Polythiophene modified chitosan/magnetite nanocomposites for heavy metals and selective mercury removal

Multi-functional nanocomposites were prepared based on magnetite nanoparticles, chitosan nanoparticles and polythiophene for efficient and selective mercury (II) removal from its aqueous solution. The prepared materials combine several functionalities; hydroxyl, amino, sulphur and phosphate groups in addition to the magnetite property of magnetite nanoparticles. The produced nanocomposites not only show a complete removal of mercury (II) ions but also a higher selectivity was recorded in presence of other metal ions over a wider pH range.     

Iterated Virtual Screening-Assisted Antiviral and Enzyme Inhibition Assays Reveal the Discovery of Novel Promising Anti-SARS-CoV-2 with Dual Activity

Unfortunately, COVID-19 is still a threat to humankind and has a dramatic impact on human health, social life, the world economy, and food security. With the limited number of suggested therapies under clinical trials, the discovery of novel therapeutic agents is essential. Here, a previously identified anti-SARS-CoV-2 compound named Compound 13 (1,2,5-Oxadiazole-3-carboximidic acid, 4,4′-(methylenediimino) bis,bis[[(2-hydroxyphenyl)methylene]hydrazide) was subjected to an iterated virtual screening against SARS-CoV-2 M^pro using a combination of Ligand Designer and PathFinder. PathFinder, a computational reaction enumeration tool, was used for the rapid generation of enumerated structures via default reaction library. Ligand designer was employed for the computerized lead optimization and selection of the best structural modification that resulted in a favorable ligand–protein complex. The obtained compounds that showed the best binding to M^pro were re-screened against TMPRSS2, leading to the identification of 20 shared compounds. The compounds were further visually inspected, which resulted in the identification of five shared compounds M1–5 with dual binding affinity. In vitro evaluation and enzyme inhibition assay indicated that M3, an analogue of Compound 13 afforded by replacing the phenolic moiety with pyridinyl, possesses an improved antiviral activity and safety. M3 displayed in vitro antiviral activity with IC₅₀ 0.016 µM and M^pro inhibition activity with IC₅₀ 0.013 µM, 7-fold more potent than the parent Compound 13 and potent than the antivirals drugs that are currently under clinical trials. Moreover, M3 showed potent activity against human TMPRSS2 and furin enzymes with IC₅₀ 0.05, and 0.08 µM, respectively. Molecular docking, WaterMap analysis, molecular dynamics simulation, and R-group analysis confirmed the superiority of the binding fit to M3 with the target enzymes. WaterMap analysis calculated the thermodynamic properties of the hydration site in the binding pocket that significantly affects the biological activity. Loading M3 on zinc oxide nanoparticles (ZnO NPs) increased the antiviral activity of the compound 1.5-fold, while maintaining a higher safety profile. In conclusion, lead optimized discovery following an iterated virtual screening in association with molecular docking and biological evaluation revealed a novel compound named M3 with promising dual activity against SARS-CoV-2. The compound deserves further investigation for potential clinical-based studies.     

Decreased stature in gestational diabetes mellitus

Short stature has been associated with various degrees of abnormal glucose tolerance in middle-aged people, where the effects of age and metabolic control would be difficult to exclude. We chose to examine body stature in women with gestational diabetes mellitus (GDM), a prediabetic state affecting a young group of people. A sample of 2772 Greek pregnant women, referred for GDM screening was examined. After a 100-g oral glucose tolerance test, 1787 women were classified as normal (N), 300 women were found with one abnormal glucose value (OAV) and 685 women with GDM. Basal insulin resistance was calculated in 640 women by homeostasis model assessment. In addition, 51 pregnant women with pre-existing Type II (non-insulin-dependent) diabetes mellitus and 109 with pre-existing Type I (insulin-dependent) diabetes mellitus were included in the study. There was a gradual decrease in mean height (cm) as glucose intolerance became more severe: N: 161.0 +/- 6.2, OAV:160.2 +/- 6.1, GDM:158.7 +/- 6.3, Type II diabetes 158.2 +/- 7.0 (p < 0.001, analysis of variance]. Height in Type I diabetes (160.1 +/- 5.9) did not differ from the normal group. The difference in height between the normal and GDM groups remained (p < 0.001) when body weight, age, birth before or after 1960 and educational status were also taken into account. An independent correlation was also found between height and insulin resistance (n = 640) adjusted for the above mentioned variables. In conclusion, short stature appears to be associated with glucose intolerance as an independent variable, even when this intolerance is both mild and temporary. The previously unrecognised independent association of stature with basal insulin resistance merits further investigation.     

