QSAR and DFT Studies of Some Tacrine-Hydroxamate Derivatives as Inhibitors of Cholinesterase (AChEs) in the Treatment of Alzheimer's Disease

Introduction: This work was devoted to an in silico investigation conducted on twenty-eight Tacrine-hydroxamate derivatives as a potential treatment for Alzheimer's disease using DFT and QSAR modeling techniques. Method(s): The data set was randomly partitioned into a training set (22 compounds) and a test set (6 compounds). Then, fourteen models were built and were used to compute the predicted pIC50 of compounds belonging to the test set. Result(s): Al built models were individualy validated using both internal and external validation methods, including the Y-Randomization test and Golbraikh and Tropsha's model acceptance criteria. Then, one model was selected for its higher R2, R2test, and Q2cv values (R2 = 0.768, R2adj = 0.713, MSE = 0.304, R2test=0.973, Q2cv = 0.615). From these outcomes, the activity of the studied compounds toward the main protease of Cholinesterase (AChEs) seems to be influenced by 4 descriptors, i.e., the total dipole moment of the molecule (mu), number of rotatable bonds (RB), molecular topology radius (MTR) and molecular topology polar surface area (MTPSA). The effect of these descriptors on the activity was studied, in particular, the increase in the total dipole moment and the topological radius of the molecule and the reduction of the rotatable bond and topology polar surface area increase the activity. Conclusion(s): Some newly designed compounds with higher AChEs inhibitory activity have been designed based on the best-proposed QSAR model. In addition, ADMET pharmacokinetic properties were carried out for the proposed compounds, the toxicity results indicate that 7 molecules are nontoxic.Copyright © 2023 Bentham Science Publishers.

Stokes-Mueller polarization-based analysis of model SARS-CoV-2 virions.

Understanding the virology of the coronavirus at the structural level has gained utmost importance to overcome the constant and long-term health complications induced by them. In this work, the light scattering properties of SARS-CoV-2 of size 140 nm were simulated by using discrete dipole approximation (DDA) for two incident wavelengths 200 nm and 350 nm, respectively. Three different 3-dimensional (3D) models of SARS-CoV-2 corresponding to 15, 20, and 40 numbers of spike proteins on the viral capsid surface were constructed as target geometries for the DDA calculations. These models were assessed by employing Stokes-Mueller polarimetry to obtain individual polarization properties such as degree of polarization (DOP), degree of linear polarization (DOLP), and degree of circular polarization (DOCP). Irrespective of its spike numbers, all the coronavirus models were found to display higher DOP and DOCP values and negligibly small DOLP values for circularly polarized incident light, indicating the presence of chiral structures. On the other hand, the lack of understanding about the dependence of the Mueller matrix on its microstructural properties was overcome by transforming 16 Mueller elements into sub-matrices with specific structural and physical properties using Lu-Chipman-based Mueller matrix polar decomposition method. The obtained properties such as retardance, diattenuation, and depolarization were used for investigating the composition and microstructural information. The approach presented in this work has the potential to understand the virology of the coronavirus at the structural level and, therefore, will be beneficial in developing effective detection strategies by exploiting their characteristic electromagnetic scattering signatures.

IN VITRO STUDY OF THE EFFECT OF CYTOFLAVIN ON ERYTHROCYTES OF PATIENTS UNDERWENT COVID-19

Erythrocytes of 40 patients (11 men and 29 women, average age 52.2 +/- 13.2 years), COVID-19 convalescents (within 2 - 4 months after the disease), were studied by dielectrophoresis using an electro-optical cell detection system in a nonuniform alternating electric field. Cytoflavin at a concentration of 1:30 (v:v) after incubation with erythrocytes (1,6 - 1,8 x 108/ml) for 10 minutes caused an increase by 24 - 63% on average in the share of discocytes, amplitude of deformation, speed of cell movement towards electrodes, magnitude of the dipole moment, capacity of the erythrocyte membranes, and in the polarizability at a frequency of 106 Hz and relative polarizability (p = 0.05 - 0.0001). On the contrary, a decrease by 27 - 49% on average is observed in the composite indicators of viscosity, cell rigidity, electrical conductivity, aggregation index, degree of hemolysis at different frequencies of the electric field (p = 0.05 - 0.002). A shift of the crossover frequency of erythrocytes (from the position of the frequency regions of negative and positive dielectrophoresis) to the low-frequency range is revealed (p < 0.0001). The analysis of data using the Volcano-plot method (paired and unpaired statistics) showed that the degree of erythrocyte deformation at a frequency of 0.5 . 106 Hz, relative polarizability, the position of the crossover frequency, membrane capacity and polarizability of cells at different frequencies of the electric field appeared to be the most sensitive to the action of cytoflavin. Thus, the action of cytoflavin triggers the processes optimizig the rheological properties of erythrocytes of patients underwent COVID-19 which is rather important for adequate micro- and macrocirculation of blood and allows expanding indications for the use of the drug in patients of this category. Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

FEATURES OF THE PARAMETERS OF RED BLOOD CELLS AND HEMOSTASIS IN PATIENTS WITH STROKES ASSOCIATED WITH CORONAVIRUS INFECTION

