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Abstract Tyrosinase is a binuclear copper-containing enzyme that catalyzes the conversation of monophenols to diphenols via o-hydroxylation and then the oxidation of o-diphenols to o-quinones which is profoundly linked to eukaryotic melanin synthesis and fruits browning. The hyperpigmentation due to unusual tyrosinase activity has gained growing health concern. Plants and their metabolites are considered promising and effective sources for potent antityrosinase enzymes. Hence, searching for potent, specific tyrosinase inhibitor from different plant extracts is an alternative approach in regulating overproduction of tyrosinase. Among the tested extracts, the hydro-alcoholic extract of Moringa oleifera L. leaves displayed the potent anti-tyrosinase activity (IC50 = 98.93 µg/ml) in a dose-dependent manner using L-DOPA as substrate; however, the kojic acid showed IC50 of 88.92 µg/ml. The tyrosinase-diphenolase (TYR-Di) kinetic analysis revealed mixed inhibition type for the Ocimum basilicum L. and Artemisia annua L. extracts, while the Coriandrum sativum L. extract displayed a non-competitive type of inhibition. Interestingly, the extract of Moringa oleifera L. leaves exhibited a competitive inhibition, low inhibition constant of free enzyme ( $${\text{K}}_{\text{ii}}^{\text{app}}$$ K ii app ) value and no Pan-Assay Interfering Substances, hinting the presence of strong potent inhibitors. The major putative antityrosinase compound in the extract was resolved, and chemically identified as rutin based on various spectroscopic analyses using UV–Vis, FTIR, mass spectrometry, and 1H NMR. The in silico computational molecular docking has been performed using rutin and A. bisporus tyrosinase (PDB code: 2Y9X). The binding energy of the predicted interaction between tropolone native ligand, kojic acid, and rutin against 2Y9X was respectively − 5.28, − 4.69, and − 7.75 kcal/mol. The docking simulation results revealed the reliable binding of rutin to the amino acid residues (ASN260, HIS259, SER282) in the tyrosinase catalytic site. Based on the developed results, rutin extracted from M. oleifera L. leaves has the capability to be powerful anti-pigment agent with a potential application in cosmeceutical area. In vivo studies are required to unravel the safety and efficiency of rutin as antityrosinase compound.

Abstract Background The infamous multidrug-resistant (MDR) bacterium Acinetobacter baumannii is becoming a nightmare in intensive care units across the globe. Since there are now very few effective antimicrobial agents, it is necessary to explore unconventional resources for novel antimicrobials. This study investigated the potential antimicrobial activity of Origanum majorana L. against A. baumannii employing multiple approaches including antimicrobial susceptibility, fractionation, ultra-performance liquid chromatography–high-resolution mass spectrometry (UPLC-HRMS) dereplication, and in silico analysis for target/ligand identification. Results On the extremely pathogenic MDR strain A. baumannii AB5075, O. majorana L. has shown a significant growth inhibitory effect (MIC = 0.675 mg/mL). The polar 50% methanol fraction was the most active (MIC = 0.5 mg/mL). The UPLC-HRMS dereplication of the bioactive fraction detected 29 metabolites belonging to different chemical classes. Justicidin B, one of the identified metabolites, was projected by preliminary in silico analysis to be the most highly scoring metabolite for binding with molecular targets in A. baumannii with a Fit score = 8.56 for enoyl-ACP reductase (FabI) (PDB ID: 6AHE), suggesting it to be its potential target. Additionally, docking, molecular dynamics simulation, and bioinformatics analysis suggested that this interaction is similar to a well-known FabI inhibitor. The amino acids involved in the interaction are conserved among different MDR A. baumannii strains and the effectiveness could extend to Gram-negative pathogens within the ESKAPE group. Conclusions Origanum majorana L. extract exhibits antimicrobial activity against A. baumannii using one or more metabolites in its 50% methanol fraction. The characterized active metabolite is hypothesized to be justicidin B which inhibits the growth of A. baumannii AB5075 via targeting its fatty acid synthesis.

