A Comprehensive Computational Screening of Phytochemicals Derived from Saudi Medicinal Plants against Human CC Chemokine Receptor 7 to Identify Potential Anti-Cancer Therapeutics

Homeostatic trafficking of immune cells by CC chemokine receptor 7 (CCR7) keeps immune responses and tolerance in a balance. The involvement of this protein in lymph node metastasis in cancer marks CCR7 as a penitential drug target. Using the crystal structure of CCR7, herein, a comprehensive virtual screening study is presented to filter novel strong CCR7 binding phytochemicals from Saudi medicinal plants that have a higher binding affinity for the intracellular allosteric binding pocket. By doing so, three small natural molecules named as Hit-1 (1,8,10-trihydroxy-3-methoxy-6-methylanthracen-9(4H)-one), Hit-2 (4-(3,4-dimethoxybenzyl)-3-(4-hydroxy-3-methoxybenzyl)dihydrofuran-2(3H)-one), and Hit-3 (10-methyl-12,13-dihydro-[1,2]dioxolo[3,4,5-de]furo[3,2-g]isochromeno[4,3-b]chromen-8-ol) are predicted showing strong binding potential for the CC chemokine receptor 7 allosteric pocket. During molecular dynamics simulations, the compounds were observed in the formation of several chemical bonding of short bond distances. Additionally, the molecules remained in strong contact with the active pocket residues and experienced small conformation changes that seemed to be mediated by the CCR7 loops to properly engage the ligands. Two types of binding energy methods (MM/GBPBSA and WaterSwap) were additionally applied to further validate docking and simulation findings. Both analyses complement the good affinity of compounds for CCR7, the electrostatic and van der Waals energies being the most dominant in intermolecular interactions. The active pocket residue’s role in compounds binding was further evaluated via alanine scanning, which highlighted their importance in natural compounds binding. Additionally, the compounds fulfilled all drug-like rules: Lipinski, Ghose, Veber, Egan, and Muegge passed many safety parameters, making them excellent anti-cancer candidates for experimental testing.     

A DPL model of photothermal interaction in a semiconductor material

The generalized model for plasma, thermal, and elastic waves under dual phase lag model have been applied to determine the carrier density, the displacement, the temperature, and the stresses in a semiconductor medium. Using Laplace transform and the eigenvalue approach methodology, the solutions of all variables have been obtained analytically. A semiconducting material like as silicon was considered. The results were graphically represented to show the different between the dual phase model, Lord and Shulman’s theory and the classical dynamical coupled theory.     

Effects of photodynamic therapy evaluated in a novel three-dimensional squamous cell carcinoma organ construct of the skin

Squamous cell carcinoma (SCC) of the skin is a malignant neoplasm that occurs in all ethnic groups primarily due to chronic sun exposure and constitutes a major health problem worldwide. Novel therapies for SCC are in development but as yet no in vitro models capable of screening these therapies and their mechanism of action before proceeding to clinical trials in human subjects have emerged. For this reason we have developed and characterized a novel three-dimensional human SCC construct and validated it using photodynamic therapy (PDT), a well-established modality for treating in situ SCCs. Histologic and immunohistochemical characterization of these SCC constructs revealed epidermal and dermal de-differentiation, increased cell proliferation and expression of immunohistochemical markers specific for cutaneous SCC. Application of PDT to these constructs led to tumor regression with widespread apoptosis and necrosis within 5 days. This in vitro model consistently reproduces the tumor development and dynamics of growing SCCs in vivo and provides a useful approach for screening new treatment modalities for this form of cutaneous cancer.     

Electroosmosis-modulated bio-flow of nanofluid through a rectangular peristaltic pump induced by complex traveling wave with zeta potential and heat source

Electrokineticmicroperistaltic pumps are important biomechanical devices that help in targeted drugging of sick body parts. This article is focused on mathematical modeling and analysis of some important aspect of such flows in a rectangular duct with wall properties. Effects of zeta potential, heat source, and deby length are also studied. Carbon nanotubes (CNTs) in the Newtonian base fluid are assumed as drugging material. A comparison of single-walled CNTs and multiwalled CNTs is also presented. It is considered that the walls are flexible and encapsulating the region with limited permeability. The defined flow problem is modeled and analyzed analytically for the transport of CNT–water nanofluid. It is accepted that the flow is steady, nonturbulent, and propagating waves do have a considerably longer wavelength when compared to amplitude. The conditions and assumptions lead to a model of coupled partial differential equations of order two. The exact results using the eigenfunction expansion method are procured and shown accordingly. The predictions about the behavior of important parameters are displayed for single-walled CNT and multiwalled CNT—water nanofluidic behavior—using figures. The impact of sundry parametersis are analyzed. The application of the current study involved a transporting/targeted drug delivery system using peristaltic micropumps and magnetic fields in pharmacological engineering.     

