Unusual location of myxopapillary ependymoma in the sacrum: Case report and review of the literature.

Myxopapillary ependymoma, a rare variant of ependymoma, commonly occurs in the conus medullaris or filum terminale. The rarity of these tumors can make their diagnosis and treatment challenging. This case report presents an atypical occurrence of myxopapillary ependymoma within the sacrum in a 68-year-old patient presented with a 3-month history of persistent left-sided low back pain radiating to the legs and fecal dysfunction. The patient underwent a sacral laminectomy and subtotal excision of the tumor, followed by adjuvant radiotherapy with favorable outcomes. This report highlights the significance of tailored approaches for unconventional tumor locations emphasizes the potential benefits of multimodal treatment strategies and provides insights from a comprehensive literature review on similar cases.

Chemical library design, QSAR modeling and molecular dynamics simulations of naturally occurring coumarins as dual inhibitors of MAO-B and AChE.

Coumarins are a highly privileged scaffold in medicinal chemistry. It is present in many natural products and is reported to display various pharmacological properties. A large plethora of compounds based on the coumarin ring system have been synthesized and were found to possess biological activities such as anticonvulsant, antiviral, anti-inflammatory, antibacterial, antioxidant as well as neuroprotective properties. Despite the wide activity spectrum of coumarins, its naturally occurring derivatives are yet to be investigated in detail. In the current study, a chemical library was created to assemble all chemical information related to naturally occurring coumarins from the literature. Additionally, a multi-stage virtual screening combining QSAR modeling, molecular docking, and ADMET prediction was conducted against monoamine oxidase B and acetylcholinesterase, two relevant targets known for their neuroprotective properties and 'disease-modifying' potential in Parkinson's and Alzheimer's disease. Our findings revealed ten coumarin derivatives that may act as dual-target drugs against MAO-B and AChE. Two coumarin candidates were selected from the molecular docking study: CDB0738 and CDB0046 displayed favorable interactions for both proteins as well as suitable ADMET profiles. The stability of the selected coumarins was assessed through 100 ns molecular dynamics simulations which revealed promising stability through key molecular interactions for CDB0738 to act as dual inhibitor of MAO-B and AChE. However, experimental studies are necessary to evaluate the bioactivity of the proposed candidate. The current results may generate an increasing interest in bioprospecting naturally occurring coumarins as potential candidates against relevant macromolecular targets by encouraging virtual screening studies against our chemical library.Communicated by Ramaswamy H. Sarma.

Constituents of Stachys plants as potential dual inhibitors of AChE and NMDAR for the treatment of Alzheimer's disease: a molecular docking and dynamic simulation study.

Alzheimer's disease (AD) is a chronic neurodegenerative condition characterized by progressive cognitive impairment. While the formation of ß-amyloid plaques and neurofibrillary tangles are the hallmarks features of AD, the downstream consequence of these byproducts is the disruption of the cholinergic and glutamatergic neural systems. Growing evidence for the existence of interplay between AChE and NMDARs has opened up new venues for the discovery of novel ligands endowed with anticholinesterase and NMDAR-blocking activity. Plants belonging to the stachys genus have been extensively explored for having a broad range of therapeutic applications and have been used traditionally for millennia, to treat various CNS-related disorders, which makes them the ideal source of novel therapeutics. The present study was designed to identify natural dual-target inhibitors for AChE and NMDAR deriving from stachys genus for their potential use in AD. Using molecular docking, drug-likeness-profiling, MD simulation and MMGBSA calculations, an in-house database of biomolecules pertaining to the stachys genus was shortlisted based on their binding affinity, overall stability and critical ADMET parameters. Pre- and post-MD analysis revealed that Isoorientin effectively binds to AChE and NMDAR with various vital interactions, exhibits a stable behavior with minor fluctuations relative to two clinical drugs used as positive control, and displays strong and consistent interactions that lasted for the majority of the simulation. Findings from this study have elucidated the rationale behind the traditional use of Stachys plants for the treatment of AD and could provide new impetus for the development of novel dual-target therapeutics for AD treatment.Communicated by Ramaswamy H. Sarma.