IntroductionToxic heavy metal pollution has been considered a major ecosystem pollution source. Unceasing or rare performance of Pb2+ to the surrounding environment causes damage to the kidney, nervous, and liver systems. Microbial remediation has acquired prominence in recent decades due to its high efficiency, environment-friendliness, and cost-effectiveness.MethodsThe lead biosorption by Bacillus subtilis was optimized by two successive paradigms, namely, a definitive screening design (DSD) and an artificial neural network (ANN), to maximize the sorption process.ResultsFive physicochemical variables showed a significant influence (p < 0.05) on the Pb2+ biosorption with optimal levels of pH 6.1, temperature 30°C, glucose 1.5%, yeast extract 1.7%, and MgSO4.7H2O 0.2, resulting in a 96.12% removal rate. The Pb2+ biosorption mechanism using B. subtilis biomass was investigated by performing several analyses before and after Pb2+ biosorption. The maximum Pb2+ biosorption capacity of B. subtilis was 61.8 mg/g at a 0.3 g biosorbent dose, pH 6.0, temperature 30°C, and contact time 60 min. Langmuir’s isotherm and pseudo-second-order model with R2 of 0.991 and 0.999 were suitable for the biosorption data, predicting a monolayer adsorption and chemisorption mechanism, respectively.DiscussionThe outcome of the present research seems to be a first attempt to apply intelligence paradigms in the optimization of low-cost Pb2+ biosorption using B. subtilis biomass, justifying their promising application for enhancing the removal efficiency of heavy metal ions using biosorbents from contaminated aqueous systems.

Background: The COVID-19 pandemic has been linked to dyslipidemia in patients. Objective: To investigate the alterations in serum low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, very low-density lipoprotein (VLDL), total cholesterol (TC), and triglycerides (TG) levels in individuals with COVID-19 infection. Cases and Methods: This study was conducted at Jabra Hospital, Khartoum state, Sudan, from February to September 2021. It was an analytical, controlled hospital-based study that involved a total of 136 subjects. Of these, 68 were Sudanese patients who had contracted COVID-19, while the other 68 were healthy individuals who served as the control group. Data was collected through a questionnaire, and the serum lipid profile was estimated using spectrophotometric methods through an enzymatic process. The data was analyzed using SPSS (V25). Results: The study found that patients with COVID-19 had significantly lower levels of serum LDL, VLDL, TC, and TG compared to the control group. The p-values for these differences were 0.001, 0.002, 0.000, and 0.001, respectively. There was no significant difference in serum HDL and BMI between the two groups. In the case group, serum lipid profiles (excluding HDL) were significantly higher in overweight individuals compared to those with normal weight. The p-values for these differences were 0.001, 0.002, 0.001, 0.001, and 0.001, respectively. However, there was no significant difference in serum HDL levels between the two weight groups. Interestingly, the serum lipid profile was significantly higher in overweight controls compared to the cases. The p-values for these differences were 0.001, 0.041, 0.024, 0.001, and 0.001, respectively. Lastly, the study found that the serum lipid profile was significantly lower among severe COVID-19 patients compared to the control group with a p-value of ≤0.001. In particular, serum LDL and TC were significantly lower in patients than controls, with p-values of ≤0.001 and 0.003, respectively. On the other hand, serum TG was significantly higher in cases than controls with a p-value of ≤ 0.001. Serum VLDL and HDL levels were not significantly different between the two groups. Conclusion: Research has suggested that individuals who have contracted COVID-19 have shown a decrese in lipid profile values compared to those who have not been affected by the virus.

