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Misgana Ayele Hussien, Eyerusalem Berhanemeskel Haile, Bezawit Negash Demisse Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, EthiopiaCorrespondence: Bezawit Negash Demisse Email bezawit.negash@aau.edu.etPurpose: To assess the burden of unavailable drugs cost to patients admitted to TikurAnbessa Specialized Hospital’s internal medicine ward. Costs of medications obtained inside and outside the pharmacy and other burdens associated with drugs’ unavailability are also estimated and explored.Patient and Methods: A facility-based cross-sectional study design was conducted from November 9 to November 23, 2020. Quantitative data on medication costs were collected from patients admitted to TikurAnbessa Specialized Hospital internal medicine ward B8. Qualitative information was collected from patients, caregivers, and health care professionals through interviews to assess the burdens of unavailability of pharmaceuticals on patients and the health care system.Results: A total of 32 patients were enrolled in the study. Participants’ age ranged from 14 to 92. Eighteen (56.25%) paid in cash for medications bought within the hospital pharmacy, while the remaining 14 (43.75%) were treated for free. A total of 68 medicines were prescribed during the study period. Of this, 33 (48.53%) medicines were not available in the hospital pharmacy. The total costs of patients were 78.07$ and 1530.84$ when purchased from inside and outside the hospital pharmacy, respectively. The average price of medications per patient ranged from 0.025 to 8.41$ inside the hospital pharmacy, where the average cost per patient outside the hospital pharmacy ran from 0.128 to 54.67$. For the qualitative part, four patients and/or caregivers and five health care professionals were interviewed, and three key themes emerged from the thematic analysis: (i) awareness of the availability of medication, (ii) management of the burden of stock out, and (iii) impact of the stock out.Conclusion: The study came up with a result that the hospital pharmacy has high unavailability of medication. Patients complain about unwanted and unreasonably expenditure to purchase pharmaceuticals from outside pharmacies and associated delayed treatment.Keywords: burden, unavailability, hospital pharmacy

There are elevations in the number of stray dogs in different governorates in Iraq. Moreover, the number of people who are interested in keeping dog for life purpose has also risen. Every year, there are a number of populations contacted to animal bites throughout the country. Wounds due to dog bites are popular in different human ages, but are more common in children. A high rate of these dog bites affect different body locations, however, upper extremities are more common site. There is scarce information describing dog bites in Al Muthanna governorate, in addition to describe its healing process. Therefore, this study intends to report the prevalence of dog bites in Al Muthanna governorate and to describe the clinical healing process of pet dog bites in their owner arm. Materials and methods The authors retrospectively reviewed the records of dog bites who seeked emergency department at Al Muthanns hospital in Samawah city from January 2016 to November 2016 (totally 11 months). The data were analyzed and percentages of prevalence were reported. Results During the study period, there were 176 people’s emergency department visits for dog bites. Among the 176 person with dog bites, there were 41female and 135 male with percentages of 23.295% and 76.704% respectively. Moreover, the incidence of dog bites was varied between the victims age group, there were 0 (0%), 5(3% ), 57 (32%), 88 (50% ) and 26 (15%) for less than one year, 1-4 years, 5-14 years, 15-45 years and more than 45 years respectively. The total population of Al Muthanna governorate was 775 X 1000 according to total estimation of Iraq (April 2009 IMF estimate). Accordingly, the total incidence rate of dog bites in Al Muthanna governorate/ 100.000 people was 22.709 % for the total 6 population. One patient revealed clinical signs of rabies with percentage of incidence 0.568% for the total dog bites. Moreover, the percentage of rabies for total population for Al Muthanna governorate was 0.129/ 100.000. The time and healing process of dog bites extended for 3 weeks with formation of scar centrally depressed area. Conclusions In conclusion, for the authors’ knowledge this is the first study that approved the incidence of dog bites in Al Muthanna governorate. The higher incidence percentages of dog bites occur between the patients of age group 15-45 year and followed by 5-14 years. Moreover, the incidence rate of dog bites was higher in male than female. The study approved the incidence of rabies in one case between the total dog bites. The Authors recommended another future retrospective study that reviewed more years to determine the actual situation of the dog bites that act as a serious health problem in Al Muthanna as well as in another Iraqi governorates.

There are elevations in the number of stray dogs in different governorates in Iraq. Moreover, the number of people who are interested in keeping dog for life purpose has also risen. Every year, there are a number of populations contacted to animal bites throughout the country. Wounds due to dog bites are popular in different human ages, but are more common in children. A high rate of these dog bites affect different body locations, however, upper extremities are more common site. There is scarce information describing dog bites in Al Muthanna governorate, in addition to describe its healing process. Therefore, this study intends to report the incidence of dog bites in Al Muthanna governorate and to describe the clinical healing process of pet dog bites in their owner arm. The authors retrospectively reviewed the records of dog bites who seeked emergency department at Al Muthanns hospital in Samawah city from January 2016 to November 2016 (totally 11 months). During the study period, there were 176 people’s emergency department visits for dog bites. Among the 176 person with dog bites, there were 41female and 135 male with percentages of 23.295% and 76.704% respectively. Moreover, the incidence of dog bites was varied between the victims age group, there were 0 (0%), 5(3% ), 57 (32%), 88 (50% ) and 26 (15%) for less than one year, 1-4 years, 5-14 years, 15-45 years and more than 45 years respectively. The total population of Al Muthanna governorate was 775 X 1000 according to total estimation of Iraq (April 2009 IMF estimate). Accordingly, the total incidence rate of dog bites in Al Muthanna governorate/ 100.000 people was 22.709 % for the total population. One patient revealed clinical signs of rabies with percentage of incidence 0.568% for the total dog bites. Moreover, the percentage of rabies for total population for Al Muthanna governorate was 0.129/ 100.000. The time and healing process of dog bites extended for 3 weeks and left scar centrally depressed area. In conclusion, for the author’s knowledge this is the first study that approved the incidence of dog bites in Al Muthanna governorate. The higher incidence percentages of dog bites occur between the patients of age group 15-45 year and followed by 5-14 years. Moreover, the incidence rate of dog bites was higher in male than female. The study approved the incidence of rabies in one case between the total dog bites. The Authors recommended another future retrospective study that reviewed more years to determine the actual situation of the dog bites that act as a serious health problem in Al Muthanna as well as in another Iraqi governorates.

Use of Recycled Coarse Aggregate (RCA) in concrete can be described in terms of environmental protection and economy. This paper deals with the mechanical properties of concrete compressive strength, splitting tensile strength, modulus of elasticity, and modulus of rupture. Three kinds of concrete mixtures were tested, concrete made with Natural Coarse Aggregate (NCA) as a control concrete and two types of concrete made with recycled coarse aggregate (50% and 100% replacement level of coarse recycled aggregate). These kinds of concrete were made with different targets of compressive strength of concrete f ’c (35MPa) and (70 MPa). Fifty specimens were tested of the fresh and hardened properties of concrete. The waste concrete from laboratory test cubes was crushed to produce the Recycled Coarse Aggregate used in recycled concrete. A comparative between the experimental results of the properties for fresh and hardened concrete is presented in the paper. Recycled aggregate concrete (RCA) had a satisfactory performance despite the replacement ratios. It was found using the size of Recycled Coarse Aggregate (RCA) of (5-14) mm has quite similar in performance with the same size of Natural Coarse Aggregate (NCA), it is necessary to use high quality of recycled concrete (with low levels of impurities). Recycled aggregate as an alternative to natural aggregates -seems quite successful.