Antiarthritic activity of Physalis peruviana fruit extract via inhibition of inflammatory mediators: Integrated in vitro, in vivo and in silico study.

ETHNOPHARMACOLOGICAL RELEVANCE: P. peruviana fruit, native to Andean region, is cultivated worldwide for its adaptability to various soil natures and climatic conditions. It is increasingly consumed for its high nutritional profile and history of ethnomedical uses including treatment of arthritis. Little pharmacological evidences support this folk use except for previous in vitro study that reported significant inhibition of protein denaturation. AIM OF THE STUDY: The study aims at providing new in vivo evidence on antiarthritic activity of P. peruviana fruits in vivo that justifies its traditional use through mechanism-based experiment. MATERIAL AND METHODS: Inhibition of inflammatory mediators is considered one of the key treatments to alleviate painful symptoms of rheumatoid arthritis (RA). Anti-inflammatory activity was assessed against COX-1 and COX-2 activity in vitro. Serum TNFα, IL-1ß and IL-6 were traced using in vivo model of adjuvant-induced arthritis. Gross/inflammatory changes in rat paw, relative mass indices of spleen and liver were further investigated together with joint tissue histoarchitecture. Seven metabolites from different phytochemical classes, that were previously reported in P. peruviana fruit, were evaluated in silico against TNF-α target protein (PDB ID: 2AZ5) to assess their inhibitory effect. This was followed by assessment of their drug-likeness based on Lipinski's rule according to their physicochemical and pharmacokinetic properties. RESULTS: High dose of extract (E-1000 mg) improved adjuvant-induced cachexia and attenuated immune-inflammatory responses in paw and serum parameters, with equipotent effect to MTX, in addition to minimal side effect profile on spleen and liver. Histopathological study of knee joint tissues confirmed dose-dependent improvement in arthritic groups treated with P. peruviana fruit extracts. The insilico study recommended steroidal lactones withaperuvin E/C and hydroxywithanolide E as promising lead compounds for inhibiting TNF enzyme as evidenced by docking scores of 6.301, 5.488 and 5.763 kcal/mol, respectively, fitting as well the Lipinski's rule of drug likeness. CONCLUSION: The study provided novel approach that rationalize folk use of P. peruviana fruit in treatment of arthritis.

Comprehensive phytochemical characterization of Persea americana Mill. fruit via UPLC/HR-ESI-MS/MS and anti-arthritic evaluation using adjuvant-induced arthritis model.

Persea americana Mill. (avocado fruit) has many health benefits when added to our diet due to various pharmacological activities, such as preventing bone loss and inflammation, modulating immune response and acting as an antioxidant. In the current study, the total ethanol extract (TEE) of the fruit was investigated for in vitro antioxidant and anti-inflammatory activity via DPPH and cyclooxygenase enzyme inhibition. Biological evaluation of the antiarthritic effect of the fruit extract was further investigated in vivo using Complete Freund's Adjuvant (CFA) arthritis model, where the average percentages of body weight change, inhibition of paw edema, basal paw diameter/weight and spleen index were estimated for all animal groups. Inflammatory mediators such as serum IL-6 and TNF-α were also determined, in addition to histopathological examination of the dissected limbs isolated from all experimental animals. Eighty-one metabolites belonging to different chemical classes were detected in the TEE of P. americana fruit via UPLC/HR-ESI-MS/MS. Two classes of lyso-glycerophospholipids; lyso-glycerophosphoethanolamines and lysoglycerophosphocholines were detected for the first time in avocado fruit in the positive mode. The TEE of fruit exhibited significant antioxidant and anti-inflammatory activity in vitro. In vivo anti-arthritic activity of the fruit TEE improved paw parameters, inflammatory mediators and spleen index. Histopathological findings showed marked improvements in the arthritic condition of the excised limbs. Therefore, avocado fruit could be proposed to be a powerful antioxidant and antiarthritic natural product.

