabolic functions of CD147 and its impact on the tumor microenvironment, influencing the progression and neoplastic transformation in leukemias, myeloma and lymphomas. Furthermore, we highlight new opportunities for the development of targeted therapies against CD147, potentially improving the treatment of hematologic malignancies.

Deep Eutectic Solvents (DESs) show promising abilities for the delamination of multilayer packaging films that are used in food packaging and in pharmaceutical blister packs. Due to the complexity of their structure, the recycling of these materials is a challenging task, leading to the easiest or cheapest option, landfilling. Towards the development of ‘green’ solvents for the efficient waste management and recycling, the conducted research focuses on the preparation of a range of hydrophobic and hydrophilic DES based on carboxylic acids. Also, their chemical and physical characterization, such as DSC, rheometer and density measurements, was followed for the determination of their properties. The laminate packaging waste products that were tested were Al/PE, PE/Al/PET, Al/PE/paper and PVC/PE/Al. Different batches of solvent systems were tested based on various naturally derived aliphatic and aromatic organic compounds as well as amino acids. The separated films were collected and studied further for the examination of the delamination extend. Results showed full or partial delamination of some materials as well as challenges of solvent systems. Variables such as temperature, agitation rate, mixing time and solvents ratios were monitored and collected during the design of experimental process. The results showed that the used DESs can offer an efficient, low-energy, affordable and green option for the delamination tested packaging materials.

In this study, we analyzed the microbial community of traditional fermented foods in Jeju Island to identify the distribution of useful microorganisms and confirm their anti-inflammatory and anti-melanogenic effects to determine their potential use as cosmetic ingredients. Firstly, we examined the microbial communities of Omphalius rusticus Jeotgal (OR), Spratelloides gracilis Jeotgal (SG), Chromis notata Jeotgal (CN), Turbo cornutus Jeotgal (TC), Trichiurus lepturus intestine Jeotgal (TL), Branchiostegus japonicus Sweet Rice Punch (BJ), Salted Anchovy Sauce (SA), Jeju Soy Sauce (JSS), and Jeju Soybean Paste (JSP). We found that Latilactobacillus sakei (87.2%), Tetragenococcus halophilus (37.7%), T. halophilus (96.8%), Bacillus subtilis (23.4%), T. halophilus (71.3%), L. sakei (53.7%), Lentibacillus sp. (42.9%), Enterococcus durans (14.6%), and E. durans (32.8%) were the dominant species. Secondly, to study the nine Jeju fermented foods’ anti-inflammatory and anti-melanogenic effects, we employed RAW 264.7 and B16F10 cells, classic cell models for inflammation and melanogenesis studies. Ethyl acetate extracts of the nine Jeju fermented foods all inhibited nitric oxide (NO) and melanin production in a concentration-dependent manner. Thirdly, to test the applicability of the nine Jeju fermented foods to human skin, we used the MTT assay to assess their cytotoxic effects on human keratinocytes (HaCaT cells). Finally, the topical applicability of the nine Jeju fermented foods was tested through primary skin irritation, and it was found that they did not cause any adverse effects. Therefore, extracts from the nine Jeju fermented foods have potential applications as ingredients in anti-inflammatory and anti-melanogenic products and can be used in the cosmetic industry.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), facilitation of short-chain fatty acids (SCFAs) production, activation of the glucagon-like peptide 1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we have discussed research in other disease models that use probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

This paper presents an improved droop control strategy for grid-connected inverter power stability and power quality under distorted with consideration of grid fluctuation and inter-harmonics. An instantaneous frequency without PLL and amplitude of capacitor voltage feed-forward control strategy is given to power stability control, meanwhile a grid current feedback control is given by an incomplete derivation with a high-pass filter, so that the harmonics and inter-harmonics current can be suppressed. These approaches can provide both good active and reactive power dynamic response under fluctuation of frequency, and rejection ability against harmonic and inter-harmonic voltage. Based on model of inverter, the proposed control strategies are designed in detail. Simulations and experiments are present to validate the effectiveness of proposed method.

Spodoptera frugiperda (J.E. Smith) is a global agricultural pest that poses a threat to crop production, characterized by its refractory polyphagous nature that makes it difficult to control and may lead to damage to woody plants. However, research on its adaptability to woody plants remains limited. This study compares the feeding adaptations (survival rate, pupation time, pupation rate, weight, length, and feeding volume), protective enzyme activities, and feeding preferences of S. frugiperda on leaves of six economically significant tree species (Areca catechu, Aquilaria sinensis, Cocos nucifera, Camellia oleifera, Dalbergia odorifera and Hevea brasiliensis) and maize as a control treatment. The results indicate that A. sinensis as the most vulnerable trees in high risk, H. brasiliensis and C. nucifera presented varying degrees of susceptibility, A. catechu, C. oleifera, and D. odorifera were unsuitability for S. frugiperda. In conclusion, this report extensively explores the feeding effects of S. frugiperda on six economically important tree species, and provides insights into the feeding preferences on these plants, thereby informing the potential threat posed by S. frugiperda to economically vital trees.

DC-connected parallel inverter systems are gaining popularity in industrial applications. However, such parallel systems generate excess current ripple (harmonics) at the DC-link due to harmonic interactions between the inverters in addition to the harmonics from the PWM switching. These DC-link harmonics cause the failure of fragile components such as DC-link capacitors. This paper proposes an interleaving scheme to minimize the current harmonics induced in the DC-link of such a system. The results show that when the carrier waves of the two inverters are phase-shifted by 90° angle, the maximum high-frequency harmonic ripple cancellation occurs, which reduces the overall RMS value of the DC-capacitor current.The outcome of this proposed solution is a cost-effective DC-harmonics mitigating strategy for the industrial designers to practically configuring multi-inverter systems, even when most of the drives are not operating at rated power levels. Experimental and simulation results presented in this paper verify the effectiveness of the proposed carrier-based phase-shifting scheme for two different configurations of common DC connected multi-converter systems.