Knowledge,attitude, and behavior of students regarding 'mad cow disease'

The aim of the current study is to assess the knowledge, attitude and behavior of students enrolled at the American University of Beirut (AUB) in Lebanon, towards mad cow disease (MCD). Three hundred and fifty-six students (199 males and 157 females), ranging in age between 17 and 25 years were randomly selected from various majors and were asked to fill out a self-administered questionnaire. It was found that 99.7% of students had heard about MCD and 85.8% knew that the cow is the host for bovine spongiform encephalopathy (BSE). Seventy five percent reported that animals contract the disease through the consumption of meat and bone meal. Thirty-seven percent wrongly believed that MCD cases were reported in Lebanon and 89% were not satisfied with the measures undertaken by the Lebanese government to curb the disease. Eighty four percent were concerned about the disease and 72% stated having modified their eating habits accordingly. Moreover, students majoring in biology and other health-related majors knew significantly more about MCD compared with students majoring in non-health related majors. A surprising finding was that females were more likely to modify their eating habits than males. Hence, this study provides an insight into the knowledge, attitude, and behavior of AUB students towards MCD. A limitation of this study is that our sample is not representative of all university students in Lebanon. Future surveys should also target students enrolled in other universities in the country.     

Resistance to acid degradation,sorptivity, and setting time of geopolymer mortars

Experimental evaluations were conducted to determine the water sorptivity, setting time, and resistance to a highly acidic environment, of mortar with alkali-activated ground granulated blast furnace slag (GBS) binder and also of combinations of fly ash and GBS binders. Binders were activated using mixtures of NaOH and Na₂SiO₃ solutions. The molarity of NaOH in the mixtures ranged from 10 mol·L⁻¹ to 16 mol·L⁻¹, and the Na₂SiO₃/NaOH ratio was varied from 1.5 to 2.5. Mortar samples were produced using three binder combinations: 1) GBS as the only binder; 2) blended binder with a slag-to-fly ash ratio of 3:1; and 3) mixed binder with 1:1 ratio of slag to fly ash. Mortar samples were mixed and cured at (22 ± 2) °C till the day of the test. The impact of activator solution alkalinity, activator ratio Na₂SiO₃/NaOH, GBS content on the rate of water absorption were evaluated. After 7, 28, and 90 d of immersion in a 10% sulfuric acid solution, the resistance of a geopolymer matrix to degradation was assessed by measuring the change in sample weight. The influence of solution alkalinity and relative fly ash content on setting times was investigated. Alkali-activated mortar with a slag-to-fly ash ratio of 3:1 had the least sorptivity compared to the two other binder combinations, at each curing age, and for mortars made with each of the NaOH alkaline activator concentrations. Mortar sorptivity decreased with age and sodium hydroxide concentrations, suggesting the production of geopolymerization products. No reduction in weight of sample occurred after immersion in the strong acid H₂SO₄ solution for three months, regardless of binder combination. This was due to the synthesis of hydration and geopolymerization products in the presence of curing water, which outweighed the degradation of the geopolymer matrix caused by sulfuric acid.     

New Bioactive Fused Triazolothiadiazoles as Bcl-2-Targeted Anticancer Agents

A series of 3-(6-substituted phenyl-[1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazol-3-yl)-1H-indoles (5a–l) were designed, synthesized and evaluated for anti-apoptotic Bcl-2-inhibitory activity. Synthesis of the target compounds was readily accomplished through a reaction of acyl hydrazide (1) with carbon disulfide in the presence of alcoholic potassium hydroxide to afford the corresponding intermediate potassium thiocarbamate salt (2), which underwent cyclization reaction in the presence of excess hydrazine hydrate to the corresponding triazole thiol (3). Further cyclisation reaction with substituted benzoyl chloride derivatives in the presence of phosphorous oxychloride afforded the final 6-phenyl-indol-3-yl [1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazole compounds (5a–l). The novel series showed selective sub-micromolar IC₅₀ growth-inhibitory activity against Bcl-2-expressing human cancer cell lines. The most potent 6-(2,4-dimethoxyphenyl) substituted analogue (5k) showed selective IC₅₀ values of 0.31–0.7 µM against Bcl-2-expressing cell lines without inhibiting the Bcl-2-negative cell line (Jurkat). ELISA binding affinity assay (interruption of Bcl-2-Bim interaction) showed potent binding affinity for (5k) with an IC₅₀ value of 0.32 µM. Moreover, it fulfils drug likeness criteria as a promising drug candidate.     