Background: One method for treating adolescent idiopathic scoliosis (AIS), which is characterized by abnormal spinal alignment in the coronal, sagittal, and rotational planes, is surgical correction. The two surgical techniques most typically used to correct spine alignment are simple rod derotation (SRD) and direct vertebral derotation (DVR)., Aim: The study's goal was to assess the effectiveness of two treatment methods for adolescent idiopathic scoliosis: simple rod derotation and direct vertebral rotation., Subjects and Methods: A randomized controlled research involving 36 adolescents with idiopathic scoliosis was done. Patients were randomly split into one of two groups: 18 patients in group A had DVR treatment, while 18 patients in group B received SRD with a 2-year follow-up., Results: Apical Vertebral Rotation measured from CT scans in DVR group was 24.4° ± 8.38° preoperatively and it decreased significantly postoperatively to 14.4° ± 4.61° with (42.22%) correction rate, while in SRD group, it was 25.03° ± 7.99° preoperatively and it also decreased significantly postoperatively to a mean value of 21.41° ± 7.01° with (14.65%) correction rate. There were statistically significant differences between both groups post-operative (P < 0.001)., Conclusion: The apical vertebral rotation was greatly enhanced in both procedures, with direct vertebral rotation being better. Both Simple rod derotation and direct vertebral rotation reduce the rib hump, although the improvement is much greater with direct vertebral rotation., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Environmental measures have drawn more attention recently as a means of identifying cost-effective, safe, and green approaches in analytical methods. As a result, white and green analytical chemistry was developed. Greenness, whiteness, and chemical risks are all measured under the general expression "environmental measurements." For the first time, the greenness, whiteness, and chemical risk-measuring programs are presented along with their histories, concepts, advantages, and disadvantages. The six scales that were published between 2020 and 2023, including the Analytical Greenness Calculator (AGREE), the Analytical Greenness Metric for Sample Preparation (AGREEprep), the Complementary Green Analytical Procedure Index (ComplexGAPI), Red-Green-Blue (RGB12), blue applicability grade index (BAGI), and the Chloroform-oriented Toxicity Estimation (ChlorTox) scales are discussed. Also, the applications of several analytical methods have been compared. Lastly, patterns for the future were suggested. We hope this review is helpful for analysts to stay up-to-date with recent greenness, whiteness, and chemical risk scales. Additionally, the most appropriate procedure has been chosen, applied, and compared easily.

RUBCN (also known as Rubicon) was originally identified as a negative regulator of autophagy, a process by which cells degrade and recycle damaged components or organelles and that requires the activity of the class III PI3K VPS34 and the mTORC1 protein complex. Here, we characterized the role of a shorter isoform, RUBCN 100 , as an autophagy-promoting factor in B cells. RUBCN 100 was translated from alternative translation initiation sites and lacked the RUN domain of the longer, previously characterized RUBCN 130 isoform. Specific deficiency of RUBCN 130 in B cells enhanced autophagy, which promoted memory B cell generation. In contrast to RUBCN 130 , which is localized in late endosomes and lysosomes and suppresses the enzymatic activity of VPS34, an effect thought to mediated by its RUN domain, RUBCN 100 was preferentially located in early endosomes and enhanced VPS34 activity, presumably because of the absence of the RUN domain. Furthermore, RUBCN 100 , but not RUBCN 130 , enhanced autophagy and suppressed mTORC1 activation. Our findings reveal that the opposing roles of two RUBCN isoforms are critical for autophagy regulation and memory B cell differentiation.

This research sought to synthesize a new set of heteroaromatic thiazole-based polyurea derivatives with sulfur links in the polymers' main chains, which were denoted by the acronyms PU 1-5 . Using pyridine as a solvent, a diphenylsulfide-based aminothiazole monomer (M2) was polymerized via solution polycondensation with varied aromatic, aliphatic, and cyclic diisocyanates. Typical characterization methods were used to confirm the structures of the premonomer, monomer, and fully generated polymers. The XRD results revealed that aromatic-based polymers had higher crystallinity than aliphatic and cyclic derivatives. SEM was used to visualize the surfaces of PU 1 , PU 4 , and PU 5 , revealing spongy and porous shapes, shapes resembling wooden planks and sticks, and shapes resembling coral reefs with floral shapes at various magnifications. The polymers demonstrated thermal stability. The numerical results for PDTmax are listed in the following order, ranked from lowest to highest: PU 1 < PU 2 < PU 3 < PU 5 < PU 4 . The FDT values for the aliphatic-based derivatives (PU 4 and PU 5 ) were lower than those for the aromatic-based ones (616, 655, and 665 °C). PU 3 showed the greatest inhibitory impact against the bacteria and fungi under investigation. In addition, PU 4 and PU 5 demonstrated antifungal activities that, in contrast with the other products, were on the lower end of the spectrum. Furthermore, the intended polymers were also tested for the presence of the proteins 1KNZ, 1JIJ, and 1IYL, which are frequently utilized as model organisms for E. coli (Gram-negative bacteria), S. aureus (Gram-positive bacteria), and C. albicans (fungal pathogens). This study's findings are consistent with the outcomes of the subjective screening.

Medicinal plants provide a wide range of active compounds that can be exploited to create novel medicines with minimal side effects. The current study aimed to identify the anticancer properties of Juniperus procera ( J. procera ) leaves. Here, we demonstrate that J. procera leaves' methanolic extract suppresses cancer cells in colon (HCT 116 ), liver (HepG2), breast (MCF-7), and erythroid (JK-1) cell lines. By applying GC/MS, we were able to determine the components of the J. procera extract that might contribute to cytotoxicity. Molecular docking modules were created that used active components against cyclin-dependent kinase 5 (Cdk5) in colon cancer, aromatase cytochrome P450 in the breast cancer receptor protein, the -N terminal domain in the erythroid cancer receptor of the erythroid spectrin, and topoisomerase in liver cancer. The results demonstrate that, out of the 12 bioactive compounds generated by GC/MS analysis, the active ingredient 2-imino-6-nitro-2 H -1-benzopyran-3-carbothiamide proved to be the best-docked chemical with the chosen proteins impacted by DNA conformational changes, cell membrane integrity, and proliferation in molecular docking studies. Notably, we uncovered the capacity of J. procera to induce apoptosis and inhibit cell growth in the HCT 116 cell line. Collectively, our data propose that J. procera leaves' methanolic extract has an anticancer role with the potential to guide future mechanistic studies.

Saccharine is a pharmacologically significant active scaffold for various biological activities, including antibacterial and anticancer activities. Herein, saccharinyl hydrazide ( 1 ) was synthesized and converted into 2-[(2Z)-2-(1,1-dioxo-1,2-dihydro-3H-1λ 6 ,2- benzothiazole-3-ylidene) hydrazinyl] acetohydrazide ( 5 ), which was employed as a key precursor for synthesizing a novel series of small molecules bearing different moieties of monosaccharides, aldehydes, and anhydrides. Potent biological activities were found against Staphylococcus and Escherichia coli , and the results indicated that compounds 6c and 10a were the most active analogs with an inhibition zone diameter of 30-35 mm . In cell-based anticancer assay over Ovcar-3 and M-14 cell lines, compound 10a was the most potent analog with IC 50 values of 7.64 ± 0.01 and 8.66 ± 0.01 µM, respectively. The Petra Orisis Molinspiration (POM) theoretical method was used to calculate the drug score of tested compounds and compare them with their experimental screening data. Theoretical DFT calculations were carried out in a gas phase in a set of B3LYP 6-311G (d,p). Molecular docking studies utilizing the MOE indicated the best binding mode with the highest energy interaction within the binding sites. The molecular docking for Ovcar-3 was carried out on the ovarian cancer protein (3W2S), while the molecular docking for M-14 melanoma was carried out on the melanoma cancer protein (2OPZ). The MD performed about 2ns simulations to validate selected compounds' theoretical studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abdellattif, Elkamhawy, Hagar, Hadda, Shehab, Mansy, Belal, Arief and Hussien.)