Background: Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcome, which opens up new avenues for using them in personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in preoperative diagnosis of aggressive variants of papillary thyroid cancer. Methods: The molecular genetic profile (expression levels of 34 different markers and BRAF mutation) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Results: Statistically significant differences with adjustment for multiple comparisons (p &lt; 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, FN1, and CDKN2A. Weak statistical correlation (0.0015&lt; р&lt;0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. Conclusions: The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, the fibronectin and cyclin-dependent kinase inhibitor 2A genes.

Aim: The aim of this study is to evaluate the possibility of discriminating between the two sexes through the simultaneous use of cheiloscopy and palatine rugoscopy. Materials and methods: 80 palate and lip impressions (40 male and 40 female) were analyzed. The palate impressions were acquired using both analogue and digital methods. The lip impres-sions were first acquired analogically and then scanned. The morphology of the palatine rugae in the palate impressions was analyzed, with the exclusion of segmental rugae. The lip prints were analyzed in sextants and the morphology of the lip wrinkles was evaluated. Results: Palatine rugoscopy shows that women have more curvy rugae than men and that men have more rugae on the left side than on the right. Cheiloscopy gave no statistically significant re-sults. Discussion: Palatine rugoscopy showed some differences between the sexes, however, these re-sults were not solid enough for reliable sex discrimination. Differences between the results of dif-ferent studies can be attributed to ethnic and methodological variations. Cheiloscopy, on the other hand, did not provide statistically significant results for sex discrimination. Conclusions: Given the scant results obtained from palatine rugoscopy and the lack of statisti-cally relevant results in cheiloscopy, together with a lack of concordance among the data found in literature, it is believed that it is not possible to discriminate between the two sexes by using the two methods contemporarily. Further research is needed.

Long COVID, also referred to as post-COVID-19 condition, describes the lingering after-effects of COVID-19 infection. This complex syndrome encompasses a range of symptoms affecting physical well-being, cognitive function, and mental health. The widespread impact of long COVID extends beyond individual sufferers, placing significant strain on healthcare systems and causing far-reaching socioeconomic consequences. The scale of this multifaceted health crisis is unparalleled in recent history, affecting millions globally and challenging our understanding of post-viral conditions. This study aimed to explore the possibility of targeting G protein-coupled receptors (GPCRs) signaling pathway-related genes as therapeutics for long COVID using computational analysis. Targeting GPCRs and their signaling pathways holds significant promise for long COVID therapeutics, as these receptors are involved in crucial physiological processes including immune regulation, inflammation control, and neurotransmission. All of these are implicated in the diverse and persistent symptoms of long COVID, potentially offering a versatile approach to addressing multiple aspects of the condition simultaneously. This study identified 21 genes associated with GPCRs for further exploration as potential targets. Notably, GPCR genes such as HRAS, KRAS, GNAQ, and GNA11 were determined to be possible therapeutic targets for the pathophysiological mechanisms of long COVID. FDA-approved drugs targeting these genes were identified, including Binimetinib, Cabozantinib, Selumetinib, Panitumumab, Cetuximab, Adagrasib, Tipifarnib, and Sotorasib. Additionally, Naltrexone and Tipifarnib have emerged as potential new treatment options for long COVID. SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport, contributing to the pathophysiology of pulmonary edema in patients with COVID-19. Further research is required to translate the findings into the development of therapeutics and to investigate the relationship between viral infection and GPCR signalling.

The crystal structure of a polymorph of Glycyl-L-alanine HI.H2O was synthesized from chiral cyclic Glycyl-L-alanine dipeptide, known to show molecular flexibility in different environments. The space group is polar (P21) and therefore pyroelectricity and optical second harmonic generation properties are allowed by symmetry. We report a pyroelectric coefficient as high as 45 µC/m2K occurring at 345 K, one order of magnitude smaller than the semi-organic ferroelectric Triglycine Sulphate (TGS) crystal. Furthermore, the polymorph displays a nonlinear optical effective coefficient of 0.14 pm/V, around 14 times smaller than the value from a phase-matched inorganic Barium Borate (BBO) single crystal.

Antibiotic resistance is a global health problem. The human gut microbiome is implicated in the dynamics of antibiotic resistance acquisition and transmission, with the gut microbiota thought to play a crucial role. This study aimed to determine the potential influence of human gut bacteria microbiota on the gut resistome and the relationship between gut background microbiota and Escherichia coli resistome. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was used to systematically review studies that characterised gut microbiota and resistome using metagenomic analysis and/or those that reported gut E. coli resistome in healthy individuals. Changes in the diversity and abundance of bacterial gut microbiota and the resistome across different groups and the microbiota composition of the gut harbouring antibiotic-resistant E. coli were summarised. Findings suggest that lower bacterial microbiota diversity is likely associated with an increased abundance of the overall gut resistome. Age-related differences were observed, with younger infants exhibiting lower microbiota diversity and higher ARG abundance compared to older infants and adults. Studies that reported correlation revealed positive correlations between the compositional relative abundance of Proteobacteria and ARGs abundance, mainly driven by members within the Enterobacteriaceae family, particularly E. coli. This study also revealed that human gut microbiome studies that investigate gut resistome using metagenomic sequencing approaches in apparently healthy individuals are at least uncommon.

Mitochondria play a significant role in the functioning of the cell, acting both as an intracellular energy source and a signaling organelle. In the heart, mitochondria produce more than 95% of the ATP in addition to regulating the redox state, calcium homeostasis, apoptosis, and lipid synthesis. However, there is also evidence that mitochondria exist outside of cells where they have been observed to mediate cell-to-cell communication, repair, and participate in the immune response. Cardiometabolic disease (CMD) has a complex pathogenesis closely associated with mitochondrial dysregulation, inflammation, and metabolic abnormalities. Because of this metabolic interdependence between the myocardium and the intracellular mitochondria, circulating extracellular mitochondria (CEMI) are being identified as possible regulators of CMD. Outside of the cell, mitochondrial functions are determined by the mitochondrial form, either as whole functional structures (e.g., small extracellular mitochondria) or as mitochondrial components with or without membrane encapsulation. Here, we explore the different forms of CEMI, their role in CMD pathogenesis, their potential therapeutic utility in treating diseases, and their role as biomarkers.

