Classification of drug molecules for oxidative stress signalling pathway

In humans, oxidative stress is involved in the development of diabetes, cancer, hypertension, Alzheimers’ disease, and heart failure. One of the mechanisms in the cellular defence against oxidative stress is the activation of the Nrf2‐antioxidant response element (ARE) signalling pathway. Computation of activity, efficacy, and potency score of ARE signalling pathway and to propose a multi‐level prediction scheme for the same is the main aim of the study as it contributes in a big amount to the improvement of oxidative stress in humans. Applying the process of knowledge discovery from data, required knowledge is gathered and then machine learning techniques are applied to propose a multi‐level scheme. The validation of the proposed scheme is done using the K‐fold cross‐validation method and an accuracy of 90% is achieved for prediction of activity score for ARE molecules which determine their power to refine oxidative stress.Inspec keywords: cancer, cellular biophysics, biochemistry, drugs, molecular biophysics, proteins, learning (artificial intelligence), medical computingOther keywords: oxidative stress, Nrf2‐antioxidant response element signalling pathway, ARE signalling pathway, diabetes, cancer, hypertension, Alzheimers’ disease, heart failure, machine learning techniques, K‐fold cross‐validation method, ARE molecules     

A High Gain and Low Flicker Noise CMOS Mixer with Low Flicker Noise Corner Frequency Using Tunable Differential Active Inductor

This paper presents the design of a high conversion gain and low flicker noise down conversion CMOS double balanced Gilbert cell mixer using \(0.18\,\upmu \hbox {m}\) CMOS technology. The high conversion gain and low flicker noise mixer is implemented by using a differential active inductor (DAI) circuit and cross-coupled current injection technique within the conventional double-balanced Gilbert cell mixer. A cross-coupled current bleeding circuit is used to inject the current to the switching stage to decrease the flicker noise. Instead of spiral inductor, a DAI with high tunability of the inductor and quality factor is used to tune out the parasitic capacitance effect and decrease the leakage current that has a harmonic component and produce the flicker noise. By tuning the DAI, the flicker noise corner frequency is reduced to 150 Hz. The proposed circuit is simulated with Cadence Spectra and the simulation results shows the NF of 11.2 dB, conversion gain of 23.7 dB and IIP3 of \(-6\)  dB for an RF frequency of 2.4 GHz. The excellent LO-RF, LO-IF, RF-LO and RF-IF isolations of \(-60, -110, -52\) and \(-64\)  dB are achieved respectively. The total power consumption is 10.5 mW from a 1.8 V DC power supply.     

Dental Composites with Magnesium Doped Zinc Oxide Nanoparticles Prevent Secondary Caries in the Alloxan-Induced Diabetic Model

Antibacterial restorative materials against caries-causing bacteria are highly preferred among high-risk patients, such as the elderly, and patients with metabolic diseases such as diabetes. This study aimed to enhance the antibacterial potential of resin composite with Magnesium-doped Zinc oxide (Mg-doped ZnO) nanoparticles (NPs) and to look for their effectiveness in the alloxan-induced diabetic model. Hexagonal Mg-doped ZnO NPs (22.3 nm diameter) were synthesized by co-precipitation method and characterized through ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) analysis. The Mg-doped ZnO NPs (1, 2.5 and 5% w/w) were then evaluated for antibacterial activity using a closed system in vitro biofilm model. Significant enhancement in the antibacterial properties was observed in composites with 1% Mg-doped ZnO compared to composites with bare ZnO reinforced NPs (Streptococcus mutans, p = 0.0005; Enterococcus faecalis, p = 0.0074, Saliva microcosm, p < 0.0001; Diabetic Saliva microcosm, p < 0.0001). At 1–2.5% Mg-doped ZnO NPs concentration, compressive strength and biocompatibility of composites were not affected. The pH buffering effect was also achieved at these concentrations, hence not allowing optimal conditions for the anaerobic bacteria to grow. Furthermore, composites with Mg-doped ZnO prevented secondary caries formation in the secondary caries model of alloxan-induced diabetes. Therefore, Mg-doped ZnO NPs are highly recommended as an antibacterial agent for resin composites to avoid biofilm and subsequent secondary caries formation in high-risk patients.     

