Synthesis and Anti-Cancer Activity of New Pyrazolinyl-Indole Derivatives: Pharmacophoric Interactions and Docking Studies for Identifying New EGFR Inhibitors

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the ¹H NMR, ¹³C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells’ growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.     

The Role of Antibodies in the Treatment of SARS-CoV-2 Virus Infection,and Evaluating Their Contribution to Antibody-Dependent Enhancement of Infection

Antibodies play a crucial role in the immune response, in fighting off pathogens as well as helping create strong immunological memory. Antibody-dependent enhancement (ADE) occurs when non-neutralising antibodies recognise and bind to a pathogen, but are unable to prevent infection, and is widely known and is reported as occurring in infection caused by several viruses. This narrative review explores the ADE phenomenon, its occurrence in viral infections and evaluates its role in infection by SARS-CoV-2 virus, which causes coronavirus disease 2019 (COVID-19). As of yet, there is no clear evidence of ADE in SARS-CoV-2, though this area is still subject to further study.     

Detection of Porphyrins in Hair Using Capillary Liquid Chromatography-Mass Spectrometry

Unlike humans, some animals have evolved a physiological ability to deposit porphyrins, which are pigments produced during heme synthesis in cells, in the skin and associated integument such as hair. Given the inert nature and easiness of collection of hair, animals that present porphyrin-based pigmentation constitute unique models for porphyrin analysis in biological samples. Here we present the development of a simple, rapid, and efficient analytical method for four natural porphyrins (uroporphyrin I, coproporphyrin I, coproporphyrin III and protoporphyrin IX) in the Southern flying squirrel Glaucomys volans, a mammal with hair that fluoresces and that we suspected has porphyrin-based pigmentation. The method is based on capillary liquid chromatography-mass spectrometry (CLC-MS), after an extraction procedure with formic acid and acetonitrile. The resulting limits of detection (LOD) and quantification (LOQ) were 0.006–0.199 and 0.021–0.665 µg mL⁻¹, respectively. This approach enabled us to quantify porphyrins in flying squirrel hairs at concentrations of 3.6–353.2 µg g⁻¹ with 86.4–98.6% extraction yields. This method provides higher simplicity, precision, selectivity, and sensitivity than other methods used to date, presenting the potential to become the standard technique for porphyrin analysis.     

A novel energy‐aware routing mechanism for SDN‐enabled WSAN

Energy consumption is one of the most important design constraints when building a wireless sensor and actuator network since each device in the network has a limited battery capacity, and prolonging the lifetime of the network depends on saving energy. Overcoming this challenge requires a smart and reconfigurable network energy management strategy. The Software‐Defined Networking (SDN) paradigm aims at building a flexible and dynamic network structure, especially in wireless sensor networks. In this study, we propose an SDN‐enabled wireless sensor and actuator network architecture that has a new routing discovery mechanism. To build a flexible and energy‐efficient network structure, a new routing decision approach that uses a fuzzy‐based Dijkstra's algorithm is developed in the study. The proposed architecture can change the existing path during data transmission, which is the key property of our model and is achieved through the adoption of the SDN approach. All the components and algorithms of the proposed system are modeled and simulated using the Riverbed Modeler software for more realistic performance evaluation. The results indicate that the proposed SDN‐enabled structure with fuzzy‐based Dijkstra's algorithm outperforms the one using the regular Dijkstra's and the ZigBee‐based counterpart, in terms of the energy consumption ratio, and the proposed architecture can provide an effective cluster routing while prolonging the network lifetime.     

Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro,In Vivo and Clinical Studies

Chemoradiation-induced mucositis is a debilitating condition of the gastrointestinal tract eventuating from antineoplastic treatment. It is believed to occur primarily due to oxidative stress mechanisms, which generate Reactive Oxygen Species (ROS). The aim of this scoping review was to assess the role of oxidative stress in the development of Oral Mucositis (OM). Studies from the literature, published in MEDLINE and SCOPUS, that evaluated the oxidative stress pathways or antioxidant interventions for OM, were retrieved to elucidate the current understanding of their relationship. Studies failing inclusion criteria were excluded, and those suitable underwent data extraction, using a predefined data extraction table. Eighty-nine articles fulfilled criteria, and these were sub-stratified into models of study (in vitro, in vivo, or clinical) for evaluation. Thirty-five clinical studies evaluated antioxidant interventions on OM’s severity, duration, and pain, amongst other attributes. A number of clinical studies sought to elucidate the protective or therapeutic effects of compounds that had been pre-determined to have antioxidant properties, without directly assessing oxidative stress parameters (these were deemed “indirect evidence”). Forty-seven in vivo studies assessed the capacity of various compounds to prevent OM. Findings were mostly consistent, reporting reduced OM severity associated with a reduction in ROS, malondialdehyde (MDA), myeloperoxidase (MPO), but higher glutathione (GSH) and superoxide dismutase (SOD) activity or expression. Twenty-one in vitro studies assessed potential OM therapeutic interventions. The majority demonstrated successful a reduction in ROS, and in select studies, secondary molecules were assessed to identify the mechanism. In summary, this review highlighted numerous oxidative stress pathways involved in OM pathogenesis, which may inform the development of novel therapeutic targets.     

Cumulative Sum Control Charts for Monitoring Weibull‐distributed Time Between Events

The Weibull distribution can be used to effectively model many different failure mechanisms due to its inherent flexibility through the appropriate selection of a shape and a scale parameter. In this paper, we evaluate and compare the performance of three cumulative sum (CUSUM) control charts to monitor Weibull‐distributed time‐between‐event observations. The first two methods are the Weibull CUSUM chart and the exponential CUSUM (ECUSUM) chart. The latter is considered in literature to be robust to the assumption of the exponential distribution when observations have a Weibull distribution. For the third CUSUM chart included in this study, an adjustment in the design of the ECUSUM chart is used to account for the true underlying time‐between‐event distribution. This adjustment allows for the adjusted ECUSUM chart to be directly comparable to the Weibull CUSUM chart. By comparing the zero‐state average run length and average time to signal performance of the three charts, the ECUSUM chart is shown to be much less robust to departures from the exponential distribution than was previously claimed in the literature. We demonstrate the advantages of using one of the other two charts, which show surprisingly similar performance. Copyright © 2014 John Wiley & Sons, Ltd.     

Land use/cover dynamics and their effects in the Gerado catchment,northeastern Ethiopia

This paper analyses the land use/cover dynamics of land degradation through the interpretation of aerial photographs (1958 and 1980) and 2006 SPOT-5 satellite image of the Gerado catchment. Other, non-visual data were gathered from personal interview and focus group discussions conducted in 2010 and 2011 with local elders, farmers and development (agricultural extension) agents. The results identified the presence of cultivated and rural settlement land, shrubland, woodland, bare land, grassland, urban built up area and forest. Throughout the period 1958–2006, urban built-up area, forest and cultivated and rural settlement land expanded at an average rate of 6.85%, 1.85% and 0.14% per year at the expense of shrub, wood and grasslands, which declined by 0.77%, 0.21%, 0.65% per year, respectively. The land use/cover dynamics of 1958–2006 resulted in the reduction/loss of biodiversity, occurrence of high soil erosion and ramification of gullies. The triggers for these changes were population growth, land cultivation, expansion of farmland, inappropriate land management, civil war and fuel wood demand. These led to further land degradation and more food insecurity among many farming households. Land resources have to be used according to their suitability. Thus, the exposed and steep mountains of the area have to be protected from cultivation and should be re-afforested. The paper discusses other implications for management and policy formulation also.