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

We discuss a central concept of nanothermdynamics; the subdivision potential. We explain how it can be measured or calculated for some typical ensembles, as this has been disputed in the literature. We proceed to discuss its meaning for particular systems, and predict scaling laws for three ensembles. The laws depend on the small system geometry in a predictable way for an ideal gas model with surface adsorption. We provide new equations which relate the subdivision potential to experimental investigations, and give expressions for grand canonical ensembles of spheres, cylinders, slit pores and fluids confined in porous media. The subdivision potential is not compatible with the popular Hadwiger theorem in geometry, and can therefore not be described by a Minkowski set of variables. It is equivalent to Gibbs descriptions when shape- and size variables are defined.

New furan, thiophene and triazole oximes were synthesized through several-step reaction paths to investigate their potential for development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Acute OP poisoning is still a challenge in treating patients despite the development of a large number of oxime compounds that should have the capacity to reactivate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The activity of these two enzymes, crucial for neurotransmission, are blocked by the OP, which has the consequence of disturbing normal cholinergic nerve signal transduction in the peripheral and CNS, leading to cholinergic crisis. Oximes in use have one or two pyridinium rings and cross the brain–blood barrier poorly due to the quaternary nitrogen. Following our recent study on 2-thienostilbene oximes, in this paper we described the synthesis of 63 heterostilbene derivatives out of which 26 oximes were tested as inhibitors and reactivators of AChE and BChE inhibited by OP nerve agents – sarin and cyclosarin. While the majority of oximes were potent inhibitors of both enzymes in micromolar range, we identified several oximes as BChE or AChE selective inhibitors with a potential for drug development. Moreover, even oximes were poor reactivators of AChE, four heterocyclic derivatives reactivated the cyclosarin-inhibited BChE up to 70%, and cis,trans-5 [2-((Z)-2-(5-((E)-(hydroxyimino)methyl)thiophen-2-yl)vinyl)benzonitrile] had comparable reactivation efficacy to the standard oxime HI-6. In silico analysis and molecular docking studies connected the kinetic data to the structural features of these oximes, and confirmed their productive interactions with the active site of the cyclosarin-inhibited BChE. Based on inhibition and reactivation and their ADMET properties regarding lipophilicity, CNS activity, and hepatotoxicity, these compounds could be considered for further development of CNS-active reactivators in OP poisoning as well as cholinesterase-targeted therapeutics in neurodegenerative diseases like Alzheimer’s and Parkinson’s.

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process disrupted in preeclampsia, characterized by elevated vascular resistance, re-duced utero-placental blood flow and intrauterine growth restriction. This study investigated PP13’s role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries isolated from both pregnant and non-pregnant women were precontracted with the thromboxane analogue U46619, and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated using specific inhibitors for ni-tric oxide synthase (L-NAME+LNNA at 10-4 M) and guanylate cyclase (ODQ at 10-5 M). Results showed PP13 induced vasodilation in uterine arteries but not in subcutaneous arteries. Ad-ditionally, PP13 counteract U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13's mechanism of action is dependent on activa-tion of the Nitric oxide-cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine ar-teries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest PP13 may be a promising candidate for improving utero-placental blood flow in condi-tions such as preeclampsia. Further research and clinical studies are warranted to validate PP13's efficacy and safety as a therapeutic agent for managing preeclampsia.

We introduce a series of twisted donor-acceptor (D-A) carbazole-benzophenone based electroactive bipolar derivatives that were synthesized through the reaction of 4-fluorobenzophenone with various partially alkylated 3,3’-bicarbazoles. The comprehensive structural characterization of these compounds is provided. These amorphous materials exhibit suitable glass transition temperatures ranging from 57 to 102 °C and demonstrate high thermal stability, with decomposition temperatures reaching 400 °C. Moreover, the developed materials exhibit elevated photoluminescence quantum yields (PLQY) of up to 75.5% and favorable HOMO-LUMO levels, along with suitable triplet-singlet state energy values. Due to their good solubility and suitable film-forming properties, all the compounds were evaluated as blue emitters dispersed in 4,4’-bis(N-carbazolyl)-1,10-biphenyl (CBP) host for the fabrication of organic light-emitting diodes (OLEDs) in concentration dependent experiments. Among these experiments, the device containing 15 wt% of the guest 4-(9’-{2-ethylhexyl}-[3,3’]-bicarbazol-9-yl)benzophenone demonstrated the best characteristics, achieving maximum brightness of 3581 cd/m2, current efficiency of 5.7 cd/A, power efficiency of 4.1 lm/W and external quantum efficiency of 2.7%.

Cell-culture meat is a novel concept to replace traditional meat produced from animals, and to satisfy rising food demands due to the world population growth. It is still a young field and requires to solve technical issues including cell sources and types, efficient culture for large scale production, taste and texture for customer satisfaction. The current review summarized traditional beef meat production and evaluation methods for customer satisfaction. In particular, serum biomarkers for beef meat evaluation are discussed, which can be applicated for cell-culture meat production.

Long COVID, characterized by persistent symptoms lasting from weeks to several months following initial infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), significantly impacts individuals' quality of life and poses a potential long-term burden on global healthcare systems. Clinical manifestations of Long COVID are diverse, affecting multiple systems including respiratory, cardiovascular, neurological, and gastrointestinal. While the precise mechanisms underlying Long COVID remain unclear, emerging evidence suggests involvement of various bodily pathways. This study employs bioinformatics tools to investigate the mechanisms of Long COVID and identify potential drug targets associated with key pathways, including inflammation, cytokines, immune response, coagulation, mitochondrial function, oxidative stress, and autonomic dysfunction. Tools such as the National Center for Biotechnology Information (NCBI) database, PubChem, UniProt, and iGEMDOCK were utilized for pathway analysis and molecular docking. The analysis aimed to identify drug molecules that may interact with target proteins to regulate or inhibit pathway activity, yielding several potential drug candidates for further investigation.