Three tridentate Schiff base ligands were synthesized from the reactions between 2-picolylamine and salicylaldehyde derivatives (3-ethoxy (OEt), 4-diethylamino (NEt 2 ) and 4-hydroxy (OH)). Complexes with the general formula Pt(N^N^O)Cl were obtained from reactions between the ligands and K 2 PtCl 4 . The ligands and their complexes were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. Further confirmation of the structure of Pt-OEt was achieved by single-crystal X-ray diffraction. The DMSO/chlorido exchange process at Pt-OEt was investigated by monitoring the change in conductivity, revealing very slow dissociation in DMSO. Moreover, solvent/chlorido exchange for Pt-OEt and Pt-NEt 2 were investigated by NMR spectroscopy in DMSO and DMSO/D 2 O; Pt-NEt 2 forms an adduct with DMSO while Pt-OEt forms adducts with DMSO and water. The DNA-binding behaviour of the platinum(ii) complexes was investigated by two techniques. Pt-NEt 2 has the best apparent binding constant. The intercalation mode of interaction with ct-DNA was suggested by molecular docking studies and the increase in the relative viscosity of ct-DNA with increasing concentrations of the platinum(ii) complexes. However, the gradual decrease in the relative viscosity over time at constant concentration of platinum(ii) complexes indicated a shift from intercalation to a covalent binding mode. Anticancer activities of the ligands and their platinum(ii) complexes were examined against two cell lines. The platinum(ii) complexes exhibit superior cytotoxicity to that of their ligands. Among the platinum(ii) complexes, Pt-OEt possesses the best IC 50 against both cell lines, its cytotoxicity being comparable to that observed for cisplatin. Cell cycle arrest in the HepG2 cell line upon treatment with Pt-OEt and Pt-NEt 2 was investigated and compared to that of cisplatin; the change in the cell accumulation patterns supports the presumption of an apoptotic cell death pathway. The optimized structures of the B-DNA trimer adducts with the platinum complexes showed hydrogen-bonding interactions between the ligands and nucleobases, affecting the inter-strand hydrogen bonding within the DNA, and highlighting the strong ability of the complexes to induce conformational changes in the DNA, leading to the activation of apoptotic cell death. In summary, the current study demonstrates promising new anticancer platinum(ii) complexes with highly flexible tridentate ligands; the functional groups on the ligands are important in tuning their DNA binding/anticancer properties., Competing Interests: The authors declare no conflicts of interest in this publication., (This journal is © The Royal Society of Chemistry.)

Purpose: To report functional and radiological outcomes of using primary fibular graft together with double plating in distal femoral fractures in the elderly., Methods: A retrospective study on 30 elderly patients with comminuted distal femoral fractures managed by primary fibular grafting and double plating through an anterior midline approach has been conducted. Only isolated distal femoral fractures type 33-A3, 33-C2, and 33-C3 were included. The patient's mean age was 75.3 years. Evaluation included operative time, blood loss, time to union, knee range of motion, Sanders scoring, and presence of complications., Results: The average follow-up period was 26.6 months. Mean intraoperative blood loss was 401 ml, and mean operative time was 216 min. All patients had a knee range of motion (90-120°) during follow-up. Time for union ranged from 16 to 23 weeks with a mean of 18.4 weeks, with no cases of non-union. A total of 22 patients (73.3%) showed excellent functional outcomes, and the remaining eight (26.7%) showed good functional outcomes according to the Sanders scoring system. Only two cases (6.6%) had superficial wound infections managed conservatively. No post-operative deformity, loss of reduction, or implant failure was observed until the end of follow-up period., Conclusion: Primary fibular grafting combined with double plating of comminuted distal femur fractures in patients above 70 years is an effective technique with higher rates of union and lower re-operation rates compared to other fixation modalities., (© 2022. The Author(s).)

Drug resistance in Mycobacterium tuberculosis has become a major challenge to the current regime of treatment as well as to the containment of the disease globally. The molecular and genetic studies identified frequently occurring point mutations in the virulent protein such as KatG of M. tuberculosis resulted in the development of isoniazid tolerance in the pathogen. This study aims to analyze the structural basis of the disease mutations available in the literature as well as to predict novel alteration in the KatG which may cause similar deleterious effects. Around 15 experimentally derived mutations were included in this study and pathogenic mutational landscapes containing 60 site-specific alterations were predicted using the available in silico techniques. The effects of these mutations on the stability of the protein were studied and an exhaustive docking study was conducted for each classified perturbations, which identify the highest changes in the binding energies in p.Meth255Ile among experimental and p.Ala222Arg in computationally predicted mutations. Furthermore, the structural effects on these substitutions were analyzed using the principles of molecular dynamic simulations each for a 100 ns time scale, which validated the interaction studies. The outcome of this study may enable the identification of the novel drug resistance-associated point mutations which were not previously reported and may contribute significantly in a variety of experimental studies as well as facilitate the process of drug design and discovery.Communicated by Ramaswamy H. Sarma.

Introduction  Chronic suppurative otitis media is one of the most common causes of reversible conductive hearing loss which can lead to necrosis of the ossicles. The incus, especially its long process, is the most common ossicle affected. Objectives  The present study aims to assess the use of glass ionomer cement for the reconstruction of the long process of the incus. Methods  The present study was conducted on 27 patients with chronic suppurative otitis media with central perforation with dry and quiescent ears with an eroded long process of the incus submitted to tympanoplasty. The audiological evaluations were done on all patients, including preoperative and postoperative evaluation of the air-bone gap; the average pure tone threshold was done 6 months postoperatively. Results  The average air pure tone threshold was 42.8 dB preoperatively and 22.5 dB postoperatively. The postoperative air pure tone thresholds were significantly smaller than the preoperative values ( p  < 0.01). The air-bone gap was 30.5 dB at 500 Hz, 31.6 dB at 1 KHz, and 24.1 dB at 2 kHz preoperatively, and 7.7 dB at 500 Hz, 7.2 dB at 1 KHz, and 7.1 dB at 2 kHz postoperatively at the end of 6 months of follow-up. There were significant hearing gains in the air-bone gap ( p  < 0.001). Conclusion  Glass ionomer cement is a useful and effective material for bridging the defect of the long process of the incus., Competing Interests: Conflict of interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Vanadium compounds have been set in various fields as anticancer, anti-diabetic, anti-parasitic, anti-viral, and anti-bacterial agents. This study reports the synthesis and structural characterization of oxidovanadium(IV)-based imidazole drug complexes by the elemental analyzer, molar conductance, magnetic moment, spectroscopic techniques, as well as thermal analysis. The obtained geometries were studied theoretically using density functional theory (DFT) under the B3LYP level. The DNA-binding nature of the ligands and their synthesized complexes has been studied by the electronic absorption titrations method. The biological studies were carried with in-vivo assays and the molecular docking method. The EPR spectra asserted the geometry around the vanadium center to be a square pyramid for metal complexes. The geometries have been confirmed using DFT under the B3LYP level. Moreover, the quantum parameters proposed promising bioactivity of the oxidovanadium(IV) complexes. The results of the DNA-binding revealed that the investigated complexes bind to DNA via non-covalent mode, and the intrinsic binding constant (K b ) value for the [VO(SO 4 )(MNZ) 2 ] H 2 O complex was promising, which was 2.0 × 10 6 M -1 . Additionally, the cytotoxic activity of the synthesized complexes exhibited good inhibition toward both hepatocellular carcinoma (HepG-2) and human breast cancer (HCF-7) cell lines. The results of molecular docking displayed good correlations with experimental cytotoxicity findings. Therefore, these findings suggest that our synthesized complexes can be introduced as effective anticancer agents.