The effects of crude oil shocks on stock market shifts behaviour: A regime switching approach

In this paper we develop a two regime Markov-switching EGARCH model introduced by Henry [Henry, O., 2009. Regime switching in the relationship between equity returns and short-term interest rates. Journal of Banking and Finance 33, 405–414.] to examine the relationship between crude oil shocks and stock markets. An application to stock markets of UK, France and Japan over the sample period January 1989 to December 2007 illustrates plausible results. We detect two episodes of series behaviour one relative to low mean/high variance regime and the other to high mean/low variance regime. Furthermore, there is evidence that common recessions coincide with the low mean/high variance regime. In addition, we allow both real stock returns and probability of transitions from one regime to another to depend on the net oil price increase variable. The findings show that rises in oil price has a significant role in determining both the volatility of stock returns and the probability of transition across regimes.     

Adrenomedullin Mitigates Doxorubicin-Induced Nephrotoxicity in Rats: Role of Oxidative Stress,Inflammation, Apoptosis,and Pyroptosis

Doxorubicin (DOX) is an anticancer antibiotic which has various effects in human cancers. It is one of the commonly known causes of drug-induced nephrotoxicity, which results in acute renal injury. Adrenomedullin (ADM), a vasodilator peptide, is widely distributed in many tissues and has potent protective effects. Therefore, the current study aimed to examine the protective potential mechanisms of ADM against DOX-induced nephrotoxicity. A total of 28 male Wistar rats were randomized into four groups: control group, doxorubicin group (15 mg/kg single intraperitoneal injection of DOX), adrenomedullin + doxorubicin group (12 μg/kg/day intraperitoneal injection of ADM) 3 days prior to DOX injection and continuing for 14 days after the model was established, and adrenomedullin group. Kidney function biomarkers, oxidative stress markers, and inflammatory mediators (TNF-α, NLRP3, IL-1β, and IL-18) were assessed. The expressions of gasdermin D and ASC were assessed by real-time PCR. Furthermore, the abundances of caspase-1 (p20), Bcl-2, and Bax immunoreactivity were evaluated. ADM administration improved the biochemical parameters of DOX-induced nephrotoxicity, significantly reduced oxidative damage markers and inflammatory mediators, and suppressed both apoptosis and pyroptosis. These results were confirmed by the histopathological findings and revealed that ADM’s antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties may have prospective applications in the amelioration of DOX-induced nephrotoxicity.     

Assessment of the potential of Arabic gum as an antimicrobial and antioxidant agent in developing vegan “egg-free” mayonnaise

The main factors affecting the spoilage of mayonnaise are lipid oxidation and microbial contamination. Therefore, the investigation was carried out to estimate the antimicrobial and antioxidant properties of the aqueous extract of the Arabic gum (AG). The effect of the addition of AG powder on physical–chemical and sensory properties has been evaluated in different percentages of 25, 50, 75, and 100 into mayonnaise. At the highest concentration of AG 20 mg/ml, the DPPH result represented high antioxidant activity at 92.13%. AG had inhibitory effects on gram-negative and gram-positive bacteria, with Staphylococcus aureus and Bacillus subtilis being the most susceptible bacteria. The use of AG as an egg substitute in mayonnaise has been shown to have a great effect on physical–chemical properties. All mayonnaise samples were sensory acceptable, particularly vegan mayonnaise (100% AG) and still acceptable for consumption at 5°C for 5 months of storage. AG could be considered an additive with significant emulsifier properties, antioxidant, and antimicrobial activities. Therefore, AG is a good choice to produce new vegetarian products for consumers who are unable to eat egg-based foods.