A new series of nicotinonitrile derivatives 2–7 was designed and synthesized from the starting material (E)-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (1) to assess their molluscicidal activity. The newly synthesized nicotinonitrile compounds 2–7 were characterized based on FTIR, 1H-NMR, and 13C-APT NMR spectra as well as elemental microanalyses. The target compounds 2–7 were screened for their toxicity effect against M. cartusiana land snails and were compared to Acetamiprid as a reference compound. The results demonstrated that the nicotinonitrile-2-thiolate salts 4a and 4b had good mortality compared with that of Acetamiprid. The results of the in vivo effect of the prepared nicotinonitrile molecules 2, 4a, and 4b on biochemical parameters, including AChE, ALT, AST, and TSP, indicated a reduction in the level of AChE and TSP as well as an increase in the concentration of transaminases (ALT and AST). A histopathological study of the digestive gland sections of the M. cartusiana land snails was carried out. The nicotinonitrile-2-thiolate salts 4a,b showed vacuolization, causing the digestive gland to lose its function. It could be concluded that the water-soluble nicotinonitrile-2-thiolate salts 4a,b could be adequate molluscicidal molecules against M. cartusiana land snails.

Green nanotechnology has attracted attention worldwide, especially in treating cancer and drug-resistant section 6 microbes. This work aims to investigate the anticancer activity of green silver nanoparticles synthesized by Spirulina platensis phycocyanin (SPAgNPs) on two cancer cell lines: Lung cancer cell line (A-549) and breast cancer cell line (MCF-7), compared to the normal human lung cell line (A138). We also aimed to investigate the bactericidal activity against Staphylococcus aureus ATCC29737, Bacillus cereus ATCC11778, Escherichia coli ATCC8379, and Klebsiella pneumonia, as well as the fungicidal activity against Candida albicans (ATCC6019) and Aspergillus niger. The obtained SPAgNPs were spherical and crystalline with a size of 30 nm and a net charge of −26.32 mV. Furthermore, they were surrounded by active groups responsible for stability. The SPAgNPs scavenged 85% of the DPPH radical with a relative increase of approximately 30% over the extract. The proliferation of cancer cells using the MTT assay clarified that both cancer cells (A-549 and MCF-7) are regularly inhibited as they grow on different concentrations of SPAgNPs. The maximum inhibitory effect of SPAgNPs (50 ppm) reached 90.99 and 89.51% against A-549 and MCF7, respectively. Regarding antimicrobial activity, no inhibition zones occurred in bacterial or fungal strains at low concentrations of SPAgNPs and the aqueous Spirulina platensis extract. However, at high concentrations, inhibition zones, especially SPAgNPs, were more potent for all tested microorganisms than their positive controls, with particular reference to Staphylococcus aureus, since the inhibition zones were 3.2, 3.8, and 4.3 mm, and Bacillus cereus was 2.37 mm when compared to tetracycline (2.33 mm). SPAgNPs have more potent antifungal activity, especially against Aspergillus niger, compared to their positive controls. We concluded that SPAgNPs are powerful agents against oxidative stress and microbial infection.

Background: Sidra Medicine is the first dedicated Children and Maternity hospital in the State of Qatar. This paper describes the preparations for and results of activating quaternary neonatal surgical services in a brand new, "greenfield" hospital. We believe that these are the first published national results of neonatal general surgical services from the Gulf region. Methods: A review of surgical babies below four weeks corrected age from 1st of April 2018 – 31st of March 2020 was undertaken. Patient demographics, primary diagnosis, surgical procedures, 30-day postoperative mortality, overall mortality, and cause of death were recorded. Results: One hundred and sixty-nine babies (169) were identified (44.4% term and 55.6% preterm). Major surgery included laparotomy (76), congenital diaphragmatic hernia repair (20), surgery for anorectal malformations (25), and esophageal atresia (13). One set of conjoined twins were also separated successfully. Fourteen babies died, resulting in overall mortality of 8.3 %. Excluding babies who died of life-limiting conditions, two babies died within 30 days of surgery, resulting in 30 days postoperative mortality rate of 1.2 %. Conclusions: The neonatal surgical mortality rate is comparable with those from top international centers. This low rate could be attributed to the high level of expertise preceded by months of preparations.