Anti-dsDNA antibodies are a hallmark of systemic lupus erythematosus and are highly associated with its exacerbation. Cumulative evidence has suggested that somatic hypermutation contributes to the high-affinity reactivity of anti-dsDNA antibodies. Our previous study demonstrated that these antibodies are generated from germline precursors with low-affinity ssDNA reactivity through affinity maturation and clonal expansion in patients with acute lupus. This raised the question of whether such precursors could be subjected to immune tolerance. To address this, we generated a site-directed knock-in (KI) mouse line, G9gl, which carries germline-reverted sequences of the VH-DH-JH and Vκ-Jκ regions of patient-derived, high-affinity anti-dsDNA antibodies. G9gl heterozygous mice had a reduced number of peripheral B cells, only 27% of which expressed G9gl B-cell receptor (BCR). The remaining B cells harbored non-KI allele-derived immunoglobulin heavy (IgH) chains or fusion products of upstream mouse VH and the KI gene, suggesting that receptor editing through VH replacement occurred in a large proportion of B cells in the KI mice. G9gl BCR-expressing B cells responded to ssDNA but not dsDNA, and exhibited several anergic phenotypes, including reduced surface BCR and shortened life span. Furthermore, G9gl B cells were excluded from germinal centers (GCs) induced by several conditions. In particular, following immunization with methylated bovine serum albumin-conjugated bacterial DNA, G9gl B cells occurred at a high frequency in memory B cells but not GC B cells or plasmablasts. Collectively, multiple tolerance checkpoints prevented low-affinity precursors of pathogenic anti-dsDNA B cells from undergoing clonal expansion and affinity maturation in GCs., (© The Japanese Society for Immunology. 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study describes the preparation of graphitic carbon nitride (g-C 3 N 4 ), hematite (α-Fe 2 O 3 ), and their g-C 3 N 4 /α-Fe 2 O 3 heterostructure for the photocatalytic removal of methyl orange (MO) under visible light illumination. The facile hydrothermal approach was utilized for the preparation of the nanomaterials. Powder X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray (EDX), and Brunauer-Emmett-Teller (BET) were carried out to study the physiochemical and optoelectronic properties of all the synthesized photocatalysts. Based on the X-ray photoelectron spectroscopy (XPS) and UV-visible diffuse reflectance (DRS) results, an energy level diagram vs. SHE was established. The acquired results indicated that the nanocomposite exhibited a type-II heterojunction and degraded the MO dye by 97%. The degradation ability of the nanocomposite was higher than that of pristine g-C 3 N 4 (41%) and α-Fe 2 O 3 (30%) photocatalysts under 300 min of light irradiation. The formation of a type-II heterostructure with desirable band alignment and band edge positions for efficient interfacial charge carrier separation along with a larger specific surface area was collectively responsible for the higher photocatalytic efficiency of the g-C 3 N 4 /α-Fe 2 O 3 nanocomposite. The mechanism of the nanocomposite was also studied through results obtained from UV-vis and XPS analyses. A reactive species trapping experiment confirmed the involvement of the superoxide radical anion (O 2 •- ) as the key reactive oxygen species for MO removal. The degradation kinetics were also monitored, and the reaction was observed to be pseudo-first order. Moreover, the sustainability of the photocatalyst was also investigated.

Background: The chemokine CXCL12 and its two receptors (CXCR4 and CXCR7) are involved in inflammation and hematopoietic cell trafficking. This study was designed to investigate molecular docking interactions of four popular cardiovascular-active natural compounds; curcumin, resveratrol, quercetin, and eucalyptol; with these receptors and to predict their drug-like properties. We hypothesize that these compounds can modify CXCL12/CXCR4/CXCR7 pathway offering benefits for coronary artery disease patients., Methods: Docking analyses were carried and characterized by Molecular Environment (MOE) software. Protein Data Bank ( http://www.rcsb.org/ ) has been retrieved from protein structure generation and crystal structures of CXCR4 and CXCR7 receptors (PDB code = 3ODU and 6K3F). The active sites of these receptors were evaluated and extracted from full protein and molecular docking protocol was done for compounds against them. The presented parameters included docking scores, ligand binding efficiency, and hydrogen bonding. The pharmacokinetic/toxic properties (ADME/T) were calculated using SwissADME, ProTox-II, and Pred-hERG softwares to predict drug-like properties of the compounds. The thermochemical and molecular orbital analysis, and molecular dynamics simulations were also done., Results: All compounds showed efficient interactions with the CXCR4 and CXCR7 receptors. The docking scores toward proteins 3ODU of CXCR4 and 6K3F of CXCR7 were - 7.71 and - 7.17 for curcumin, - 5.97 and - 6.03 for quercetin, - 5.68 and - 5.49 for trans-resveratrol, and - 4.88 and - 4.70 for (1 s,4 s)-eucalyptol respectively indicating that all compounds, except quercetin, have more interactions with CXCR4 than with CXCR7. The structurally and functionally important residues in the interactive sites of docked CXCR4-complex and CXCR7-complex were identified. The ADME analysis showed that the compounds have drug-like properties. Only (1 s,4 s)-Eucalyptol has potential weak cardiotoxicity. The results of thermochemical and molecular orbital analysis and molecular dynamics simulation validated outcomes of molecular docking study., Conclusions: Curcumin showed the top binding interaction against active sites of CXCR4 and CXCR7 receptors, with the best safety profile, followed by quercetin, resveratrol, and eucalyptol. All compounds demonstrated drug-like properties. Eucalyptol has promising potential because it can be used by inhalation or skin massage. To our knowledge, this is the first attempt to find binding interactions of these natural agents with CXCR4 and CXCR7 receptors and to predict their druggability., (© 2022. The Author(s).)

Four new drug-based oxidovanadium (IV) complexes were synthesized and characterized by various spectral techniques, including molar conductance, magnetic measurements, and thermogravimetric analysis. Moreover, optimal structures geometry for all syntheses was obtained by the Gaussian09 program via the DFT/B3LYP method and showed that all of the metal complexes adopted a square-pyramidal structure. The essential parameters, electrophilicity (ω) value and expression for the maximum charge that an electrophile molecule may accept (ΔN max ) showed the practical biological potency of [VO(CTZ) 2 ] 2H 2 O. The complexes were also evaluated for their propensity to bind to DNA through UV-vis absorption titration. The result revealed a high binding ability of the [VO(CTZ) 2 ] 2H 2 O complex with K b = 1.40 × 10⁶ M -1 . Furthermore, molecular docking was carried out to study the behavior of the VO (II) complexes towards colon cancer cell (3IG7) protein. A quantitative structure-activity relationship (QSAR) study was also implemented for the newly synthesized compounds. The results of validation indicate that the generated QSAR model possessed a high predictive power (R 2 = 0.97). Within the investigated series, the [VO(CTZ) 2 ] 2H 2 O complex showed the greatest potential the most selective compound comparing to the stander chemotherapy drug.

Study Design: Prospective case series., Purpose: To describe a new technique for anterior column reconstruction after kyphectomy in myelomeningocele patients using titanium mesh cage and to evaluate outcomes and complications., Methods: Sixteen patients with severe dorsolumbar kyphosis 2 ry to myelomeningocele were enrolled with a mean age of 10.1 years. Kyphectomy procedure and long spinopelvic fixation were done, titanium mesh cage was used to reconstruct the anterior column. Operative time and intraoperative blood loss were calculated. Using the Cobb method, pre and postoperative measurements of local/regional kyphosis were done. Degree and mean percentage of correction were calculated. Anterior intervertebral height of the kyphotic area was also measured. The mean follow-up period was 27 months., Results: Operative time was 271.3 min ± 25, and estimated intraoperative blood loss was 781.3 mL ± 92.3. On average, 2.5 vertebrae were resected. All 16 patients were able to lie supine immediately postoperatively. The mean preoperative local/regional kyphosis was 107.5°, and 106.9° respectively, corrected to 22.5° and 28.8° postoperatively, with a mean degree of correction of 85° and 78.1° respectively. Mean preoperative anterior intervertebral height was 3.54 cm, improved to 4.64 cm postoperatively. Only 2 cases had a superficial wound infection managed conservatively. At the latest follow-up, no loss of correction pseudoarthrosis occurred, and all patients showed solid fusion., Conclusion: Titanium mesh cage is an efficient, easy method for anterior reconstruction following kyphectomy in myelomeningocele patients, to maintain postoperative correction., Level of Evidence: Therapeutic studies, Level IV study., (© The Authors, published by EDP Sciences, 2022.)

