Molecular Docking of Phytochemicals against Streptococcus mutans Virulence Targets: A Proteomic Insight into Drug Planning

Streptococcus mutans (S. mutans) is the most prevalent and most associated with dental caries. Here we aim to identify, through an in silico study, potential bioactive molecules against S. mutans. Twenty-four bioactive molecules with proven action against S. mutans were selected: 1-methoxyficifolinol; 5,7,2′,4′-tetrahydroxy-8-lavandulylflavanone (sophoraflavanone G); 6,8-diprenylgenistein; apigenin; artocarpesin; artocarpin; darbergioidin; dihydrobiochanin A; dihydrocajanin (5,2′,4′-trihydroxy-7-methoxyisoflavanone); erycristagallin; Erystagallin; ferreirin; fisetin; kaempferol; licoricidin; licorisoflavan A; licorisoflavan C; licorisoflavan E; luteolin (3′,4′,5,7-tetrahydroxyflavone); malvidin-3,5-diglucoside; myricetin; orientanol B; quercetin; and quercitrin. Moreover, we selected nine important target proteins for the virulence of this microorganism to perform as drug targets: antigen I/II (region V) (PDB: 1JMM); Antigen I/II (carbox-terminal region) (PDB: 3QE5); Spap (PDB: 3OPU); UA159sp signaling peptide (PDB: 2I2J); TCP3 signaling peptide (PDB: 2I2H); ATP-binding protein ComA (PDB: 3VX4); glucanosucrase (PDB: 3AIC); dextranase (PDB: 3VMO), and Hemolysin (PDB: 2RK5). Five molecules were revealed to be the best ligands for at least three target proteins, highlighting the following compounds: 11 (erystagallin), 10 (erycristagallin), 1 (methoxyficifonilol), 20 (malvidin-3,5-diglucoside), and 2 (sophoraflavanone G), which indicates a possible multi-target action of these compounds. Therefore, based on these findings, in vitro and in vivo tests should be performed to validate the effectiveness of these compounds in inhibiting S. mutans virulence factors. Furthermore, the promising results of these assays will allow the incorporation of these phytoconstituents in products for oral use for the control of tooth decay.

Research on Human Motion Analysis in Moving Scene Based on Timing Detection and Video Description Algorithm

Technical movement analysis requires specialized domain knowledge and processing a large amount of data, and the advantages of AI in processing data can improve the efficiency of data analysis. In this paper, we propose a feature pyramid network-based temporal action detection (FPN-TAD) algorithm, which is used to solve the problem that the action proposal module has a low recall rate for small-scale temporal target action regions in the current video temporal action detection algorithm research. This paper is divided into three parts. The first part is an overview of the algorithm; the second part elaborates the network structure and the working principle of the FPN-TAD algorithm; and the third part gives the experimental results and analysis of the algorithm.

Trazodone succinate — new opportunities for pharmacological correction of situational behavioral abnormalities in dogs and cats

Currently, the interest of veterinarians and owners in the pharmacological correction of situational behavioral disorders in companion animals has increased significantly. To quickly correct deviant behavior in dogs and cats, veterinarians use some of the psychotropic drugs used in humane medicine, in particular, trazodone, an antidepressant antagonist / serotonin reuptake inhibitor. Based on the analysis of literature sources, data on the history of creation and pharmacological properties, assessment of the safety and efficacy of drugs based on trazodone hydrochloride in behavioral medicine of small pets are provided. The data on the prerequisites for the development, pharmaco-toxicological and clinical evaluation of a new drug for the modification of abnormal behavior in dogs and cats, Express Uspokoin® tablets based on trazodone succinate, which, with a high efficiency of the target action, made it possible to achieve the absence of side effects and significantly increase the tolerance of the dosage form by animals, are analyzed. compared with preparations based on trazodone hydrochloride.

Clove Constituents as new leads for the Design and development of Multi-targeted Anti-Alzheimer activity

Objective: To use virtual screening analysis to screen out the phytoconstituents of Syzygium aromaticum against multiple targets of AD and determine its anti-oxidant and inflammatory inhibitory property. Methods: The compounds listed out from Syzygium aromaticum were subjected to virtual screening based on their drug likeness property and bioactivity scores. The molecular docking simulation such as HEX 8.0, PyRx, MVD along with Auto Dock 4.2 were employed to determine the potential candidate for providing activity against multiple targets of AD. The toxicity estimation was also carried out using TEST software. The potential candidate was further evaluated using DPPH, FRAT, Albumin denaturation and Proteinase inhibition method. Results: Only eight phytoconstituents were selected for virtual screening as they possessed drug likeness property and better bioactivity score for inhibition of kinases, proteases and enzymes. The docking results from various tools predicted that Oleanolic acid can be considered as potential constituents for multi-target action against AD. Toxicity estimation was in range. It also exhibited anti-oxidant and inflammatory inhibition providing its evidence for anti-AD activity. Conclusion: Taken together, these virtual screening results and in-vitro assays suggest that Oleanolic acid has multi target action against AD, which can be proved further with in-vivo studies.