Pathogenic CUG and CCUG RNA repeats have been associated with myotonic dystrophy type 1 and 2 (DM1 and DM2), respectively. Identifying small molecules that can bind these RNA repeats is of great significance to develop potential therapeutics to treat these neurodegenerative diseases. Some studies have shown that aminoglycosides and their derivatives could work as potential lead compounds targeting these RNA repeats. In this work, sisomicin, previously known to bind HIV-1 TAR, is investigated as a possible ligand for CUG RNA repeats. We designed a novel fluorescence-labeled RNA sequence of r(CUG)10 to mimic cellular RNA repeats and improve the detecting sensitivity. The interaction of sisomicin with CUG RNA repeats is characterized by the change of fluorescent signal, which is initially minimized by covalently incorporating the fluorescein into the RNA bases and later increased upon ligand binding. The results show that sisomicin can bind and stabilize the folded RNA structure. We demonstrate that this new fluorescence-based binding characterization assay is consistent with the classic UV Tm technique, indicating its feasibility for high-throughput screening of ligand-RNA binding interactions and wide applications to measure the thermodynamic parameters in addition to binding constants and kinetics when probing such interactions.

Exosomes (EXOs) were given attention as an extracellular vesicle (EV) with a pivotal pathophysiological role in the development of certain neurodegenerative disorders (NDD), such as Parkinson’s and Alzheimer’s disease (AD). EXOs have shown the potential to carry pathological and therapeutic cargo; thus, researchers have harnessed EXOs in drug delivery applications. EXOs have shown low immunogenicity as natural drug delivery vehicles, thus ensuring efficient drug delivery without causing significant adverse reactions. Recently, EXOs provided potential drug delivery opportunities in AD and promising future clinical applications with the diagnosis of NDD and were studied for their usefulness in disease detection and prediction prior to the emergence of symptoms. In the future, the microfluidics technique will play an essential role in isolating and detecting EXOs to diagnose AD before the development of advanced symptoms. This review is not reiterative literature but will discuss why EXOs have strong potential in treating AD and how they can be used as a tool to predict and diagnose this disorder.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2’s spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein’s RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.

Pediatric germ cell tumors (GCT) rarely occur in the head and neck region and they are rarely associated with congenital anomalies. A 17 month old girl presented with a history of cough and change in voice for one month. Her chest x-ray and cross sectional imaging was suggestive of a mediastinal mass, right diaphragmatic hernia, and rib abnormality. Serologic and biomarkers were all negative for tumors. Surgical resection occurred with clear margins revealing a mass arising from the left hypopharnx via a pedunculated stalk. Histopathology was consistent with a mature teratoma including significant amounts of parathyroid tissue. She remains tumor free at 18 months follow up. To the best of our knowledge our patient is the third case in which a diaphragmatic hernia was reported in association with hypopharyngeal teratoma and our patient is the first to survive; this provides an opportunity to counsel families when this association is encountered.

Background: Inguinal hernia repair remains one of the most common operations performed by pediatric surgeons. We described a new surgical approach for treating bilateral inguinal hernias in girls through a small single transverse supra-pubic incision. Materials and Methods: A new approach was performed on female children 12-years-old and younger with bilateral inguinal hernias between January 2005 and April 2012. Technique: A single transverse suprapubic incision (1-1.5 cm) was made. Using sharp and blunt dissection bilateral hernias were exposed and repaired using a standard high ligation. Results: Ninety-nine girls with a preoperative clinical diagnosis of bilateral inguinal hernia were included. Median age was 2 years (range: 1 month to 12 years). All patients underwent general anesthesia. Median operative time was 12 minutes (range 5-22). There were no intra-operative complications or misdiagnosis. Two patients had bilateral sliding hernias and the remainder had indirect hernias. Post-operatively two patients developed non-expanding small hematomas, both treated non-operatively without sequelae. There were zero hernia recurrence and median follow-up was 5 years (range: 1-8 years) on 99% of patients. Conclusion: We described a new, safe, simple, and rapid approach for bilateral inguinal hernia repair in female pediatric population. A single transverse suprapubic skin incision was adequate for exposing both inguinal regions with excellent postoperative results.