Study Design: Prospective case series., Purpose: To assess the outcomes of pars repair surgery using pedicle screws and laminar hooks., Methods: This study was conducted on 22 patients with symptomatic lumbar spondylolysis. Curettage of the fibrocartilage in the defect and drilling of the sclerotic bone ends were done, followed by impaction of cancellous bone graft. Pedicle screws were inserted bilaterally in the corresponding pedicles and connected to a laminar hook via rods (screw-rod-hook fixation). The intensity of back pain and the functional outcome were assessed using the visual analog scale (VAS) and the Oswestry disability index (ODI). Plain radiographs were performed immediately postoperatively and after 3 and 6 months. CT scan was done at the final follow-up to assess pars healing. The mean follow-up period was 27 months., Results: The mean preoperative VAS and ODI were 7.4 ± 0.8 and 64.8 ± 6.7, which improved to 2.4 ± 0.8 and 20 ± 6 respectively at the final follow-up (P < 0.001). Healing of the defect was found in 19 patients at the final follow-up. Non-fusion with graft resorption was noticed in the remaining 3 cases (13.6%). However, postoperative VAS and ODI values improved even in the radiologically non-fused patients., Level of Evidence: Therapeutic study, Level IV., Conclusion: Pars repair using pedicle screws and laminar hooks is a relatively simple yet effective procedure., (© The Authors, published by EDP Sciences, 2022.)

In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR&#95;1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R 2 = 0.96 and Q 2 = 0.57. Leave one out (LOO) cross-validation (R 2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (-11.265, -10.532, -10.422, -10.827, -10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors.

In this study, we used oxazinethione as a perfect precursor to synthesize new pyrimidine and pyrazole derivatives with potent biological activities. Biological activities were determined for all compounds against A. flavus, E. coli, S. aureus, and F. moniliform . Compounds 3 , 4a-b , and 5 exhibited higher activities toward A. flavus, E. coli, S. aureus, and F. moniliform ; this was indicated through the MIC (minimum inhibitory concentration). At the same time, anticancer activities were determined through four cell lines, Ovcar-3, Hela, MCF-7, and LCC-MMk. The results obtained indicated that compound 5 was the most potent compound for both cell lines. Molecular docking was studied by the MOE (molecular operating environment). The in silico ADME of compounds 2 and 5 showed good pharmacokinetic properties. The present research strengthens the applicability of these compounds as encouraging anticancer and antibacterial drugs. Moreover, JAGUAR module MD simulations were carried out at about 100 ns. In addition, spectroscopic studies were carried out to establish the reactions of the synthesized structure derivatives.

Three new uranyl complexes [(UO2)(OAc)2(CMZ)], [(UO2)(OAc)2(MP)] and [(UO2)(OAc)2(SCZ)] were synthesized and characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, powder XRD analysis, and molar conductivity. The IR analysis confirmed binding to the metal ion by the sulfur and ethoxy oxygen atoms in the carbimazole (CMZ) ligand, while in the 6-mercaptopurine (MP) ligand, the sulfur and the N7 nitrogen atom of a purine coordinated binding to the metal ion. The third ligand showed a 1:1 molar ratio and bound via sulfonamide oxygen and the nitrogen of the pyrimidine ring. Analysis of the synthesized complexes also showed that acetate groups had monodentate binding to the (UO22+). Density Functional Theory (DFT) calculations at the B3LYP level showed similar structures to the experimental results. Theoretical quantum parameters predicted the reactivity of the complexes in the order, [(UO2)(OAc)2(SCZ)] > [(UO2)(OAc)2(MP)]> [(UO2)(OAc)2(CMZ)]. DNA binding studies revealed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb) among the uranyl complexes. Additionally, strong binding of the MP and CMZ metal complexes to human serum albumin (HSA) were observed by both absorbance and fluorescence approaches. The antibacterial activity of the complexes was also evaluated against four bacterial strains: two gram-negative; Escherichia coli and Klebsiella pneumonia, and two gram-positive; Staphylococcus aureus and Streptococcus mutans. [(UO2)(OAc)2(MP)] had the greatest antibacterial activity against Klebsiella pneumonia, the gram-positive bacteria, with even higher activity than the standard antibiotic. In vitro cytotoxicity tests were also performed against three human cancer lines, and revealed the most cytotoxic complexes to be [(UO2)(OAc)2(SCZ)], which showed moderate activity against a colon cancer cell line. Thus, uranyl addition enhances the antibacterial and anticancer properties of the free ligands., Competing Interests: The authors have declared that no competing interests exist.

Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6-311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screening of their ability to bind to calf thymus DNA (CT-DNA) showed that the complexes interact with CT-DNA through an intercalation mode, for which the K b values ranged from 1 × 10 6 to 3.33 × 10 5 M -1 . The anticancer activities of the Schiff base ligands and their uranyl complexes against two ovarian (Ovcar-3) and melanoma cell lines (M14) were investigated, and the results indicated that uranyl complexes exhibit better results than the Schiff base ligands. Molecular docking identified the distance, energy account, type, and position of links contributing to the interactions between these complexes and two different cancer proteins (3W2S and 2OPZ).

In the search for novel, metal-based drug complexes that may be of value as anticancer agents, five new transition metal complexes of sulfaclozine (SCZ) with Cu(II), Co(II), Ni(II), Zn(II), and Fe(II) were successfully synthesized. The chemical structure of each complex was characterized using elemental analysis (CHN), IR spectroscopy, UV-Vis spectroscopy, thermogravimetric analysis (TGA), and electronic paramagnetic resonance (EPR) spectroscopy. IR spectra indicated that the donor atoms were one sulfonyl oxygen atom and one pyrazine nitrogen atom, which associated with the metal ions to form a stable hexagonal coordination ring. The metal-ligand stability constant (K f ) revealed that Cu(II) and Ni(II) have good coordination stability among the metal compounds. Theoretical studies using DFT/B3LYP were performed to further validate the proposed structures. The obtained results indicated that Cu(II) has a trigonal bipyramidal geometry, whereas Fe(II), Co(II), and Ni(II) have an octahedral structure, while Zn(II) has a tetrahedral arrangement. The bio-activities of the characterized complexes were evaluated using DNA binding titration and molecular docking. The binding constant values for the metal complexes were promising, with a maximum value for the copper metal ion complex, which was 9 × 10 5 M -1 . Molecular docking simulations were also carried out to evaluate the interaction strength and properties of the synthesized metal complexes with both DNA and selected cancer-relevant proteins. These results were supported by in vitro cytotoxicity assays showing that the Cu(II) and Ni(II) complexes display promising antitumor activity against colon and breast cancer cell lines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation, though no other collaboration, with the authors AE and MJ., (Copyright © 2021 Sharfalddin, Emwas, Jaremko and Hussien.)

A set of copper(I) coordination compounds with general formula [CuBr(PPh 3 )(dppz-R)] (dppz-R = dipyrido[3,2-a:2',3'-c]phenazine ( Cu-1 ), 11-nitrodipyrido[3,2-a:2',3'-c]phenazine ( Cu-2 ), 11-cyanodipyrido[3,2-a:2',3'-c]phenazine ( Cu-3 ), dipyrido[3,2-a:2',3'-c]phenazine-11-phenone ( Cu-4 ), 11,12-dimethyldipyrido[3,2-a:2',3'-c]phenazine ( Cu-5 )) have been prepared and characterized by elemental analysis, 1 H-NMR and 31 P-NMR spectroscopies as well as mass spectrometry. The structure of Cu-1 was confirmed by X-ray crystallography. The effect of incorporating different functional groups on the dppz ligand on the binding into CT-DNA was evaluated by absorption spectroscopy, fluorescence quenching of EtBr-DNA adducts, and viscosity measurements. The functional groups affected the binding modes and hence the strength of binding affinities, as suggested by the changes in the relative viscosity. The differences in the quenching constants (K sv ) obtained from the fluorescence quenching assay highlight the importance of the functional groups in altering the binding sites on the DNA. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA changing with the different functional groups. Evaluation of the anticancer activities of the five copper compounds against two different cancer cell lines (M-14 and MCF-7) indicated the importance of the functional groups on the dppz ligand on the anticancer activities. Among the five copper complexes, the cyano-containing complex ( Cu-3 ) has the best anticancer activities.