tert-Butyl Nitrite Promoted Visible-Light-Induced Steric-Hindrance-Regulated Concurrent Cross-Coupling and Regioselective Nitration of 3-Alkylidene-2-oxindoles

A tert-butyl nitrite (TBN) promoted visible-light-induced one-pot C−N cross coupling reaction of 3-alkylidene-2-oxindoles with benzene-1,2-diamine was explored. Simultaneously, the indoline motif of 3-alkylidene-2-oxindoles as well as 3-ylidene oxindoles are regioselectively nitrated at the C-6 position by in-situ formed NO₂ radical. (E)-3-(2-(aryl)-2-oxoethylidene)oxindole and (E)-3-ylidene oxindole produce distinct nitrated diastereomeric coupling products, a phenomenon influenced by the steric bulk of the functional group. The experimental findings suggest the potential involvement of a radical pathway in this reaction.     

Quinolizidines as Novel SARS-CoV-2 Entry Inhibitors

COVID-19, caused by the highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread and become a pandemic since its outbreak in 2019. We have previously discovered that aloperine is a new privileged scaffold that can be modified to become a specific antiviral compound with markedly improved potency against different viruses, such as the influenza virus. In this study, we have identified a collection of aloperine derivatives that can inhibit the entry of SARS-CoV-2 into host cells. Compound 5 is the most potent tested aloperine derivative that inhibited the entry of SARS-CoV-2 (D614G variant) spike protein-pseudotyped virus with an IC₅₀ of 0.5 µM. The compound was also active against several other SARS-CoV-2 variants including Delta and Omicron. Results of a confocal microscopy study suggest that compound 5 inhibited the viral entry before fusion to the cell or endosomal membrane. The results are consistent with the notion that aloperine is a privileged scaffold that can be used to develop potent anti-SARS-CoV-2 entry inhibitors.     

Suggestion Mining from Opinionated Text of Big Social Media Data

Social media data are rapidly increasing and constitute a source of user opinions and tips on a wide range of products and services. The increasing availability of such big data on biased reviews and blogs creates challenges for customers and businesses in reviewing all content in their decision-making process. To overcome this challenge, extracting suggestions from opinionated text is a possible solution. In this study, the characteristics of suggestions are analyzed and a suggestion mining extraction process is presented for classifying suggestive sentences from online customers’ reviews. A classification using a word-embedding approach is used via the XGBoost classifier. The two datasets used in this experiment relate to online hotel reviews and Microsoft Windows App Studio discussion reviews. F1, precision, recall, and accuracy scores are calculated. The results demonstrated that the XGBoost classifier outperforms—with an accuracy of more than 80%. Moreover, the results revealed that suggestion keywords and phrases are the predominant features for suggestion extraction. Thus, this study contributes to knowledge and practice by comparing feature extraction classifiers and identifying XGBoost as a better suggestion mining process for identifying online reviews.     

Simultaneous protective effect of a new chelating agent and zinc, on the carbon tetrachloride induced hepatic injury in squirrels

X-ray test of the osteo-articular system of upper limbs was carried out on 1231 saweyers and 272 controls as well as 50 intellectuals. Three x-ray tests were carried out on 207 sawyers and on a control group of 95 workers, to assess the progression of osseous changes. The same types od changes were found in sawyers and control group workers; besides similar frequency in the examined parts of the upper limb was found in them. The most frequent changes are: osseous cyst, osteoporosis degenerative-deformative changes and calcar of the ulnar. The greatest amounts of changes were observed in the bones and joints of the hand and next in elbow joint and acromioclavicular joint. It was observed that amoungst the sawyers and the control group workers, the greatest amounts of changes occur after 2 years of work. Progression of osseous changes after 3-4 years of work was observed in 30,9% sawyers and 12,6% control group workers.