A comparative study to evaluate the effects of antibiotics, plant extracts and fluoride-based toothpaste on the oral pathogens isolated from patients with gum diseases in Pakistan

Oral diseases caused by various microorganisms are common around the world. Scientific research has now been focusing on novel medicines to overcome bacterial resistance and antibiotics side effects; therefore, the current study was designed to assess the efficacy of certain antibiotics, toothpaste, and medicinal plant extracts (Ajuga bracteosa and Curcuma longa) versus the bacterial pathogens isolated from the human oral cavity. A total of 130 samples were collected from Khyber Teaching Hospital Peshawar, Pakistan, among those 27 species isolated, and eight bacterial species were identified from the samples. Among all the bacterial species, Staphylococcus aureus (29.62%) and Proteus mirabilis (22.2%) were found to be more prevalent oral pathogens. In comparison, the least pervasive microbes were Proteus vulgaris, Shigella sonnei, Escherichia coli and Aeromonas hydrophila. The study also suggested that dental problems were more prevalent in males (41-50 years of age) than females. Among the eight antibiotics used in the study, the most promising results were shown by Foxicillin against A. hydrophila. The survey of TP1 revealed that it showed more potent antagonist activity against Proteus vulgaris as compared TP2 and TP3 that might be due to the high content of fluoride. The Curcuma longa showed more significant activity than Ajuga bracteosa (Stem, leaves and root) extracts. The data obtained through this study revealed that antibiotics were more effective for oral bacterial pathogens than toothpaste and plant extracts which showed moderate and low activity, respectively. Therefore, it is suggested that the active compounds in individual medicinal plants like Curcuma longa and Ajuga bracteosa could replace the antibiotics when used in daily routine as tooth cleansers or mouth rinses.

Virtual Combinatorial Library Screening of Quinadoline B Derivatives against SARS-CoV-2 RNA-Dependent RNA Polymerase

The unprecedented global health threat of SARS-CoV-2 has sparked a continued interest in discovering novel anti-COVID-19 agents. To this end, we present here a computer-based protocol for identifying potential compounds targeting RNA-dependent RNA polymerase (RdRp). Starting from our previous study wherein, using a virtual screening campaign, we identified a fumiquinazolinone alkaloid quinadoline B (Q3), an antiviral fungal metabolite with significant activity against SARS-CoV-2 RdRp, we applied in silico combinatorial methodologies for generating and screening a library of anti-SARS-CoV-2 candidates with strong in silico affinity for RdRp. For this study, the quinadoline pharmacophore was subjected to structural iteration, obtaining a Q3-focused library of over 900,000 unique structures. This chemical library was explored to identify binders of RdRp with greater affinity with respect to the starting compound Q3. Coupling this approach with the evaluation of physchem profile, we found 26 compounds with significant affinities for the RdRp binding site. Moreover, top-ranked compounds were submitted to molecular dynamics to evaluate the stability of the systems during a selected time, and to deeply investigate the binding mode of the most promising derivatives. Among the generated structures, five compounds, obtained by inserting nucleotide-like scaffolds (1, 2, and 5), heterocyclic thiazolyl benzamide moiety (compound 3), and a peptide residue (compound 4), exhibited enhanced binding affinity for SARS-CoV-2 RdRp, deserving further investigation as possible antiviral agents. Remarkably, the presented in silico procedure provides a useful computational procedure for hit-to-lead optimization, having implications in anti-SARS-CoV-2 drug discovery and in general in the drug optimization process.

Chemotherapy Combined With Recombinant Human Endostatin (Endostar) Significantly Improves the Progression-Free Survival of Stage IV Soft Tissue Sarcomas