A Model for Evaluating and Determining the Most Appropriate Polymer Matrix Type for Natural Fiber Composites

The process of determining the proper polymer matrix type, using a wide range of criteria, to form a natural fiber–reinforced polymer composite is still not established enough. This work introduces, for the first time, a model to select the proper polymer matrix type for natural fibers to enhance the sustainability of the automotive industry. The model was developed to rank different polymers and to determine their relative merits considering 20 different criteria simultaneously, including different physical, mechanical, chemical, environmental, and technical criteria. This work can support establishing a road map for proper selection of polymers in different engineering applications as well as increasing the reliability of the polymer selection process.     

Evaluating the effects of estradiol on endothelial nitric oxide stimulated by erythrocyte-derived ATP using a microfluidic approach

Recently, estrogens have been reported to have protective effects against experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Although the molecular mechanism for such a protective effect is currently incomplete, we hypothesized that estradiol may reduce the release of ATP from erythrocytes (ERYs), thereby lowering the production of nitric oxide (NO) by endothelial cells. Here, we report on the use of a microfluidic device to investigate the direct effects of the estrogen estradiol on endothelial cell nitric oxide production. In addition, the incorporation of a thin polycarbonate membrane into the device enabled the passage of ERYs through the device to determine indirect effects of estradiol on NO production that may be meditated by ERYs. When these ERYs were incubated with increasing concentrations of estradiol, the NO production from the endothelial cells was attenuated to a value that was only 59 ± 7% of ERYs in the absence of estradiol. This decrease in NO production coincides with reductions in ERY-derived ATP release in the presence of estradiol. Estradiol is typically reported to have NO-stimulating effects; however, such reports have employed in vitro experimental designs that include only a single cell type. To demonstrate the potential importance of this attenuation of ATP from ERYs, results from a small-scale study show that the ATP release obtained from healthy controls was 138 ± 21 nM (n = 18) while the release from the ERYs obtained from people with MS was 375 ± 51 nM (n = 11). The studies reported here involving multiple cells types (endothelial cells and ERYs) may lead to a reappraisal of the in vivo activities of estradiol.     

A Quantum Crystal with Multidimensional Anharmonic Oscillators

The quantum anharmonic crystal is made up of a large number of multidimensional anharmonic oscillators arranged in a periodic spatial lattice with a nearest neighbor coupling. If the coupling coefficient is sufficiently small, then there is a convergent expansion for the ground state of the crystal. The estimates on the convergence are independent of the size of the crystal. The proof uses the path integral representation of the ground state in terms of diffusion processes. The convergence of the cluster expansion depends on the ergodicity properties of these processes.     

Self-error-rejecting photonic qubit transmission in polarization-spatial modes with linear optical elements

We present an original self-error-rejecting photonic qubit transmission scheme for both the polarization and spatial states of photon systems transmitted over collective noise channels. In our scheme, we use simple linear-optical elements, including half-wave plates, 50:50 beam splitters, and polarization beam splitters, to convert spatial-polarization modes into different time bins. By using postselection in different time bins, the success probability of obtaining the uncorrupted states approaches 1/4 for single-photon transmission, which is not influenced by the coefficients of noisy channels. Our self-error-rejecting transmission scheme can be generalized to hyperentangled n-photon systems and is useful in practical high-capacity quantum communications with photon systems in two degrees of freedom.     

Efficient Entanglement Concentration of Nonlocal Two-Photon Polarization-Time-Bin Hyperentangled States

We present two different hyperentanglement concentration protocols (hyper-ECPs) for two-photon systems in nonlocal polarization-time-bin hyperentangled states with known parameters, including Bell-like and cluster-like states, resorting to the parameter splitting method. They require only one of two parties in quantum communication to operate her photon in the process of entanglement concentration, not two, and they have the maximal success probability. They work with linear optical elements and have good feasibility in experiment, especially in the case that there are a big number of quantum data exchanged as the parties can obtain the information about the parameters of the nonlocal hyperentangled states by sampling a subset of nonlocal hyperentangled two-photon systems and measuring them. As the quantum state of photons in the time-bin degree of freedom suffers from less noise in an optical-fiber channel, these hyper-ECPs may have good applications in practical long-distance quantum communication in the future.