With a predominantly humid tropical climate and a large area for expanding agricultural activities, Angola has in principle favorable conditions for bioenergy production. The focus of this study was to evaluate the availability of suitable land for producing sugarcane. This crop is highly efficient in converting solar energy into biomass for energy purposes in Angola. To this end, the Global Agro-Ecological Zones database, GAEZ v4, developed by IIASA and FAO, with the aid of the QGIS version 3.22.5, has been used to identify areas suitable for sugarcane cultivation, considering four levels of suitability. Aiming at the sustainability of bioenergy production, areas dedicated to food production, protected areas, and areas with slopes above 16% were excluded. Under these criteria, this study identified the existence of 6.3 Mha in lands of good agricultural suitability, with water resources, corresponding to 5% of the Angolan territory, distributed in seven provinces of the country, especially in the provinces of Cuando Cubango and Cunene, where 85% of the very suitable land under irrigation is located. Adopting a model of agricultural productivity, assuming irrigation and adequate agricultural practices, such area could produce approximately 956 million ton of sugarcane annually, which is significantly higher than the current production in this country, This amount of feedstock, processed using current technology could potentially produce 81.3 GL of ethanol and 176,9 TWh of electricity with low GHG emission per year, able to mitigate, as a whole, circa 60.3 MtCO2-eq/year by displacing gasoline in light vehicles and diesel and natural gas consumed in power generation.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

The potential use of nanostructured dipeptide self-assemblies in materials science for energy harvesting devices is a highly sought-after area of research. Specifically, aromatic cyclo-dipeptides containing tryptophan have garnered attention due to their wide-bandgap semiconductor properties, high mechanical rigidity, photoluminescence, and nonlinear optical behavior. In this study, we present the development of a hybrid system comprising biopolymer electrospun fibers incorporated with the chiral cyclo-dipeptide L-Tryptophan-L-Tyrosine. The resulting nanofibers are wide-bandgap semiconductors (bandgap energy 4.0 eV) and consist of self-assembled nanotubes embedded within a polymer matrix, exhibiting intense blue photoluminescence. Moreover, the cyclo-dipeptide L-Tryptophan-L-Tyrosine incorporated into polycaprolactone nanofibers displays a strong effective second harmonic generation signal of 0.36 pm/V and also shows notable piezoelectric properties with a high effective coefficient of 22 pCN−1. These hybrid systems hold great promise for applications in the field of nanoenergy harvesting and nanophotonics.

Neuropathic pain (NeP) is a complex and debilitating condition that impacts millions of people globally. Although various treatment options exist, their effectiveness is often limited, and they can be accompanied by significant side effects. In recent years, there has been increasing interest in targeting the N-methyl-D-aspartate receptor (NMDAR) as a potential therapeutic approach to alleviate different types of neuropathic pain. This narrative review aims to provide a comprehensive examination of NMDAR antagonists, specifically ketamine, memantine, methadone, amantadine, carbamazepine, valproic acid, phenytoin, dextromethorphan, riluzole, and levorphanol, in the management of NeP. By analyzing and summarizing current preclinical and clinical studies, this review seeks to evaluate the efficacy of these pharmacologic agents in providing adequate relief for NeP.

Global warming may increase the potential evapotranspiration (Etp), thereby affecting the amount of clean water resources available in a region. In this study, the systematic biases in temperature outputs of 24 global climate models (GCMs) under 3 emission scenarios are corrected by using 8 bias correction methods. The trend of Etp in Yangzi River Delta in the 21st century is projected by using 4 Etp calculation formulas. The uncertainty of the projections is estimated and decomposed by using multi-way analysis of variance. The influence of uncertainty on the projected change signal is quantified by using the signal-to-noise ratio. The results show that, relative to the reference period (1971~2000), the annual mean daily Etp in Yangzi River Delta will increase by 0.14~0.17mm/d during the period 2021~2050 and by 0.21~0.41mm/d during the period 2061~2090, respectively. During 2021~2050, the uncertainty of Etp increase projections is dominantly contributed by the main effects of GCM (63%) and Etp calculation formula (24%). During 2061~2090, it is mainly contributed by the main effect of GCM (36%), followed by the main effects of emission scenario (34%) and Etp calculation formula (18%). The increase projections of Etp are generally reliable and robust during the two projection periods.

In this paper, the stabilization and high efficiency of an unstable Second Harmonic Generation (SHG) of a Nd : YVO4 laser with a KTP intracavity is carried out by using a passive Q-switching crystal and a parametric modulation method (harmonic modulation) is shown. The harmonic modulation was defined as um(t) = Amsin(2π fmt), with modulation amplitude as Am(Vpp), and modulation frequency as fm(Hz), applied to the pumping of the Nd : YVO4 -KTP laser to control the amplitude and frequency of the emission, thus stabilizing the dynamic states of this laser. The promising application of this green light source is materialized when such light is necessary for high-density optics, such as in the treatment materials industry or in some aesthetic applications.

The rapid growth of the sharing economy has propelled shared mobility to the forefront of attention. The continuous advancement of autonomous driving technology also brings new opportunities and challenges to the shared mobility market. This study comprehensively analyzes the market potential concerning autonomous vehicles (AVs) to provide shared mobility services, utilizing SWOT analysis, PESTLE analysis, and Porter’s Five Forces. The findings reveal that AVs can provide improved shared mobility services by increasing transportation safety, reducing emissions, reducing costs, enhancing traffic efficiency, and increasing customer satisfaction and the profitability of shared mobility services. However, challenges such as technological and policy uncertainties, safety concerns, high initial costs, inadequate public communication infrastructure, and the absence of standardized regulations can hinder the widespread adoption of AVs. The benefits are also restricted with a low market penetration rate of AVs. To promote AVs in the shared mobility market, this study also provides implications for AV stakeholders tailored to the evolving shared mobility market dynamics.