PurposeOur previously study showed that recombinant human endostatin (Endostar) combined with chemotherapy had significant activity to increase the mPFS in patients with advanced sarcomas with tolerable side effects. However, the small cohort size and short follow-up time made it difficult to screen sensitive sarcoma subtypes and determine whether there is an overall survival benefit. With the largest sarcoma cohort to our knowledge, we try to confirm the efficacy and safety of chemotherapy combined with Endostar in stage IV sarcomas, with the specific purpose of finding out the sensitive sarcoma types for this combined treatment.MethodsAfter the exclusion of ineligible patients, 156 patients with stage IV bone and soft tissue sarcomas were included in this study according to the inclusion criteria.ResultsBy the end of follow-up, the ORR was 10.7% (9/84) vs 1.4% (1/72) (p=0.041), the DCR was 26.2% (22/84) vs 5.6% (4/72) (p=0.001) in the combined group and chemotherapy group, respectively. The mPFS of combined group was significantly longer than the chemotherapy group (10.42 vs 6.87 months, p=0.003). The mOS were 26.84 months and 23.56 months, without significant difference (p= 0.481). In osteogenic sarcoma, there was no statistically significant difference in the mPFS between the two groups (p=0.59), while in the soft tissue sarcoma, the mPFS in the combined group was significantly higher than that of the chemotherapy group (11.27 vs 8.05 months, p=0.004). Specifically, undifferentiated polymorphic sarcoma (UPS) was the possible sarcoma subtypes that benefited from the combined therapy. For the 38 UPS patients (28 patients in the combined group and 10 patients in the chemotherapy group), the mPFS in the combined group was up to 14.88 months, while it was only 7.1 months in the chemotherapy group, with a significant difference (p=0.006). The most common adverse events in the combined group were myelosuppression, gastrointestinal reactions and abnormal liver function, without significant difference in two groups.ConclusionChemotherapy plus Endostar could prolong mPFS and improve ORR and DCR in patients with stage IV soft tissue sarcoma, suggesting that the combined therapy could improve the patient prognosis in soft tissue sarcomas, especially the UPS patients.

In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron B.1.1.529 isolate

The emergence and rapid spread of the Omicron variant of SARS-CoV-2, which has more than 30 substitutions in the spike glycoprotein, compromises the efficacy of currently available vaccines and therapeutic antibodies. Using a clinical strain of the Omicron variant, we analyzed the neutralizing power of eight currently used monoclonal antibodies compared to the ancestral B.1 BavPat1 D614G strain. We observed that six of these antibodies have lost their ability to neutralize the Omicron variant. Of the antibodies still having neutralizing activity, Sotrovimab/Vir-7831 shows the smallest reduction in activity, with a factor change of 3.1. Cilgavimab/AZD1061 alone shows a reduction in efficacy of 15.8, resulting in a significant loss of activity for the Evusheld cocktail (42.6 fold reduction) in which the other antibody, Tixagevimab, does not retain significant activity against Omicron. Our results suggest that the clinical efficacy of the initially proposed doses should be rapidly evaluated and the possible need to modify doses or propose combination therapies should be considered.

Synthesis and biological evaluation of pyrazole analogues linked with 1,2,3-triazole and 4-thiazolidinone as antimicrobial agents

A new series of 2-[3-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-4-pyrazolyl]-3-aryl-1,3-thiazolan-4-one 5(a-i) have been designed, synthesized and evaluated for their in vitro antibacterial activity against Gram positive bacteria viz. Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538p), Micrococcus luteus (IFC 12708) and Gram negative bacteria viz. Proteus vulgaris (ATCC 3851), Salmonella typhimurium (ATCC 14028), Escherichia coli (ATCC 25922) the antifungal activity against Candida albicans (ATCC 10231), Aspergillus fumigatus (HIC 6094), Trichophyton rubrum (IFO 9185), Trichophyton mentagrophytes (IFO 40996). Antibacterial evaluation indicates that compounds containing 4-methoxyphenyl 5c, 4-fluorophenyl 5d and 2,5-difluorophenyl 5h groups on thiazolidinone ring showed significant activity equal to that of standard drug. The antifungal evaluation shows that compound 5c is highly active against A. fumigatus, compound 5d and 5h were also active against C. albicans and A. fumigatus.

Domain-Specific On-Device Object Detection Method

Object detection is a significant activity in computer vision, and various approaches have been proposed to detect varied objects using deep neural networks (DNNs). However, because DNNs are computation-intensive, it is difficult to apply them to resource-constrained devices. Here, we propose an on-device object detection method using domain-specific models. In the proposed method, we define object of interest (OOI) groups that contain objects with a high frequency of appearance in specific domains. Compared with the existing DNN model, the layers of the domain-specific models are shallower and narrower, reducing the number of trainable parameters; thus, speeding up the object detection. To ensure a lightweight network design, we combine various network structures to obtain the best-performing lightweight detection model. The experimental results reveal that the size of the proposed lightweight model is 21.7 MB, which is 91.35% and 36.98% smaller than those of YOLOv3-SPP and Tiny-YOLO, respectively. The f-measure achieved on the MS COCO 2017 dataset were 18.3%, 11.9% and 20.3% higher than those of YOLOv3-SPP, Tiny-YOLO and YOLO-Nano, respectively. The results demonstrated that the lightweight model achieved higher efficiency and better performance on non-GPU devices, such as mobile devices and embedded boards, than conventional models.