Identification of novel dual acting ligands targeting the adenosine A2A and serotonin 5-HT1A receptors.

GPCRs are a family of transmembrane receptors that are profoundly linked to various neurological disorders, among which is Parkinson's disease (PD). PD is the second most ubiquitous neurological disorder after Alzheimer's disease, characterized by the depletion of dopamine in the central nervous system due to the impairment of dopaminergic neurons, leading to involuntary movements or dyskinesia. The current standard of care for PD is Levodopa, a dopamine precursor, yet the chronic use of this agent can exacerbate motor symptoms. Recent studies have investigated the effects of combining A2AR antagonist and 5-HT1A agonist on dyskinesia and motor complications in animal models of PD. It has been proved that the drug combination has significantly improved involuntary movements while maintaining motor activity, highlighting as a result new lines of therapy for PD treatments, through the regulation of both receptors. Using a combination of ligand-based pharmacophore modelling, virtual screening, and molecular dynamics simulation, this study intends on identifying potential dual-target compounds from IBScreen. Results showed that the selected models displayed good enrichment metrics with a near perfect receiver operator characteristic (ROC) and Area under the accumulation curve (AUAC) values, signifying that the models are both specific and sensitive. Molecular docking and ADMET analysis revealed that STOCK2N-00171 could be potentially active against A2AR and 5-HT1A. Post-MD analysis confirmed that the ligand exhibits a stable behavior throughout the simulation while maintaining crucial interactions. These results imply that STOCK2N-00171 can serve as a blueprint for the design of novel and effective dual-acting ligands targeting A2AR and 5-HT1A.Communicated by Ramaswamy H. Sarma.

Exploring natural products as multi-target-directed drugs for Parkinson's disease: an in-silico approach integrating QSAR, pharmacophore modeling, and molecular dynamics simulations.

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the midbrain. Current treatments provide limited symptomatic relief without halting disease progression. A multi-targeting approach has shown potential benefits in treating neurodegenerative diseases. In this study, we employed in silico approaches to explore the COCONUT natural products database and identify novel drug candidates with multi-target potential against relevant Parkinson's disease targets. QSAR models were developed to screen for potential bioactive molecules, followed by a hybrid virtual screening approach involving pharmacophore modeling and molecular docking against MAO-B, AA2AR, and NMDAR. ADME evaluation was performed to assess drug-like properties. Our findings revealed 22 candidates that exhibited the desired pharmacophoric features. Particularly, two compounds: CNP0121426 and CNP0242698 exhibited remarkable binding affinities, with energies lower than -10 kcal/mol and promising interaction profiles with the chosen targets. Furthermore, all the ligands displayed desirable pharmacokinetic properties for brain-targeted drugs. Lastly, molecular dynamics simulations were conducted on the lead candidates, belonging to the dihydrochalcone and curcuminoid class, to evaluate their stability over a 100 ns timeframe and compare their dynamics with reference complexes. Our findings revealed the curcuminoid CNP0242698 to have an overall better stability with the three targets compared to the dihydrochalcone, despite the high ligand RMSD, the curcuminoid CNP0242698 showed better protein stability, implying ligand exploration of different orientations. Similarly, AA2AR exhibited higher stability with CNP0242698 compared to the reference complex, despite the high initial ligand RMSD due to the bulkier active site. In NMDAR, CNP0242698 displayed good stability and less fluctuations implying a more restricted conformation within the smaller active site of NMDAR. These results may serve as lead compounds for the development and optimization of natural products as multi-target disease-modifying natural remedies for Parkinson's disease patients. However, experimental assays remain necessary to validate these findings.Communicated by Ramaswamy H. Sarma.

Probing the molecular mechanisms of α-synuclein inhibitors unveils promising natural candidates through machine-learning QSAR, pharmacophore modeling, and molecular dynamics simulations.