Identifying locations of landslide slip surfaces provides critical information for understanding the volume of landslides and the scale of disasters, which is essential for formulating disaster preparedness and mitigation strategies. Based on hydrogeological survey data from 24 deep-seated landslide-prone sites in Taiwan's mountainous regions, this study first developed the hydraulic conductivity potential index (HCPI) using principal component analysis to quantify hydraulic properties of disturbed rock formation with six geological factors. Then, The regression analysis was performed to construct a permeability estimation model for the geological environment of landslides. Finally, the established model was utilized to develop an identification method for potential slip depths in landslide-prone sites. Results indicated a strong relation between HCPI and hydraulic conductivity with a determination coefficient of 0.895. The relation equation confirmed that its generated data concerning the depths of significant changes in hydraulic conductivity could be used to identify potential slip surfaces. Additionally, this study successfully establishes a rule for identifying potential slip zones by summarizing data concerning the generated hydraulic conductivity profiles, stratigraphic lithology, existing inclinometer slip depth records, and groundwater level of landslide sites. This identification method was then applied to predict potential slip depths for ten landslide sites where slip surfaces have not yet occurred. These findings offer a new alternative to having early information on potential sliding depths for timely disaster management and control implementation.

During the last years there has been a high interest in the development of new purely-organic single-component conductors. Very recently, we have reported a new neutral radical conductor based on the perchlorotriphenylmethyl (PTM) radical moiety linked to a monopyrrolo-tetrathiafulvalene (MPTTF) unit by a -conjugated bridge (1). Interestingly, this system behaves as a semiconductor with high conductivity and small energy gap under high pressure. With the aim of developing a new material with improved conducting properties, we have designed and synthesized the radical dyad 2 which was functionalized with an ethylenedithio (EDT) group in order to improve the intermolecular interactions of the TTF subunits. The physical properties of the new radical dyad 2 were studied in detail in solution to further analyze its electronic structure as well as its potential use as radical conductor in the solid state.

The optimal regime of three-photon resonant excitation of a helium atom by a femtosecond ul-traviolet (UV) pulse was discovered and numerically studied, at which the maximum power of the third harmonic of the UV field is achieved in the spectrum of dipole acceleration (the second time derivative of the induced dipole moment) of the atom. It is shown that the optimal frequency of the UV field nearly coincides with the frequency of the three-photon transition 1s2 – 1s2p, taking into account its shift as a result of the dynamic Stark effect, and the intensity of the UV field is dictated by the condition of maximizing the product of the populations of the 1s2 and 1s2p states, averaged over the time interval during which the UV field is non-zero. For the considered UV field durations, from 10 to 100 cycles of the carrier frequency (from units to tens of femtoseconds), the optimal intensity lies in the range from 10^14 W/cm^2 to several units of 10^14 W/cm^2. It is shown that with an optimal choice of the frequency and intensity of the UV field, the dynamics of excitation of bound and continuum states, as well as the shape of the time envelope of the dipole acceleration of the atom, weakly depend on the duration of the UV field envelope; only their time scale changes significantly. In addition, under the optimal conditions the average power of the third harmonic signal in the dipole acceleration spectrum is practically independent of the duration of the UV field envelope.

Buttonweed (Cotula coronopifolia) is native to South Africa but invasive in wetlands in Europe, North America, and Australasia, where it excludes native plants. Despite being dry-fruited, field studies suggest migratory waterbirds can disperse its seeds via gut passage (endozoochory), aiding its expansion. To explore the potential for endozoochory in different regions and habitats, we collected seeds from six populations in Spain, Sweden, and the UK. Germination was tested under different salinity levels (0, 5, 10, 15 g/L) and simulated gut passage treatments: scarification, acidification, or both. No germination occurred at 15 g/L. Higher salinity reduced and delayed germination, but full gut passage treatment increased germinability and accelerated germination. Scarification or acid treatment alone resulted in intermediate germination patterns. There were significant salinity x population and gut passage x population interactions on germinability. The acceleration effect of gut passage on germination was stronger at 5-10 g/L than at 0 g/L. This study highlights how migratory birds can facilitate the spread of alien plants introduced by humans. Non-classical endozoochory by waterbirds is an understudied mechanism for the long-distance dispersal of dry-fruited alien plants. Further research on C. coronopifolia, including population genetics, is necessary to understand dispersal mechanisms and facilitate management strategies.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

The capability of large food retail chains to respond quickly to changes in consumer behaviour and their dominant market position affects all food market players and often conflicts with the interests of national food producers, which can reduce the presence of locally sourced products in the food product mix in the country. In Latvia, there have been several proposals to limit retailers' opening hours on weekends and public holidays to increase the viability of small local food producers, retailers, and catering enterprises; however, limiting retailers' opening hours without research-based arguments is unacceptable. The research studies conducted in Europe also do not give a unified conclusion. Household consumer behaviour in the food market is viewed as an essential argument for increasing domestic demand and economic stability. Accordingly, the present research aims to identify the impacts of diversification of opening hours of food supermarkets on consumer shopping habits and the implications for creating an advantage for small and medium agri-food producers in selling their products. The research applied a quantitative approach to identify the main trends in society (n=2738), with a survey including 31 variables to quantify consumer behaviour, values, and opinions and seven socio-demographic variables. If a decision were made in Latvia to close grocery shops on Sundays or reduce their opening hours on weekends, 85% of consumers indicated that they would be unlikely to change their usual shopping location and would plan to shop at a supermarket on other days. The choice between farmers' markets and local food shops on Sundays would be made by 45% of consumers, with more than half (53%) of them shopping at local food shops at least a few times a month. It could, therefore, be argued that reducing the opening hours of supermarkets and closing them on Sundays and public holidays do not provide a competitive advantage and do not divert consumers to small and medium agri-food producers.