Populism in Robots

Populism has rarely been discussed in the context of robotics. This chapter will explore how intimate relationships, such as love and sex, between human and robots, will bring populism to the populist masses. Intimacy between humans and robots was first raised and discussed by David Levy in his book titled Love and Sex with Robotics published in 2007. As a result, the subject of human-robot romantic and intimate relationships rapidly developed into an academic research discipline in its own right. Since then, researchers have come up with many implementations of robot companions like sex robots, emotional robots, humanoid robots, and artificial intelligent systems that can simulate human emotions. This chapter presents a summary of significant activity in this field during the recent years, predicts how the field is likely to develop, and its ethical and legal background. They also discuss their research in physical devices for human-robot love and sex communication.

Developing Jurisprudential Inquiry Based Learning Model of Teaching Fiqh at Madrasah Tsanawiyah

Learning is the most significant activity in education. Through learning activities, the goals of education are achieved. Students’ success in learning mostly depends on their mastery to learn independently and on how they manage their study. The research aims to develop learning model at Madrasah Tsanawiyah, to make the learning process triggers students to be more creative and study better. The method used in the research refers to the nature of Research and Development. The steps of the study are preliminary study, development, and product test. The study found that the development of a jurisprudential inquiry-based learning model for learning Fiqh helps students to improve their learning outcomes. The model has significantly proven effective to support students’ behavior change, thus their achievement increases.

Synthesis and Characterisation of Cobalt Ferrite Coatings for Oxygen Evolution Reaction

In this paper, two novel procedures based on powder sedimentation, thermal treatment, and galvanostatic deposition were proposed for the preparation of porous cobalt ferrite (CoFe2O4) coatings with a metallic and organic binder for use as catalysts in the oxygen evolution reaction (OER). The electrochemical properties of the obtained electrode materials were determined as well, using both dc and ac methods. It was found that cobalt ferrite coatings show excellent electrocatalytic properties towards the oxygen evolution reaction (OER) with overpotential measured at a current density of 10 mAcm−2 from 287 to 295 mV and a Tafel slope of 35–45 mVdec−1. It was shown that the increase in the apparent activity of the CoFe2O4 coatings with an organic binder results mainly from a large electrochemically active area. Incorporation of the nickel binder between the CoFe2O4 particles causes an increase in both the conductivity and the electrochemically active area. The Tafel slopes indicate that the same rate-determining step controls the OER for all obtained coatings. Furthermore, it was shown that the CoFe2O4 electrodes exhibit no significant activity decrease after 28 h of oxygen evolution. The proposed coating preparation procedures open a new path to develop high-performance OER electrocatalysts.

Lessons from a Single Amino Acid Substitution: Anticancer and Antibacterial Properties of Two Phospholipase A2-Derived Peptides

The membrane-active nature of phospholipase A2-derived peptides makes them potential candidates for antineoplastic and antibacterial therapies. Two short 13-mer C-terminal fragments taken from snake venom Lys49-PLA2 toxins (p-AppK and p-Acl), differing by a leucine/phenylalanine substitution, were synthesized and their bioactivity was evaluated. Their capacity to interfere with the survival of Gram-positive and Gram-negative bacteria as well as with solid and liquid tumors was assessed in vitro. Toxicity to red blood cells was investigated via in silico and in vitro techniques. The mode of action was mainly studied by molecular dynamics simulations and membrane permeabilization assays. Briefly, both peptides have dual activity, i.e., they act against both bacteria, including multidrug-resistant strains and tumor cells. All tested bacteria were susceptible to both peptides, Pseudomonas aeruginosa being the most affected. RAMOS, K562, NB4, and CEM cells were the main leukemic targets of the peptides. In general, p-Acl showed more significant activity, suggesting that phenylalanine confers advantages to the antibacterial and antitumor mechanism, particularly for osteosarcoma lines (HOS and MG63). Peptide-based treatment increased the uptake of a DNA-intercalating dye by bacteria, suggesting membrane damage. Indeed, p-AppK and p-Acl did not disrupt erythrocyte membranes, in agreement with in silico predictions. The latter revealed that the peptides deform the membrane and increase its permeability by facilitating solvent penetration. This phenomenon is expected to catalyze the permeation of solutes that otherwise could not cross the hydrophobic membrane core. In conclusion, the present study highlights the role of a single amino acid substitution present in natural sequences towards the development of dual-action agents. In other words, dissecting and fine-tuning biomembrane remodeling proteins, such as snake venom phospholipase A2 isoforms, is again demonstrated as a valuable source of therapeutic peptides.