To date, absent inferior mesenteric vein (IMV) has not been reported in the literature as a cause of or being associated with lower gastrointestinal (GI) bleeding. We describe a case of 13 year-old girl who presented with hematochezia and was subsequently found to have widespread colonic varices involving the ascending, transverse and proximal descending colon. The upper GI tract, small bowel, and rectum were not involved. Delayed venous phase of mesenteric angiography revealed an absent inferior mesenteric vein. The patient underwent laparoscopic extended right hemicolectomy with ileosigmoid anastomosis. No bleeding from recurrent varices occurred during a 1-year period of follow up. We conclude that extended right hemicolectomy is a potential curative surgical option in patients presenting with lower GI bleeding from colonic varices caused by absent IMV. Upper GI and small intestinal involvement should be excluded to prevent future bleeding from missed varices these sites.

This paper presents the results of an experimental program carried out to investigate the effects of Basalt Fibre Reinforced Polymers (BFRP) on some fundamental mechanical properties of concrete. Basalt fibres are formed by heating crushed basalt rocks and funnelling the molten basalt through a spinneret to form basalt filaments. This type of fibres have not been widely used till recently. Two commercially available chopped basalt fibres products with different aspect ratios were investigated, which are dry basalt (GeoTech Fibre) and basalt pre-soaked in an epoxy resin (GeoTech Matrix) .The experimental work included compression tests on 96 cylinders made of multiple batches of concrete with varying amounts of basalt fibre additives of the two mentioned types, along with control batches containing no fibres. Furthermore, flexural tests on 24 prisms were carries out to measure the modulus of rupture, in addition to 30 prisms for average residual strength test. Results of the research indicated that use of basalt fibres has insignificant effects on compressive strength of plain concrete, where the increase in strength did not exceed about 5%. On the other hand, results suggest that the use of basalt fibres may increase the compressive strength of concrete containing fly as up top 40%. The rupture strength was increased also by 8% to 28% depending on mix and fibre types and contents. Finally, there was no clear correlation between the average residual strength and ratios of basalt fibres mixed with the different concrete batches.

Introduction: Toxic heavy metal pollution has been considered a major ecosystem pollution source. Unceasing or rare performance of Pb2+ to the surrounding environment causes damage to the kidney, nervous, and liver systems. Microbial remediation has acquired prominence in recent decades due to its high efficiency, environment-friendliness, and cost-effectiveness. Methods: The lead biosorption by Bacillus subtilis was optimized by two successive paradigms, namely, a definitive screening design (DSD) and an artificial neural network (ANN), to maximize the sorption process. Results: Five physicochemical variables showed a significant influence (p < 0.05) on the Pb2+ biosorption with optimal levels of pH 6.1, temperature 30°C, glucose 1.5%, yeast extract 1.7%, and MgSO4.7H2O 0.2, resulting in a 96.12% removal rate. The Pb2+ biosorption mechanism using B. subtilis biomass was investigated by performing several analyses before and after Pb2+ biosorption. The maximum Pb2+ biosorption capacity of B. subtilis was 61.8 mg/g at a 0.3 g biosorbent dose, pH 6.0, temperature 30°C, and contact time 60 min. Langmuir's isotherm and pseudo-second-order model with R² of 0.991 and 0.999 were suitable for the biosorption data, predicting a monolayer adsorption and chemisorption mechanism, respectively. Discussion: The outcome of the present research seems to be a first attempt to apply intelligence paradigms in the optimization of low-cost Pb2+ biosorption using B. subtilis biomass, justifying their promising application for enhancing the removal efficiency of heavy metal ions using biosorbents from contaminated aqueous systems. [ABSTRACT FROM AUTHOR]