The composition simplex (N, P, K, Ca, and Mg) of the leaf is the main scores used by different approaches like the Diagnosis and Recommendation Integrated System and Compositional Nutrient Diagnosis to study the nutrient interactions and balance in plant leaves. However, the application and validation of these concepts to grain composition remains unexplored. Contrary to foliar analysis's early intervention for nutrient deficiency detection and correction, applying this approach to seeds assesses diverse cultivars' potential, enabling anticipation of their adaptation to climate conditions and informed selection for future crops. In the present study, a collected database of more than 924 scores including the grain yield (kg ha-1) and the nutrient composition (mg kg-1) of different corn varieties is used to develop a novel nutrient-based diagnostic approach to identify reliable markers of nutrient imbalance. A 'nutrient signature' model is proposed based on the impact of the environ-mental conditions on the nutrient indices and composition (N, P, K, Ca, and Mg) of the corn grains. The yield threshold used to differentiate between low and high-yielding subpopulations is established at 12.000 kg ha-1and the global nutrient imbalance index (GNII) of 2.2 is determined using the chi-square distribution function and vali-dated by the Cate-Nelson partitioning method, which correlated yield data distribution with the GNII. Therefore, the nutrient compositions were classified into highly balanced (GNII ≤ 1.6), balanced (1.6 < GNII ≤ 2.2), and imbalanced (GNII > 2.2). In addition, we found that the Xgboost model's predictive accuracy for GNII is signif-icantly affected by soil pH, organic matter, and rainfall. These results pave the way for adapted agricultural practices by providing insights into the nutrient dynamics of corn grains under varying environmental conditions.

Lyme disease is a highly prevalent tick-borne infection caused by Borrelia burgdorferi spirochetes in North America and Eurasia. Diagnosis of the early disease remains difficult with the currently approved serological tests in the absence of noticeable tick bite or erythema migrans due to presentation of non-specific symptoms and the absence of antibodies early in infection. Furthermore, it is difficult to distinguish persistence of disease and reinfection in the endemic regions. If not treated early, infection spreads throughout the body and affects most organs with disease manifestations including arthritis, musculoskeletal pain, neuroborreliosis and acrodermatitis chronicum atrophicans. Although most patients recover after antibiotic treatment, ~10-12% of show recurrence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). Various causes of PTLDS are not well-defined; however, the spirochete persisters, antigenic debris, dysregulation of immunological response in individuals or a combination of these factors are proposed to result in continuation of Lyme disease manifestations. Based on these considerations, this review highlights currently employed treatment approaches with antimicrobials and vaccines being tried for prevention of B. burgdorferi infection. We also summarize combinatorial approaches that could be employed to alleviate symptoms to improve the quality of life of the individuals suffering from long Lyme disease.

The valorization of aquaculture/fisheries processing by-products, as well as unavoidable/unwanted catches and discards in Greece is currently an underutilized activity despite the fact that there are several best practices in Northern Europe and overseas. One of the main challenges is to determine whether the available quantities for processing are sufficient to warrant valorization of discards and fish side streams. This is the first attempt to systematically record and analyze the available quantities of fish by-products and discards in Greece in a spatial and temporal way in an effort to create a national exploitation Master Plan for the valorization of this unavoidable and unwanted biomass. A thorough survey conducted within the VIOAXIOPIO project unveiled a substantial biomass of around 19,000 tonnes annually that could be harnessed for valorization. Furthermore, the production of various High Added Value Biomolecules (HAVB) was investigated, and experimental trials were conducted to assess the potential yields and the collected data were used to formulate four valorization scenarios.

Age-related brain deterioration and Alzheimer's disease (AD) pose major challenges as misfolded proteins are deposited in the brain, leading to a decline in cognitive abilities and disruption of neural networks crucial for memory. This article addresses the impact of disrupted spike-timing-dependent plasticity (STDP) mechanisms in Alzheimer's disease and highlights the role of Transcranial magnetic stimulation (TMS) in the study of cortico-cortical spike-timing-dependent plasticity. Amidst this adversity, the role of STDP emerges as a key player in memory formation by synchronizing neural activity. Progressive neuronal dysfunction decreases neural plasticity and impairs manual dexterity and speed, echoing more general problems in elderly people. The findings highlight the potential of neurally-driven cortico-cortical paired associative stimulation (ccPAS) to revitalize neural plasticity and improve motor performance in elderly people, bridging the gap between age-related challenges and Alzheimer's research. This work opens a door to potential rehabilitation strategies for aging populations by unlocking the aging brain's ability to improve motor performance.

A burgeoning body of scholarship identifies and discusses botanic gardens as increasingly important centres of biodiversity conservation and sustainability. Notwithstanding the high quality and richness of this literature, it encompasses relatively autonomous fields of expertise that are neither designed nor expected to promote cross-disciplinary, integrative, accounts of botanic gardens as institutions of conservation and sustainability. Bridging key aspects of the botanic garden literature, this article brings into conversation historical accounts with contemporary scholarship on the matter. In so doing, it unveils dilemmas and challenges faced by botanic gardens as they grapple with their historic legacies, but also renew their relevance in nurturing sustainable socio-environmental futures. The article proceeds by covering three focal points. First, it summarizes the scholarly literature on the history of botanic gardens. Second, it presents accounts of current scientific and biodiversity conservation endeavours as reflexive engagements with their historical legacies. Third, it addresses the recent emergence of socio-cultural missions at botanic gardens as a significant step beyond their historical focus on plants and plant ecosystems.

Systemic Lupus Erythematosus (lupus) and B-cell lymphoma (lymphoma) are serious diseases. Lupus and lymphoma co-occur at higher-than-expected rates and primarily depend on B-cells for their pathology, implicating shared inflammation-related B-cell molecular mechanisms as a potential cause of co-occurrence. We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B-cell RNA-seq data to find shared- and contrasting mechanisms potentially targetable for treatment. We observed 8,562 genes significantly dysregulated in both lupus and lymphoma. Of those genes, we found 5,335 to have a significant immune imbalance, defined as significant dysregulation by both diseases, as determined by IIT. Gene Ontology (GO) term and pathway enrichment of IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, validating that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 389 IIT gene products are drug-targetable with established or repurposed drugs. Among our results, we found 40 known and 349 novel lupus targets, along with 151 known and 238 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. We anticipate the IIT algorithm and shared and contrasting gene mechanisms uncovered here will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients.