Parkinson's disease is characterized by a multifactorial nature that is linked to different pathways. Among them, the abnormal deposition and accumulation of α-synuclein fibrils is considered a neuropathological hallmark of Parkinson's disease. Several synthetic and natural compounds have been tested for their potency to inhibit the aggregation of α-synuclein. However, the molecular mechanisms responsible for the potency of these drugs to further rationalize their development and optimization are yet to be determined. To enhance our understanding of the structural requirements necessary for modulating the aggregation of α-synuclein fibrils, we retrieved a large dataset of α-synuclein inhibitors with their reported potency from the ChEMBL database to explore their chemical space and to generate QSAR models for predicting new bioactive compounds. The best performing QSAR model was applied to the LOTUS natural products database to screen for potential α-synuclein inhibitors followed by a pharmacophore design using the representative compounds sampled from each cluster in the ChEMBL dataset. Five natural products were retained after molecular docking studies displaying a binding affinity of - 6.0 kcal/mol or lower. ADMET analysis revealed satisfactory properties and predicted that all the compounds can cross the blood-brain barrier and reach their target. Finally, molecular dynamics simulations demonstrated the superior stability of LTS0078917 compared to the clinical candidate, Anle138b. We found that LTS0078917 shows promise in stabilizing the α-synuclein monomer by specifically binding to its hairpin-like coil within the N-terminal region. Our dynamic analysis of the inhibitor-monomer complex revealed a tendency towards a more compact conformation, potentially reducing the likelihood of adopting an elongated structure that favors the formation and aggregation of pathological oligomers. These findings offer valuable insights for the development of novel α-synuclein inhibitors derived from natural sources.

Assessment of functional feeding groups (FFG) structure of aquatic insects in North- western Rif - Morocco.

The involvement of trait-based approaches is crucial for understanding spatial patterns, energy flow and matter transfer in running water systems, which requires consistent knowledge of the functional structures of aquatic communities, with the advantage of combining physical properties and behavioral mechanisms of food acquisition rather than the taxonomic group. The present study indicated how functional feeding groups may be used as a proxy for classical taxonomic evaluation, as well as the potential interest in incorporating them as indicators of anthropogenic stressors. The composition and abundance of the functional feeding groups of aquatic insects were examined from September 2021 to August 2022 along the Western Rif Region. Benthic samples were collected from nine sampling points in the studied area using a Surber sampler with a mesh size of 500 µm and a diameter of 20*20 cm. The stations included in this work were chosen for their accessibility as well as their position on the hydrographic systems. The abundance of sampled aquatic organisms in the whole study area revealed 5,342 individuals belonging to 60 families and seven orders of aquatic insects, classified into five feeding functional groups. In terms of abundance, Collector-gatherers (Ephemeroptera and Diptera) were the most abundant trophic group at most of the sites, with a proportion of 38.47%. Predators (Coleoptera, Hemiptera and Odonata) were the second group at all sites, followed by Collector-filters, accounting for 39.53%, 28.14% and 22.37% respectively, while Scarpers and Shredders had the lowest representation across all sites with 4.16%. The high number of registered Collectors could be related to their ability to feed on a diverse range of food items compared to the remaining trophic guilds. According to the Canonical Correspondence Analysis results, physicochemical (i.e. T, pH, BOD5, Cl- and NO3-) and hydromorphological (i.e. current velocity and depth) variables were amongst the key predictors of shaping the functional structure of aquatic biota during this investigation. It is highly recommended to carry out suitable measures to largely attenuate anthropogenic pressures in order to preserve the integrity of freshwater bodies and their biota.

FETAL DOSE ESTIMATION DURING PREGNANCY USING GATE MONTE CARLO SIMULATION: APPLICATION OF HODGKIN'S LYMPHOMA RADIOTHERAPY.