Selenium containing heterocyclic compounds gained great interest as bioactive molecules as of late. This report explores the design, synthesis, characterization, and antimicrobial screening of new pyridine derivatives endowed with selenium moieties. A one-pot multicomponent system with a solvent-free, microwave irradiation environment was employed to afford this series. The spectroscopic techniques were exploited to verify the structures of the synthesized derivatives. Additionally, the agar diffusion method was employed to determine the antimicrobial activity of all the desired compounds. Of all the synthesized molecules, 9b , 12b , 14f , and 16d exhibited well to remarkable antibacterial and antifungal activities. Moreover, derivative 14f demonstrated the most potent antibacterial and antifungal performance. The results were also supported by molecular docking studies, utilizing the MOE (molecular operating environment) which revealed the best binding mode with the highest energy interaction within the binding pocket. Lastly, theoretical DFT calculations were carried out in a gas phase at B3LYP 6-311G (d,p) basis set to predict the molecular geometries and chemical reactivity descriptors. DFT results have been used to illustrate that molecular docking findings and biological activity assessments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Abdellattif, Abdel-Rahman, Arief, Mouneir, Ali, Hussien, Okasha, Afifi and Hagar.)

The sulfonic esters of N-oxyimides are a group of compounds with a wide range of biological activities, as well as a unique reactivity toward amines. They undergo this reaction with primary amines and other nucleophilic reagents according to a Lossen-like rearrangement. The reaction is initiated by nucleophilic attack on a carbonyl group in the succinimide ring followed by isocyanate formation, which next interacts with another nucleophile molecule forming an addition product (e.g., ureido or urethane derivative). However, the secondary amines are also susceptible to other reactions leading to products containing the maleimide ring formed by sulphonic acid elimination. In the case of tertiary amines, this reaction is predominant. To explain the phenomenon of the reactivity of the N- oxyimides toward different types of amines, we employed various spectroscopic and X-ray approaches as well as DFT calculation. Results suggest that the basicity of the amine used for the reaction plays a crucial role in the reaction mechanism that eventually dominates the entire chemical process. Moreover, we applied molecular docking to investigate the ability of the products to act as serine protease inhibitors using human leukocyte elastase (HLE)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kijewska, Sharfalddin, Jaremko, Cal, Setner, Siczek, Stefanowicz, Hussien, Emwas and Jaremko.)

A set of five gold complexes with the general formula Au(PR 3 )(C≡C-C 6 H 4 -4-R') (R = PPh 3 , R' = -CHO (1), R = PCy 3 , R' = -CHO (2), R = PPh 3 , R' = -N=CH-C 6 H 4 -2-OH (3), R = PPh 3 , R' = -N=CH-C 6 H 4 -4-OH (4), R = PCy 3 , R' = -N=CH-C 6 H 4 -2-OH (5)) were synthesized and characterized by elemental analysis, 1 H-NMR spectroscopy, 31 P-NMR spectroscopy, and mass spectrometry. The structures of complexes 2 and 5 were determined by X-ray crystallography. The effects of the structural modifications on the protein binding affinities and anticancer activities of the five gold complexes were assessed. Fluorescence quenching experiments to assess binding to human serum albumin (HSA) revealed that the Schiff base complexes (3, 4, and 5) had binding constants that were superior to their parent aldehyde complexes and highlighted the position of the hydroxy group because complex 4 (4-hydroxy) had a binding constant 6400 times higher than complex 3 (2-hydroxy). The anticancer activities of the complexes against the OVCAR-3 (ovarian carcinoma) and HOP-62 (non-small-cell lung) cancer cell lines showed that the Schiff bases (3-5) were more cytotoxic than the aldehyde-containing complexes (1 and 2). Notably, compound 4 had cytotoxic activity comparable to that of cisplatin against OVCAR-3, demonstrating the significance of the para position for the hydroxy group. Molecular docking studies against the enzyme thioredoxin reductase (TrxR) and human serum albumin were conducted, with docking scores in good agreement with the experimental data. The current study highlights how small structural modifications can alter physiochemical and anticancer properties. Moreover, this simple design strategy using the aldehyde group can generate extensive opportunities to explore new gold(I)-based anticancer drugs via condensation, cyclization, or nucleophilic addition reactions of the aldehyde.

Ruthenium(II) arene complexes of the general formula [RuCl(η 6 - p -cymene)(diamine)]PF 6 (diamine = 1,2-diaminobenzene ( 1 ), 2,3-diaminonaphthalene ( 2 ), 9,10-diaminophenanthrene ( 3 ), 2,3-diaminophenazine ( 4 ), and 1,2-diaminoanthraquinone ( 5 ) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2 . The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2 . Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru-N guanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC 50 ) values comparable to or better than cisplatin against three cell lines.

Purpose: Optimum management of displaced intra-articular calcaneal fractures (DIACF) still controversial. Open surgery carries the risk of wound complications, while non-operative management has a high incidence of arthrosis. To avoid these complications, minimally invasive and percutaneous fixation was introduced. The purpose of this study was to prospectively evaluate the short term clinical and radiological outcomes after closed reduction and percutaneous fixation of DIACF using K-wires., Patients and Methods: Outcomes of twenty patients were evaluated at the final follow up. A functional assessment using the AOFAS scoring system. Radiological parameters recorded included three angles (Böhler's, Gissane and posterior facet inclination angles) and three distances (calcaneal length, height and width). Any complications were reported at any follow-up., Results: The mean patient's age was 33 ± 15.2 years, 8 (40%) patients with type II fractures, 10 (50%) patients with type III fractures, and 2 (10%) with type IV fracture according to Sanders classification. After a mean follow-up of 9 months, the mean AOFAS score was 84, excellent in 9 patients (45%), good in 9 (45%), and fair in 2 (10%). At the final follow-up the Böhler's angle, Gissane angle and PFIA was 25.1° ± (5.2), 119.9° ± (9.4) and 51.7° ± (5.9) respectively and the calcaneal height, length and width was 41.8 mm ± (2.1), 75.1 mm ± (3.01) and 40.9 mm ± (2.6) respectively. We had no cases of deep infection, 20% had significant subtalar arthritis., Conclusion: The closed reduction and percutaneous fixation technique for DIACF management offered acceptable clinical and radiographic outcomes, with fewer complications when compared to other management options., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Forward osmosis (FO) has received widespread recognition in the past decade due to its potential low energy production of water. This study presents a new model analysis for predicting the water flux in FO systems when inorganic-based draw solutions are used under variable experimental conditions for using a laboratory scale cross-flow single cell unit. The new model accounts for the adverse impact of concentration polarization (both ICP and ECP) incorporating the water activity by Pitzer to calculate the bulk osmotic pressures. Using the water activity provides a better correlation of experimental data than the classical van't Hoff equation. The nonlinear model also gave a better estimate for the structural parameter factor (S) of the membrane in its solution. Furthermore, the temperature and concentration of both the draw and feed solutions played a significant role in increasing the water flux, which could be interpreted in terms of the mass transfer coefficient representing ECP; a factor sensitive to the hydraulics of the system. The model provides greatly improved correlations for the experimental water fluxes.