Microneedle technology is a novel platform technology that revolutionizes ocular drug delivery and addresses critical challenges in the treatment of ocular diseases. Routine treatment methods, such as eye drops and intravitreal injections, suffer from low bioavailability and poor patient compliance. So, novel advanced platform technologies are required to overcome these challenges. Microneedle is a minimally invasive and promising alternative technique that helps precisely control drug delivery to targeted tissues and organs. This review investigates the potential impact of microneedle technology for eye care, underscoring recent advancements, underlying mechanisms, and emerging preclinical and clinical uses. Different types of microneedles, including solid, coated, dissolvable, and hollow, have demonstrated their potential and capability to bypass several barriers in the cornea and sclera. This ensures effective drug penetration and delivery. The current innovations in material science and fabrication methods have enhanced the safety and efficacy of microneedles, reducing discomfort and the chances of infections. These microneedle technologies offer sustained and controlled drug delivery, which could improve therapeutic outcomes for various disease conditions like age-related macular degeneration, glaucoma, diabetic neuropathy, etc. In the current review, recent preclinical and clinical studies emphasize microneedle-based ocular drug delivery's feasibility and potential benefits. These include improved pharmacokinetics, reduced dosing frequency, enhanced patient adherence, and, most importantly, microneedles offer versatile platforms for delivering a wide range of small and large molecules and gene therapies. Despite the exciting progress, obstacles such as regulatory barriers, scalability, and long-term biocompatibility persist. It will be essential to tackle these challenges through interdisciplinary research and partnerships to integrate microneedle technology into standard clinical use effectively. Ultimately, microneedle drug delivery offers a revolutionary method that has the potential to significantly enhance the treatment and results of ocular diseases, marking the dawn of a new era in eye care.

The pharmacological effects of the fruiting body of Ophiocordyceps sinensis (Os) exerted antioxidant, anti-virus, and immunomodulatory, whereas the anti-inflammatory effects and active components of Os mycelial submerged culture (OMSC) are not known. This study aimed to investigate the active compounds in the fermented liquid (FLOS), hot water (WEOS), and 50-95% (EEOS-50, EEOS-95) ethanol extracts of OMSC and their anti-inflammatory effects and potential mechanisms in LPS-stimulated microglial BV2 cells. The results demonstrated that all of the OMSC extracts could inhibit NO production in BV2 cells. EEOS-95 exhibited the strongest inhibitory effects (41 % inhibitory ability at 500 µg/mL), and its ergosterol, GABA, total phenolic, and total flavonoid contents were significantly higher than those of the other extracts (18.60, 18.60, 2.28, and 2.14 mg/g, p &lt; 0.05, respectively). EEOS-95 also has a strong inhibitory ability against IL-6, IL-1β and TNF-α with IC50 of 617, 277 and 507 µg/mL, respectively, which is higher than that of 1 mM melatonin. The anti-inflammatory mechanism of EEOS-95 seems to be associated with up-regulation of PPAR-γ/Nrf-2/HO-1 antioxidant-related expression and down-regulation of NF-κB/COX-2/iNOS pro-inflammatory expression signaling. Therefore, we hypothesized that EEOS-95 can prevent neurodegenerative diseases, but the effect on the application in vivo should be further investigated.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

Plant leaf area index (LAI) is a key characteristic affecting field canopy microclimate. In addition to traditional professional measuring instruments, smartphone camera sensors have been used to measure plant LAI. However, when smartphone methods were used to measure conifer forest LAI, very different performances were obtained depending on whether the smartphone was held at the zenith angle or at a 57.5° angle. To validate further the potential of smartphone sensors for measuring conifer LAI and to find the limits of this method, this paper reports the results of a comparison of two smartphone methods with an LAI-2000 instrument. It is shown that both methods can be used to reveal the conifer leaf-growing trajectory. However, the method with the phone oriented vertically upwards always produced better consistency in magnitude with LAI-2000. The bias of the LAI between the smartphone method and the LAI-2000 instrument was explained with regard to four aspects that can affect LAI: gap fraction, leaf projection ratio, sensor field of view (FOV), and viewing zenith angle (VZA). It was concluded that large FOV and large VZA cause the 57.5° method to overestimate the gap fraction and hence underestimate conifer LAI, especially when tree height is greater than 2.0 m. For the vertically upward method, the bias caused by the overestimated gap fraction is compensated for by an underestimated leaf projection ratio.

Leishmaniasis are neglected diseases that affect regions such as South Asia, South Africa and Latin America, less developed regions. Current treatment, for cutaneous, mucocutaneous and visceral leishmaniosis, which are the main forms of the disease, is based on the administration of pentavalent antimonial and amphotericin B. However, these drugs have low efficacy and high toxicity. For this reason, the search for new treatments for this disease is necessary, based on studies of new molecules and their conformations. The research proposed the conformational study of brominated guanidine compounds with potential antileishmanial activity using Nuclear Magnetic Resonance (NMR) and X-ray diffraction (XRD) techniques. The present study involves the bro-minated molecules, LQOF-G2, LQOF-G30, LQOF-G35 and LQOF-G35-Br. The later was synthesized by the reaction of LQOF-G35 with NBS under IR irradiation at 120 Watts of potency and dichloro-methane as solvent by 12-h of exposition. The obtained results demonstrated the efficiency of the bromination method, since two bromines atoms entered the molecule. Furthermore, NMR analysis showed the occurrence of a conformational change from Z to E when compound LQOF-G35 was brominated to LQOF-G35-Br. This feature was well confirmed by comparative DRX study of the LQOF-G35 and LQOF-G35-Br compounds. The antileishmanial activity of LQOF-G2 e LQOF-G35 motivated the synthesis of new brominated compounds LQOF-G30 e LQOF-G35-Br.