Deep Learning-Based Multitarget Motion Shadow Rejection and Accurate Tracking for Sports Video

The effect is tested in various specific scenes of sports videos to complete the multitarget motion multitarget tracking detection application applicable to various specific scenes within sports videos. In this paper, deep neural networks are applied to sports video multitarget motion shadow suppression and accurate tracking to improve tracking performance. After the target frame selection is determined, the tracker uses an optical flow method to estimate the limits of the target sports video multitarget motion based on the sports video multitarget motion of the target object between frames. The detector first scans each sports video image frame one by one, observing the previously discovered and learned image frame subregions one by one until the current moment that is highly like the target to be tracked. The preprocessed remote sensing images are converted into grayscale images, the histogram is normalized, and the appropriate height threshold is selected in combination with the regional growth function to realize the rejection of sports video multitarget motion shadow and establish the sports video multitarget network model. The distance and direction of the precise target displacement are determined by frequency-domain vectors and null domain vectors, and the target action judgment mechanism is formed by decision learning. Finally, comparing with other shadow rejection and precision tracking algorithms, the proposed algorithm achieves greater advantages in terms of accuracy and time consumption.

Engaging People with Energy Efficiency: A Randomised Controlled Trial Testing the Effects of Thermal Imaging Visuals in a Letter Communication

The study tested the effect of adding visualisations to a communication to engage householders with an energy efficiency programme. External wall insulation is an appropriate way of insulating homes, yet take-up is low. Householders may be unaware of the heat loss from uninsulated walls. In earlier research, seeing thermal images prompted the uptake of simple energy efficiency actions amongst householders. Thermal images were added to a standard letter to visualise heat transfer from a home before and after external wall insulation had been installed. A randomised controlled trial tested three types of letter (standard, standard plus thermal image showing problem, standard plus thermal images showing problem and solution) in 5483 UK households. The target outcome was the rate of telephone enquiries after exposure to the letters. Enquiry rates were low (1.6%) and did not differ between letter type. We discuss the null effect in relation to the target action (external wall insulation), the manner of presentation of the visuals (mass communication, letter through the door) and the ingredients of a persuasive intervention. Findings suggest that taking a key ingredient from an intervention and applying it in a different context may result in the loss of its impact.

Bruton’s Tyrosine Kinase Inhibitors Ibrutinib and Acalabrutinib Counteract Anthracycline Resistance in Cancer Cells Expressing AKR1C3

Over the last few years, aldo-keto reductase family 1 member C3 (AKR1C3) has been associated with the emergence of multidrug resistance (MDR), thereby hindering chemotherapy against cancer. In particular, impaired efficacy of the gold standards of induction therapy in acute myeloid leukaemia (AML) has been correlated with AKR1C3 expression, as this enzyme metabolises several drugs including anthracyclines. Therefore, the development of selective AKR1C3 inhibitors may help to overcome chemoresistance in clinical practice. In this regard, we demonstrated that Bruton’s tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib efficiently prevented daunorubicin (Dau) inactivation mediated by AKR1C3 in both its recombinant form as well as during its overexpression in cancer cells. This revealed a synergistic effect of BTK inhibitors on Dau cytotoxicity in cancer cells expressing AKR1C3 both exogenously and endogenously, thus reverting anthracycline resistance in vitro. These findings suggest that BTK inhibitors have a novel off-target action, which can be exploited against leukaemia through combination regimens with standard chemotherapeutics like anthracyclines.

Phytotoxicity, Morphological, and Metabolic Effects of the Sesquiterpenoid Nerolidol on Arabidopsis thaliana Seedling Roots

Natural herbicides that are based on allelopathy of compounds, can offer effective alternatives to chemical herbicides towards sustainable agricultural practices. Nerolidol, a sesquiterpenoid alcohol synthesized by many plant families, was shown to be the most effective allelopathic compound in a preliminary screening performed with several other sesquiterpenoids. In the present study, Arabidopsis thaliana seedlings were treated for 14 d with various cis-nerolidol concentrations (0, 50, 100, 200, 400, and 800 µM) to investigate its effects on root growth and morphology. To probe the underlying changes in root metabolome, we conducted untargeted gas chromatography mass spectrometry (GC-MS) based metabolomics to find out the specificity or multi-target action of this sesquiterpenoid alcohol. Oxidative stress (measured as levels of H2O2 and malondialdehyde (MDA) by-product) and antioxidant enzyme activities, i.e., superoxide dismutase (SOD) and catalase (CAT) were also evaluated in the roots. Nerolidol showed an IC50 (120 µM), which can be considered low for natural products. Nerolidol caused alterations in root morphology, brought changes in auxin balance, induced changes in sugar, amino acid, and carboxylic acid profiles, and increased the levels of H2O2 and MDA in root tissues in a dose-dependent manner. Several metabolomic-scale changes induced by nerolidol support the multi-target action of nerolidol, which is a positive feature for a botanical herbicide. Though it warrants further mechanistic investigation, nerolidol is a promising compound for developing a new natural herbicide.