The aim of this study is to estimate the fetal radiation dose for a pregnant patient treated for Hodgkin's lymphoma. Due to the supradiaphragmatic extensions, two plans are used for this treatment, one for supra-clavicular and the other for cervical lymph nodes, with beam energies of 18 and 6 MV, respectively. We model the ELEKTA accelerator (Versa HD Ltd, Crawly, UK) and the pregnant patient using GATE code. The accelerator is modelled based on the vendor-supplied data and the pregnant patient is modeled with a voxelized pregnant woman phantom (Katja, 29 years old) at the 24th week of pregnancy. In each plan, we estimate the absorbed dose of each fetus organ by delivering a 2 Gy for one fraction and then multiplying the result by 15 fractions to get the total prescribed dose, then we calculate the mean fetal absorbed dose. The results indicate that the mean absorbed fetal dose was 26.18 mGy.

Structural exploration of selected C6 and C7-substituted coumarin isomers as selective MAO-B inhibitors.

Monoamine Oxidase B is considered a successful target for developing antiparkinsonian drugs. Due to the side effects of current MAO-B inhibitors, there's an urgent need for novel potent and highly selective MAO-B inhibitors. A recent study has shown that coumarins tend to be more selective towards MAO-B than MAO-A when connected to a hex-5-ynyloxy chain at position 6 in contrast to their C7-isomers. The present study describes the mode of interaction of the C6 and C7-substituted coumarin isomers characterized by their difference in selectivity towards MAO-B through molecular docking and molecular dynamics simulations in an effort to elucidate the structural components and molecular interactions that may be responsible for MAO-B selectivity. Three isomeric coumarin pairs connected to ether chain at position 6 or 7 were taken from the literature and modelled according to their IUPAC nomenclature. Molecular docking study revealed one π- π stacking interaction with Tyr-326 in common between the selective coumarin C6-isomers. Resulting complexes of one isomeric coumarin pair that displayed the highest selectivity shift towards MAO-B were subject to 100 ns molecular dynamics simulations study to analyze the stability of the docked complexes. Molecular dynamics revealed that the C7-isomer is relatively stable in both MAO isoforms through the simulation duration, whereas the C6-isomer deemed unstable for MAO-A which may be due to the bulky Phe-208 residue in MAO-A. Our results might be applied for further development and optimization of coumarin derivatives into a successful drug against Parkinson's disease.Communicated by Ramaswamy H. Sarma.

A New Class of Cluster-Matrix Nanocomposite Made of Fully Miscible Components.

Nanocomposite materials, consisting of two or more phases, at least one of which has a nanoscale dimension, play a distinctive role in materials science because of the multiple possibilities for tailoring their structural properties and, consequently, their functionalities. In addition to the challenges of controlling the size, size distribution, and volume fraction of nanometer phases, thermodynamic stability conditions limit the choice of constituent materials. This study goes beyond this limitation by showing the possibility of achieving nanocomposites from a bimetallic system, which exhibits complete miscibility under equilibrium conditions. A series of nanocomposite samples with different compositions are synthesized by the co-deposition of 2000-atom Ni-clusters and a flux of Cu-atoms using a novel cluster ion beam deposition system. The retention of the metastable nanostructure is ascertained from atom probe tomography (APT), magnetometry, and magnetotransport studies. APT confirms the presence of nanoscale regions with ≈100 at% Ni. Magnetometry and magnetotransport studies reveal superparamagnetic behavior and magnetoresistance stemming from the single-domain ferromagnetic Ni-clusters embedded in the Cu-matrix. Essentially, the magnetic properties of the nanocomposites can be tailored by the precise control of the Ni concentration. The initial results offer a promising direction for future research on nanocomposites consisting of fully miscible elements.

Innovative Processing Technologies to Develop a New Segment of Functional Citrus-Based Beverages: Current and Future Trends.

The food industries are interested in developing functional products due to their popularity within nutritional and healthy circles. Functional fruit-based beverages represent one of the fast-growing markets due to the high concentrations of bioactive compounds (BCs), which can be health promoters. Hence, functional beverages based on citrus fruits are a potential way to take advantage of their nutritional and bioactive properties that could attract the interest of consumers. In order to ensure microbial and quality stability, the beverages are subjected to preservation treatment; however, the application of high temperatures leads to the loss of thermolabile BCs. Nowadays, innovative processing technologies (IPT) such as pulsed electric field (PEF), high-pressure processing (HPP), ultrasound processing (US), ohmic heating (OH), and microwave (MW) are a promising alternative due to their efficiency and low impact on juice BCs. The available literature concerning the effects of these technologies in functional fruit-based beverages is scarce; thus, this review gathers the most relevant information about the main positive and negative aspects of the IPT in functional properties, safety, and consumer acceptance of functional citrus-based beverages, as well as the use of citrus by-products to promote the circular economy in citrus processing.