Wheat straw (WS) is a promising substrate for biogas production by anaerobic digestion (AD) due to its high carbohydrate content. An estimated 0.603 million t yr-1 of WS are generated from wheat production systems in South Africa. This is equivalent to an energy potential of 11 PJ. Despite, WS is still undervalued as a bioenergy resource in South Africa due to its structural complexity and low nitrogen content. WS disposal methods, such as use in livestock bedding, burning and burying into the soil, inter alia, are not sustainable and may contribute to global warming and climate change. Commercialization of the AD of WS needs to be further developed and promoted. Pre-treatment (i.e. physical, chemical, biological and hybrid methods) and anaerobic co-digestion (AcoD) are novel strategies that can support the conversion of WS into biogas and other value-added products. Current and future research should focus on optimizing pre-treatment and AcoD conditions towards industrialization of WS into valuable products. This paper focuses on the potential use of WS for biogas production by AD in South Africa. The aim is to create information that will promote research and development, and encourage policy makers and stakeholder participation and investment in WS biogas technology.

The superharmonic imaging of tissue has the potential for high spatial and contrast resolutions, compared to the fundamental and second harmonic imaging. For this technique, the spectral bandwidth of an ultrasound transducer is divided for transmission of ultrasound and reception of its superharmonics (i.e., higher than the second harmonic). Due to the spectral division for the transmission and reception, transmitted ultrasound energy is not sufficient to induce superharmonics in media without using contrast agents, and it is difficult that a transducer has a -6-dB fractional bandwidth of higher than 100%. For the superharmonic imaging of tissue, thus, multi-frequency array transducers are the best choice if available; transmit and receive elements are separate and have different center frequencies. However, the construction of a multi-frequency transducer for intravascular ultrasound (IVUS) imaging is particularly demanding because of its small size of less than 1 mm. Here, we report a recently developed dual-element focused IVUS transducer for the third harmonic imaging of tissue, which consists of a 35-MHz element for ultrasound transmission and a 105-MHz element for third harmonic reception. For high quality third harmonic imaging, both elements were fabricated to have the same focus at 2.5 mm. The results of tissue mimicking phantom tests demonstrated that the third harmonic images produced by the developed transducer had higher spatial resolution and deeper imaging depth than the fundamental images.

Since the mid-1990s probiotics have been proven to support the treatment of several gastrointestinal diseases. Additionally, probiotics have been taken as a common panacea for civilization diseases. To date, the only probiotic yeasts with evidence of health-promoting effects are Saccharomyces cerevisiae var. boulardii. The probiotic properties are strain-dependent, whereby it is crucial to develop methods to verify the probiotic-enriched food authentication including the growing number of dietary supplements with simplified commercialisation procedures. Due to the significant genetic similarity of S. cerevisiae var. boulardii to S. cerevisiae, qPCR-HRM analysis was tested, which has a very high sensitivity for polymorphism detection and enables simultaneous identification of the microorganism in the presence of the reference sample. The effectiveness of interspecies primer pairs and intragenus primer pairs designed to amplify heterogeneous regions was examined. HRM analysis using primers for 18SrRNA and ITS allowed for identification of S. cerevisiae var. boulardii at the species level. S. cerevisiae var. boulardii was efficiently identified at the variety level with amplification of HO and RPB2 in the single- and multi-component DNA extracts. The RPB2 amplicon showed the highest intraspecies differentiation power. The predominance of S. cerevisiae var. boulardii in the mixtures tested was crucial for identification using qPCR-HRM analysis and quantitatively corresponded to the strain content in the probiotic-enriched food matrices.

Obesity poses significant challenges in rural communities worldwide due to limited resources and healthcare access. Practical, innovative, and culturally sensitive approaches are essential. Time-Restricted Eating (TRE), aligning food intake with circadian rhythms, emerges as a promising strategy. By restricting eating to specific time windows, TRE synchronizes with the body's internal clock, offering potential metabolic health benefits. This review examines TRE's potential in rural obesity management, highlighting its simplicity and scalability. While TRE may address rural health disparities, cultural considerations and challenges such as undernutrition must be acknowledged for effective implementation. Overall, TRE shows promise in improving metabolic health and well-being in rural populations.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

The DEAD-box RNA helicase DDX3X is a multifunctional protein involved in RNA metabolism and stress responses. In this study, we investigated the role of RG/RGG motifs in the dynamic process of liquid-liquid phase separation (LLPS) of DDX3X using cell-free assays and explored their potential link to cancer development through bioinformatic analysis. Our results demonstrate that the number, location, and composition of RG/RGG motifs significantly influence the ability of DDX3X to undergo phase separation and form self-aggregates. Mutational analysis revealed that the spacing between RG/RGG motifs and the number of glycine residues within each motif are critical factors in determining the extent of phase separation. Bioinformatic analysis of cancer genomic datasets uncovered a significant enrichment of DDX3X mutations in RG/RGG motifs across multiple cancer types, particularly in the N-terminal region of the protein. Furthermore, we found that DDX3X is co-expressed with the stress granule protein G3BP1 in several cancer types and can undergo co-phase separation with G3BP1 in a cell-free system, suggesting a potential functional interaction between these proteins in phase-separated structures. DDX3X and G3BP1 may interact through their RG/RGG domains and subsequently exert important cellular functions under stress situation. Collectively, our findings provide novel insights into the role of RG/RGG motifs in modulating DDX3X phase separation and their potential contribution to cancer pathogenesis.

Clusterin (CLU) protein is involved in various pathophysiological processes including carcinogenesis and tumor progression. In recent years, the role of the secretory isoform has been demonstrated in tumor cells, where it inhibits apoptosis and favors the acquisition of resistance to conventional treatments used to treat cancer. To determine the possible therapeutic potential of inhibiting this protein, numerous studies have been carried out in this field. In this paper, we show the existing knowledge on the inhibition of this protein in different types of cancer and discuss the importance it could have in the development of new therapies directed against this pathology.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risks of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria, organelle where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At present, the exploration of novel therapies for alleviating diabetic neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect of sildenafil (phosphodiesterase-5 inhibitor) – metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats; (2) Methods: The study comprised a cohort of 70 diabetic rats and 10 non-diabetic rats which were submitted to hot, cold, and tactile stimulus tests. Morover, we investigated the influence of this combination on TNF-α, IL-6 nitrites and thiols levels in brain and liver tissues; (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in von Frey test, Hot-plate test and Cold-plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect in alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.