A new series of polyurea derivatives and its nanocomposites were synthesised by the solution polycondensation method through the interaction between 4(2-aminothiazol-4-ylbenzylidene)-4-(tert-butyl) cyclohexanone and diisocyanate compound in pyridine. The PU 1-3 structure was confirmed using Fourier transform-infrared (FTIR) spectroscopy and characterised by solubility, viscometry, gel permeation chromatography (GPC), and X-ray diffraction (XRD) analysis. In addition, PU 1-3 was evaluated by TGA. Polyurea-TiO 2 nanocomposites were synthesised using the same technique as that of PU 1-3 by adding TiO 2 as a nanofiller. The thermal properties of PU 2 TiO 2 a-d were evaluated by TGA. Moreover, the morphological properties of a selected sample were examined by SEM and TEM. In addition, PU 1-3 and PU 2 TiO 2 a-d were examined for antimicrobial activity against certain bacteria and fungi. The PU 1-3 showed antibacterial activity against some of the tested bacteria and fungi, as did PU 2 TiO 2 a-d, which increased with the increase in TiO 2  content. Furthermore, molecular docking studies were displayed against all PU 1-3 derivatives against two types of proteins. The results show that the increase in the strength of π-H interactions and H-donors contributed to improved binding of PU2 compared to PU1 andPU 3. The docking of 1KZN against the tested polymers suggests an increase in the docking score of PU 2, then PU 1 , and PU 3 , which is in agreement with the antibacterial study., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The spermatozoa are transcriptionally dormant entities which have been recognized to be an archive of mRNA, coding for a variety of functionally crucial cellular proteins. This significant repository of mRNA is predicted to be associated with early embryogenesis and postfertilization. The mRNA transcripts which are tagged with minisatellites have been involved in the regulation of the gene functions as well as their organization. However, very little information is available regarding the expression of the transcripts tagged with minisatellites in spermatozoa. Therefore, in order to understand the functions and the conformational behavior of the proteins expressed from these minisatellite-tagged transcripts, we have performed a detailed in silico analysis using the sequences of the transcripts. The protein predicted from KF274549 showed the functionalities similar to uncharacterized C4orf26 proteins, while that obtained from KF274557 predicted to be a metallophosphoesterase. Furthermore, the structural folds in the structure of these predicted proteins were analyzed by using the homology modeling and their conformational behaviors in the explicit water conditions were analyzed by using the techniques of Molecular Dynamics (MD) simulations. This detailed analysis will facilitate the understanding of these proteins in the spermatozoon region and can be used for uncovering other attributes of the metabolic network., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Mohd Shahbaaz et al.)

The emergence of the drug-resistant mechanisms in Mycobacterium tuberculosis poses the biggest challenges to the current therapeutic measures, which necessitates the identification of new drug targets. The Hypothetical Proteins (HPs), a class of functionally uncharacterized proteins, may provide a new class of undiscovered therapeutic targets. The genome of M. tuberculosis contains 1000 HPs with their sequences were analyzed using a variety of bioinformatics tools and the functional annotations were performed. The functions of 662 HPs were successfully predicted and further classified 483 HPs as enzymes, 141 HPs were predicted to be involved in the diverse cellular mechanisms and 38 HPs may function as transporters and carriers proteins. Furthermore, 28 HPs were predicted to be virulent in nature. Amongst them, the HP P95201, HP P9WM79, HP I6WZ30, HP I6 × 9T8, HP P9WKP3, and HP P9WK89 showed the highest virulence scores. Therefore, these proteins were subjected to extensive structure analyses and dynamics of their conformations were investigated using the principles of molecular dynamics simulations, each for a 150 ns time scale. This study provides a deeper understanding of the undiscovered drug targets and the generated outputs will facilitate the process of drug design and discovery against the infection of M. tuberculosis., Competing Interests: Declaration of Competing Interest Authors declare no competing interests., (Copyright © 2020. Published by Elsevier Ltd.)

Feed additives are used frequently in variable combinations to maximize broiler productivity and consumer safety. Therefore, we evaluated the efficiency of feed additives used in four different diets: a basal diet, a probiotic (PRO-PAC ® ) supplement diet, an egg yolk purified immunoglobulin Y (IgY) supplemented diet, and a combination of IgY and PRO-PAC ® supplement ( n = 15 for each group). We assessed the improvement of behavioral and hematological parameters of Ross broilers before and after an immune stress challenge using lipopolysaccharide (LPS). Behavioral as well as physiological parameters were analyzed. The standing frequency was the highest ( P < 0.05) in broilers supplemented with a combination of probiotics and IgY. Likewise, latency approach score to a novel object improved ( P < 0.01) in the combination group at week-3. After intraperitoneal injection of LPS, this combination group achieved the best gait score at week-3, followed by week-5, compared to birds fed the basal diet. The heterophil/lymphocyte (H/L) ratio, heterophil differential count, and eosinophil differential count in the basal diet group that was challenged with LPS were significantly increased ( P < 0.01, P < 0.001, P < 0.05, respectively) compared to the combination groups. Therefore, we concluded that the combination of IgY and probiotics can significantly improve the behavior and the underlying physiological parameters of Ross broilers. Consequently, this combination can improve the broilers' health, welfare and produce a safe meat free from harmful chemical residues., (Copyright © 2020 Rehan, Youssef, Abdel-Rahman, Fahmy, Ahmed, Ahmed, Maky, Diab, Shanab, Alkahtani, Abdel-Daim, Hassan, Rehan, Hussien, Eleiwa, Elnagar, Abdeen and Hesham.)

3,6-Diethynyl-9,10-diethoxyphenanthrene ( 4 ) was synthesized from phenanthrene and employed in the synthesis of the binuclear gold(I) alkynyl complexes (R 3 P)Au(C≡C-3-[C 14 H 6 -9,10-diethoxy]-6-C≡C)Au(PR 3 ) (R = Ph ( 5a ), Cy ( 5b )). The diyne 4 and complexes 5a and 5b were characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. UV-Vis spectroscopy studies of the metal complexes and precursor diyne show strong p à p* transitions in the near UV region that red shift by ca. 50 nm upon coordination at the gold centers. The emission spectrum of 4 shows an intense fluorescence band centered at 420 nm which red shifts, slightly upon coordination of 4 to gold. Binding studies of 4 , 5a, and 5b against calf thymus DNA were carried out, revealing that 4, 5a, and 5b have >40% stronger binding affinities than the commonly used intercalating agent ethidium bromide. The molecular docking scores of 4 , 5a, and 5b with B-DNA suggest a similar trend in behavior to that observed in the DNA-binding study. Unlike the ligand 4 , promising anticancer properties for 5a and 5b were observed against several cell lines; the DNA binding capability of the precursor alkyne was maintained, and its anticancer efficacy enhanced by the gold centers. Such phenanthrenyl complexes could be promising candidates in certain biological applications because the two components (phenanthrenyl bridge and metal centers) can be altered independently to improve the targeting of the complex, as well as the biological and physicochemical properties.

Background: The synthesis of a novel series of oxadiazine-4-thione biological molecules was executed through the incorporation of the ortho-, meta-, and para-benzoyl isocyanates to the tetrabromophthalimide nucleus., Objectives: A one-pot multicomponent methodology in a solvent-free microwave irradiation environment was employed to afford this series of oxadiazine-4-thione, deriving a comparison with the conventional method. Subsequently, the yielded derivatives were subjected to further biological assessment., Materials and Methods: The acquired results denoted that the one-pot procedure, which delivered products in a 2-4 min. interval, was more efficient in evaluation against the classical method, which consumed a 1-2:30 hr. interval., Results: The application of the antibacterial analyses was subjected to all the compounds, resulting in molecules 6a and 6c demonstrating the highest activity regarding Aspergillus Favus; molecules 5b and 5c exhibiting an equivalent level of activity towards E-coli and Fusarium Moniliform; and molecules 4b, 4c, 5b, and 5c presenting an identical level of activity to the aforementioned derivatives involving Staphylococcus. Concluison: Molecular modeling studies by the MOE, the preceding antibacterial behavior was conducted to advocate the newly prepared compounds. Moreover, the spectroscopic approaches were exploited to verify and establish the structures and mechanisms of the synthesized derivatives' reactions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Abstract: The current outbreak of the highly transmittable and life-threatening severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved rapidly and posed a global health emergency. Many clinical trials are now being conducted to test possible therapies. To assist this, virtual screening via molecular docking was performed on several FDA-approved drugs, previously used in epidemics, and the top ten compounds were selected. These ten well-characterized drugs, previously used to treat malaria and Ebola infections, were screened based on their interactions with the SARS-CoV-2 ACE2 receptor and 3C-like protease. Compared to the other nine medicines, brincidofovir, an ether lipid ester analog of cidofovir with potent antiviral activity, showed the highest docking scores and binding interactions. Therefore, brincidofovir is worth further investigations and clinical trials as a possible therapeutic agent for the COVID-19 disease caused by the novel SARS-CoV-2., Competing Interests: Conflict of interestThe authors declare no competing financial interest., (© Springer-Verlag GmbH Austria, part of Springer Nature 2020.)