In silico studies of natural product-like caffeine derivatives as potential MAO-B inhibitors/AA2AR antagonists for the treatment of Parkinson's disease.

Parkinson's disease is considered the second most frequent neurodegenerative disease. It is described by the loss of dopaminergic neurons in the mid-brain. For many decades, L-DOPA has been considered as the gold standard for treating Parkinson's disease motor symptoms, however, due to the decrease of efficacy, in the long run, there is an urgent need for novel antiparkinsonian drugs. Caffeine derivatives have been reported several times for their neuroprotective properties and dual blockade of monoamine oxidase (MAO) and adenosine A2A receptors (AA2AR). Natural products are currently attracting more focus due to structural diversity and safety in contrast to synthetic drugs. In the present work, computational studies were conducted on natural product-like caffeine derivatives to search for novel potent candidates acting as dual MAO-B inhibitors/AA2AR antagonists for Parkinson's disease. Our findings revealed two natural products among the top hits: CNP0202316 and CNP0365210 fulfill the requirements of drugs acting on the brain. The selected lead compounds were further studied using molecular dynamics simulation to assess their stability with MAO-B. Current findings might shift the interest towards natural-based compounds and could be exploited to further optimize caffeine derivatives into a successful dual-target-directed drug for managing and halting the neuronal damage in Parkinson's disease patients.

Dynamics of the Gut Bacteriome During a Laboratory Adaptation Process of the Mediterranean Fruit Fly, Ceratitis capitata.

Laboratory adaptation process used in sterile insect technique (SIT) programs can exert a significant impact on the insect-gut microbiome relationship, which may negatively impact the quality and performance of the fly. In the present study, changes in the gut microbiota that occur through laboratory adaptation of two Ceratitis capitata populations were investigated: Vienna 8 genetic sexing strain (GSS), a long-established control line, and a wild population recently introduced to laboratory conditions. The bacterial profiles were studied for both strains using amplicon sequencing of the 16S rRNA V3-V4 hypervariable region in larvae and in the gastrointestinal tract of teneral (1 day) and adults (5 and 15 days) reared under laboratory conditions for 14 generations (F0-F13). Findings demonstrated the development of distinct bacterial communities across the generations with differences in the bacterial composition, suggesting a strong impact of laboratory adaptation on the fly bacteriome. Moreover, different bacterial profiles were observed between wild and Vienna 8 FD-GSS displaying different patterns between the developmental stages. Proteobacteria, mainly members of the Enterobacteriaceae family, represented the major component of the bacterial community followed by Firmicutes (mainly in Vienna 8 FD-GSS adults) and Chlamydiae. The distribution of these communities is dynamic across the generations and seems to be strain- and age-specific. In the Vienna 8 FD-GSS population, Providencia exhibited high relative abundance in the first three generations and decreased significantly later, while Klebsiella was relatively stable. In the wild population, Klebsiella was dominant across most of the generations, indicating that the wild population was more resistant to artificial rearing conditions compared with the Vienna 8 FD-GSS colony. Analysis of the core bacteriome revealed the presence of nine shared taxa between most of the examined medfly samples including Klebsiella, Providencia, Pantoea, and Pseudomonas. In addition, the operational taxonomic unit co-occurrence and mutual exclusion networks of the wild population indicated that most of the interactions were classified as co-presence, while in the Vienna 8 FD-GSS population, the number of mutual exclusions and co-presence interactions was equally distributed. Obtained results provided a thorough study of the dynamics of gut-associated bacteria during the laboratory adaptation of different Ceratitis capitata populations, serving as guidance for the design of colonization protocols, improving the effectiveness of artificial rearing and the SIT application.