Objective: The purpose is to identify the peculiarities of the parameters of red blood cells (RBC) and hemostasis in patients with strokes associated with coronavirus infection. Design and method: A total of 124 patients (48.5 + 1.9 years) with impairments of cerebral circulation due to COVID-19 (confirmed by positive PCR test) had been examined. Among them, 74 patients had ischemic stroke, 25- transient ischaemic attack, 17- intracerebral hemorrhage, 8- subarachnoid hemorrhage. The parameters of hemostasis were measured by standard methods, electrical, viscoelastic parameters of RBC - by dielectrophoresis. Results: 71 patients (the 1st group) showed signs of intravascular coagulation and thrombosis: accelerated platelet-leukocyte aggregation, increased levels of coagulation products, reduced fibrinolysis activity (p = 0.001-0.04). The levels of D-dimer, fibrinogen, ESR, platelet count were higher in this group compared to the second one (p < 0.01). A moderate increase of RBC summarized rigidity, viscosity was noted. The level of RBC hemolysis was associated with platelet count (r = 0.735,p = 0.03), D-dimer (r = 0.482, p < 0.05), fibrinogen level (r = 0.374, p = 0.04). In 2nd group (53 persons), the markers of thrombosis had moderate deviations. Sharply reduced RBC deformability with increased summarized rigidity, viscosity was dominant coupled with the background of high electrical conductivity of cell membranes compared to the indicators in the 1st group (p < 0.01). There was a decrease of membrane capacity, surface charge, cell dipole moment, polarizability than those in the 1st group (p = 0.0001-0.05). A sharp decrease of RBC deformability creates obstacles to overcoming small-diameter capillaries, leading to violations of microcirculatory blood flow. RBC deformability was associated with levels of ferritin (r = 0.451, p = 0.02), HbA1c (r = 0.480, p = 0.03), uric acid (r = -0.371, p < 0.05), LDL cholesterol (r = 0.461, p = 0.02). Incubation of blood samples in vitro for 10 min with riboflavin, nicotinamide, inosine, which ensures RBC energy metabolism, restored the reduced RBC deformability (p < 0.01), altered cell morphology (p = 0.04), decreased RBC aggregation (p < 0.001). Conclusions: The revealed features of parameters of RBC hemostasis in stroke patients with coronavirus infection are associated with two independent pathogenetic mechanisms: thrombotic and hemorheologic. The thrombotic variant is due to procoagulant state and an activity of inflammation. The hemorheologic variant is caused by decrease of RBC energy metabolism, activity of enzymes.

Adsorption of chloroquine and hydroxychloroquine as potential drugs for SARS-CoV-2 infection on BC3nanosheets: a DFT study

The adsorption of chloroquine (CQ) and hydroxychloroquine (HCQ) on BC3nanosheets was evaluated and compared in gas and water media. The most desired complexes were obtained when the drug is parallel to the BC3surface, with an adsorption energy of −1.69 and −1.77 eV for CQ/bare and CQ/hydrogenated BC3complexes, respectively. The corresponding adsorption energies for HCQ/bare and HCQ/hydrogenated BC3nanosheets are −1.78 and −1.99 eV, respectively. It was found that the BC3nanosheets could be a suitable carrier of CQ and HCQ drugs, considering the amount of adsorption energy in the gas phase and water environment. The hydrogenated BC3nanosheet is a more prominent nanocarrier for CQ and HCQ than the bare BC3monolayer.

Tailoring Resonant Energy Transfer Processes for Sustainable and Bio-Inspired Sensing

Dipole–Dipole interactions (DDI) constitute an effective mechanism by which two physical entities can interact with each other. DDI processes can occur in a resonance framework if the energies of the two dipoles are very close. In this case, an energy transfer can occur without the need to emit a photon, taking the name of Förster Resonance Energy Transfer (FRET). Given their large dependence on the distance and orientation between the two dipoles, as well as on the electromagnetic properties of the surrounding environment, DDIs are exceptional for sensing applications. There are two main ways to carry out FRET-based sensing: (i) enhancing or (ii) inhibiting it. Interaction with resonant environments such as plasmonic, optical cavities, and/or metamaterials promotes the former while acting on the distance between the FRET molecules favors the latter. In this review, we browse both the two ways, pointing the spotlight to the intrinsic interdisciplinarity these two sensing routes imply. We showcase FRET-based sensing mechanisms in a variety of contexts, from pH sensors to molecular structure measurements on a nano-metrical scale, with a particular accent on the central and still mostly overlooked role played between a nano-photonically structured environment and photoluminescent molecules.