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by eosinophilic inflammation and polyposis at the nose and paranasal sinus and a high concentration of IgE in nasal polyps (NPs). The causative antigen and pathogenesis of CRSwNP remain unknown., Objective: We aimed to identify reactive allergens of IgE antibodies produced locally in NPs of patients with CRSwNP. We also attempted to unravel the differentiation pathway of IgE-producing B cells in NPs., Methods: IgE reactivity of patients with CRSwNP was investigated by characterizing single cell-derived mAbs. T-cell response against identified allergens was investigated in vitro. NP-infiltrating lymphocytes were characterized by using flow cytometry. Immunoglobulins expressed in NPs were analyzed by using high-throughput DNA sequencing for immunoglobulin., Results: About 20% of isolated IgE antibodies derived from NP-residing plasmablasts specifically recognized surface determinants of nasal bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. A T H 2 response against S pyogenes was observed in patients with CRSwNP. Flow cytometric analysis revealed sizable germinal center B-like cell and plasmablast subsets expressing IgE on the cell surface in NPs. High-throughput DNA sequencing immunoglobulin analysis highlighted the clonal connectivity of IgE with IgG and IgA 1 . The Iε-Cα 1 circle transcript was detected in NPs., Conclusions: In patients with CRSwNP, nasal bacteria-reactive B cells differentiate into IgE-producing B cells through IgG/IgA 1 -IgE class switching, suggesting that allergic conversion of the mucosal response against nasal bacteria underlies disease pathogenesis., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The evolutional process of disease-associated autoantibodies in systemic lupus erythematosus (SLE) remains to be established. Here we show intraclonal diversification and affinity maturation of anti-nuclear antibody (ANA)-producing B cells in SLE. We identified a panel of monoclonal ANAs recognizing nuclear antigens, such as double-stranded DNA (dsDNA) and ribonucleoproteins (RNPs) from acute SLE subjects. These ANAs had relatively few, but nonetheless critical mutations. High-throughput immunoglobulin sequencing of blood lymphocytes disclosed the existence of sizable ANA lineages shearing critical mutations intraclonally. We further focused on anti-DNA antibodies, which are capable to bind to both single-stranded (ss) and dsDNA at high affinity. Crystal structure and biochemical analysis confirmed a direct role of the mutations in the acquisition of DNA reactivity and also revealed that these anti-DNA antibodies recognized an unpaired region within DNA duplex. Our study unveils the unique properties of high-affinity anti-DNA antibodies that are generated through antigen-driven affinity maturation in acute phase of SLE.

New binuclear chromium (III) niacinamide compound with chemical formula [Cr 2 (Nic)(Cl) 6 (H 2 O) 4 ]·H 2 O was obtained upon the reaction of chromium (III) chloride with niacinamide (Nic) in methanol solvent at 60°C. The proposed structure was discussed with the help of microanalytical analyses, conductivity, spectroscopic (FT-IR and UV-vis.), magnetic calculations, thermogravimetric analyses (TG/TGA), and morphological studies (X-ray of solid powder and scan electron microscopy. The infrared spectrum of free niacinamide in comparison with its chromium (III) compound indicated that the chelation mode occurs via both nitrogen atoms of pyridine ring and primary -NH 2 group. The efficiency of chromium (III) niacinamide compound in decreasing of glucose level of blood and HbA1c in case of diabetic rats was checked. The ameliorating gluconeogenic enzymes, lipid profile and antioxidant defense capacities are considered as an indicator of the efficiency of new chromium (III) compound as antidiabetic drug model., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Oil removal from water is a highly important area due to the large production rate of emulsified oil in water, which is considered one of the major pollutants, having a negative effect on human health, environment and wildlife. In this study, we have reported the application of high quality carbon nanotube bundles produced by an injected vertical chemical vapor deposition (IV-CVD) reactor for oil removal. High quality, bundles, super hydrophobic, and high aspect ratio carbon nanotubes were produced. The average diameters of the produced CNTs ranged from 20 to 50 nm while their lengths ranged from 300 to 500 μm. Two types of CNTs namely, P-CNTs and C-CNTs, (Produced CNTs from the IV-CVD reactor and commercial CNTs) were used for oil removal from water. For the first time, thermogravimetric analysis (TGA) was conducted to measure maximum oil uptake using CNT and it was found that P-CNT can take oil up to 17 times their weight. The effect of adsorbent dosage, contact time, and agitation speed were examined on the oil spill clean-up efficiency using batch sorption experiments. Higher efficiency with almost 97% removal was achieved using P-CNTs compared to 87% removal using C-CNTs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Seahorse diversity (genus Hippocampus, Family Syngnathidae), species identification, size composition and sexual dimorphism were studied from November 2012 to March 2013 in selected coastal waters around Kota Kinabalu, Sabah and the local market trade. Six species of seahorses were identified in the study: (1) Hippocampus barbouri, (2) Hippocampus comes, (3) Hippocampus kelloggi, (4) Hippocampus kuda, (5) Hippocampus spinosissimus and (6) Hippocampus trimaculatus. All six species were sold at the local market, and the dried seahorses were obtained mainly by local fishermen using trawl by-catch method and traded as traditional medicine, souvenirs and other uses. Four species were identified by direct samplings in various different habitats of Kota Kinabalu coastal waters: (1) H. barbouri, (2) H. comes, (3) H. kuda, and (4) H. spinosissimus. Based on the results, H. comes was the largest in size among the four fresh/live species found (mean standard length [SL]: 148.25±1.26 mm), whereas H. barbouri was the smallest species (mean SL: 129±7.81 mm). For the dried samples, H. kelloggi was the largest (mean SL: 245.25±14.55 mm) and H. barbouri was the smallest (mean SL: 127.21±10.01 mm). No significant difference (p>0.05) was observed between the lengths of males and females in every seahorse species, and there was no sexual size dimorphism in any of the species. The findings from the study are significant to provide baseline data for the conservation efforts of these unique marine teleost.

Early detection of kidney injury in neonates is very important for appropriate management and prevention of serious complications; however, commonly used detectors as creatinine and blood urea nitrogen (BUN) do not directly reflect early renal cell injury. Serum cystatin-C (Cys-C) and beta 2-microglobulin (Β2M), serum creatinine and BUN were assessed in 20 neonates who developed renal impairment after admission to the neonatal intensive care unit and 10 healthy neonates. The means of serum Cys-C, Β2M and creatinine on Day 1 of admission in the cases and control groups were 2.15 ± 0.52 vs 0.45 ± 0.19, 7.18 ± 2.36 vs 1.92 ± 0.41 and 0.81 ± 0.07 vs 0.53 ± 0.20, respectively, with P-value <0.05 in only Cys-C and Β2M. We conclude that serum Cys-C and Β2M are suggested as simple and accurate markers for the early diagnosis of kidney injury in neonates than serum creatinine.