Development of Lepidium sativum Extracts/PVA Electrospun Nanofibers as Wound Healing Dressing.

Lepidium sativum L. (Garden cress/Hab El Rashad) (Ls), family Brassicaceae, has considerable importance in traditional medicine worldwide because of its antioxidant and anti-inflammatory activities. Ls fruits were used in Ayurvedic medicines as a useful drug for injuries, skin, and eye diseases. The aim of this study was to examine the effectiveness of the total ethanol extract (TEE) and polysaccharide (Poly) of Ls seeds loaded on poly(vinyl alcohol) (PVA) nanofibers (NFs) as a wound healing dressing and to correlate the activity with the constituents of each. TEE and Poly were phytochemically analyzed qualitatively and quantitatively. Qualitative analysis proved the presence of phenolic acids, flavonoids, tannins, sterols, triterpenes, and mucilage. Meanwhile, quantitative determinations were carried out spectrophotometrically for total phenolic and total flavonoid contents. High-performance liquid chromatography (HPLC) for TEE identified 15 phenolic acids and flavonoid compounds, with gallic acid and catechin as the majors. Separation, purification, and identification of the major compounds were achieved through a Puriflash system, column Sephadex LH20, and spectroscopic data (1H, 13C NMR, and UV). Eight compounds (gallic acid, catechin, rutin, kaempferol-3-O-rutinoside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, quercetin, and kaempferol) were obtained. Gas-liquid chromatography (GLC) analysis for Poly identified 11 compounds, with galactose being the main. The antioxidant activity for both extracts was measured by three different methods based on different mechanisms: 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP), and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). TEE has the highest effectiveness as an antioxidant agent with IC50 82.6 ± 8.35 µg/mL for DPPH and 772.47 and 758.92 µM Trolox equivalent/mg extract for FRAP and ABTS, respectively. The PVA nanofibers (NFs) for each sample were fabricated by electrospinning. The fabricated NFs were characterized by SEM and Fourier transform infrared spectroscopy (FTIR); the results revealed successful encapsulation of TEE and Poly in the prepared NFs. Moreover, the swelling index of TEE in the prepared NFs shows that it is the most appropriate for use as a wound dressing. Cytotoxicity studies indicated a high cell viability with IC50 216 µg/mL and 1750 µg/mL for TEE and Poly, respectively. Moreover, the results revealed that nanofibers possess higher cell viability compared to solutions with the same sample quantities: 9-folds for TEE and 4-folds for Poly of amount 400 µg. The in vitro wound healing test showed that the TEE nanofibers performed better than Poly nanofibers in accelerating wound healing, with 90% for TEE, more than that for the Poly extract (82%), after 48 h. These findings implied that the incorporation of TEE in PVA nanofibers was more efficient than incorporation of Poly in improving the biological activity in wound healing. In conclusion, the TEE and polysaccharides of L. sativum L seed are ideal candidates for nanofibrous wound dressings. Furthermore, the contents of phenolic acids and flavonoids in TEE, which have potential antioxidant activity, make the TEE of L. sativum more favorable for wound healing dressing.

Molecular docking study and molecular dynamic simulation of human cyclooxygenase-2 (COX-2) with selected eutypoids.

Inflammation is a key factor linked to almost all chronic and degenerative diseases implicit with certain levels of pain. In studies, over the past few years, it has been discovered that prostaglandins are the main cause of this inflammation and therefore could be blocked. Although no steroidal medications can be effective, natural compounds may offer a safer and often an effective alternative treatment for pain relief, especially for long-term use. Hence to find out natural anti-inflammatory compounds, we have highlighted five important butenolides that are eutypoid A, B, C, D and E with structure similar to that of rofecoxib, by ADMET and druglikeness analysis, followed by molecular docking with human COX-2 enzyme. Molecular docking studies revealed the importance of hydrophobic and hydrophilic amino acid residues for the stability of the ligands and that eutypoids C and E are the best candidates for the synthetic drugs with binding energy of -10.39 kcal/mol and -9.87 kcal/mol, respectively. The resulting complexes were then subject to 50 ns molecular dynamics (MD) simulation studies with the GROMACS package to analyze the stability of docked protein-ligand complexes and to assess the fluctuation and conformational changes during protein-ligand interaction. From the RMSD, RMSF, number of hydrogen bonds, SASA, PCA and MM/PBSA binding free energy analysis, we have found that out of five selected compounds eutypoid E showed good binding free energy of -174.45 kJ/mol, which is also good in other structural analyses. This compound displayed excellent pharmacological and structural properties to be drug candidates.Communicated by Ramaswamy H. Sarma.