Research of Electromagnetic Field Enhancement of Surface Plasmon Resonant Mode in Metal Nanosphere-Nanodisc Structure

Surface plasmon has a history of more than one hundred years since its birth and has been a brand new discipline-plasmonics. Localized surface plasmon in metal nanostructures can gain very strong near-surface electric field enhancement and has been applied to many types researches successfully. However, there is relatively less study of the interaction between localized surface plasmon and magnetic field in incident light. This paper calculates the near-surface electromagnetic field enhancement of metal nanosphere-nanodisc gap based on the previous achievement. This paper shows that under the excitation of the single tightly radially polarized optical beam, the metal nanodisc can produce localized surface plasmon breathing mode and electric dipole moment mode, which give rise to the longitudinal electric field enhancement at the nanodisc center. And then, because of the resonance interaction of the metal nanodisc and localized surface plasmon electric dipolar moment of the metal nanosphere, a gap mode of localized surface plasmon resonance with efficient longitudinal electric field enhancement can be produced. Through carrying out the numerical simulation, this paper demonstrates that the near-surface longitudinal electric field of metal nanostructure gap mode can obtain 250 times electrical field enhancement relative to the valid transverse electrical field that is used to excite the breathing mode, and the enhancement factor of near-surface magnetic field could be 170. In order to present more clearly the character of the spectrum and the near-surface electromagnetic field distribution of this new metal nanostructure, the near-surface electromagnetic field distribution and the resonant wavelengths of this new metal nanostructure are also studied. The calculation results show that the proposed metal nanosphere-nanodisc nanostructure owns an obvious advantage on the local near-surface electromagnetic field enhancement and a relatively large frequency spectrum. Due to the electromagnetic field enhancement advantage of the metal nanostructure proposed by this paper, the future is not without hope that the results here could be applied to more and more researches, especially biomedicine, and provide a bit of reference in order to fight for novel coronavirus. © 2022, Peking University Press. All right reserved.

A Self-Powered UHF Passive Tag for Biomedical Temperature Monitoring

Self-powered RF passive sensors have potential application in temperature measurements of patients with health problems. Herein, this work presents the design and implementation of a self-powered UHF passive tag prototype for biomedical temperature monitoring. The proposed battery-free sensor is composed of three basic building blocks: a high-frequency section, a micro-power management stage, and a temperature sensor. This passive temperature sensor uses an 860 MHz to 960 MHz RF carrier and a 1 W Effective Isotropic Radiated Power (EIRP) to harvest energy for its operation, showing a read range of 9.5 m with a 13.75 µW power consumption, and an overall power consumption efficiency of 10.92% was achieved. The proposed device can measure temperature variations between 0 °C and 60 °C with a sensitivity of 823.29 Hz/°C and a standard error of 13.67 Hz/°C over linear regression. Circuit functionality was validated by means of post-layout simulations, characterization, and measurements of the manufactured prototype. The chip prototype was fabricated using a 0.18 µm CMOS standard technology with a silicon area consumption of 1065 µm × 560 µm. The overall size of the self-powered passive tag is 8 cm × 2 cm, including both chip and antenna. The self-powered tag prototype could be employed for human body temperature monitoring.

All-textile inspired-folded dipole antennas for on/off-body communications medical applications

Two textile-based printed inspired Folded Dipole Antennas (FDAs) are presented in this paper for health monitoring of Covid-19 infected patients. The first antenna has an overall size of 80 mm × 20 mm and is mounted on the human's chest, while the second one is backed by a 2 × 4 textile Artificial Magnetic Conductor (AMC) array structure and is mounted on a surgical mask that covers the human’s mouth. The first antenna is designed to work at center frequency, bandwidth, and gain of 2.45 GHz, 116.6 MHz and −2.45 dB, respectively. The second antenna works at 2.4 GHz with bandwidth of 76.6 MHz and gain of 2.71 dB. The SAR results equal 0.524 W/Kg and 0.255 W/Kg at 1 g and 10 g, respectively, for the first antenna and 0.0174 W/Kg and 0.0091 W/Kg, respectively, for the second one. The previous specifications of the two antennas enable them to be utilized in wearable applications and Wi-Fi services.

Single-Particle Characterization of SARS-CoV-2 Isoelectric Point and Comparison to Variants of Interest.

SARS-CoV-2, the cause of COVID-19, is a new, highly pathogenic coronavirus, which is the third coronavirus to emerge in the past 2 decades and the first to become a global pandemic. The virus has demonstrated itself to be extremely transmissible and deadly. Recent data suggest that a targeted approach is key to mitigating infectivity. Due to the proliferation of cataloged protein and nucleic acid sequences in databases, the function of the nucleic acid, and genetic encoded proteins, we make predictions by simply aligning sequences and exploring their homology. Thus, similar amino acid sequences in a protein usually confer similar biochemical function, even from distal or unrelated organisms. To understand viral transmission and adhesion, it is key to elucidate the structural, surface, and functional properties of each viral protein. This is typically first modeled in highly pathogenic species by exploring folding, hydrophobicity, and isoelectric point (IEP). Recent evidence from viral RNA sequence modeling and protein crystals have been inadequate, which prevent full understanding of the IEP and other viral properties of SARS-CoV-2. We have thus experimentally determined the IEP of SARS-CoV-2. Our findings suggest that for enveloped viruses, such as SARS-CoV-2, estimates of IEP by the amino acid sequence alone may be unreliable. We compared the experimental IEP of SARS-CoV-2 to variants of interest (VOIs) using their amino acid sequence, thus providing a qualitative comparison of the IEP of VOIs.