Modified Masquelet Technique Using Allogeneic Graft for a Gustilo-Anderson Type III-A Open Fracture of the Femur with an 8 cm Bone Defect.

The induced membrane technique was initially described by Masquelet et al. in 1986 as a treatment for tibia nonunion; then, it became one of the established methods in the management of bone defects. Several changes have been made to this technique and have been used in different contexts and different methodologies. We present the case of a 16-year-old girl admitted to our department for a polytrauma after a motorcycle accident. She presented a Gustilo III-A open fracture of the right femoral shaft with a large bone defect of 8 centimeters that we treated with a modified Masquelet technique. In the first stage, an Open Reduction and Internal Fixation of the fracture was made using a 4,5 mm Dynamic Compression Plate and a PMMA cement was inserted at the bone defect area. The second stage was done after 11 weeks, and the defect area was filled exclusively with bone allograft from a bone bank. Complete bony union was seen at 60 weeks of follow-up. After the removal of the implants by another surgeon, the patient presented an atraumatic fracture of the neoformed bone that we treated with intramedullary femoral nailing associated with a local autograft using reaming debris. A complete bony union was achieved after 12 weeks with a complete range of motion of the hip and knee. The stability given to the fracture is essential because it influences the quality of the induced membrane and Masquelet has recommended high initial fixation rigidity to promote incorporation of the graft. It is recommended to delay the second stage of this technique after 8 weeks, especially in femoral reconstruction, to optimize the quality of the induced membrane. Several studies used a modified induced membrane technique to recreate a traumatic large bone defect, and all of them used an autologous bone graft alone or an enriched bone graft. In this case, the use of allograft exclusively seems to be as successful as an autologous or enriched bone graft. Now, with the advent of bone banks, it is possible to get an unlimited amount of allograft, so additional research and large studies are necessary before giving recommendations.

Unveiling the Local Atomic Arrangements in the Shear Band Regions of Metallic Glass.

The prospective applications of metallic glasses are limited by their lack of ductility, attributed to shear banding inducing catastrophic failure. A concise depiction of the local atomic arrangement (local atomic packing and chemical short-range order), induced by shear banding, is quintessential to understand the deformation mechanism, however still not clear. An explicit view of the complex interplay of local atomic structure and chemical environment is presented by mapping the atomic arrangements in shear bands (SBs) and in their vicinity in a deformed Vitreloy 105 metallic glass, using the scanning electron diffraction pair distribution function and atom probe tomography. The results experimentally prove that plastic deformation causes a reduction of geometrically favored polyhedral motifs. Localized motifs variations and antisymmetric (bond and chemical) segregation extend for several hundred nanometers from the SB, forming the shear band affected zones. Moreover, the variations within the SB are found both perpendicular and parallel to the SB plane, also observable in the oxidation activity. The knowledge of the structural-chemical changes provides a deeper understanding of the plastic deformation of metallic glasses especially for their functional applications and future improvements.

Magnetoelectric Tuning of Pinning-Type Permanent Magnets through Atomic-Scale Engineering of Grain Boundaries.

Pinning-type magnets with high coercivity at high temperatures are at the core of thriving clean-energy technologies. Among these, Sm2 Co17 -based magnets are excellent candidates owing to their high-temperature stability. However, despite intensive efforts to optimize the intragranular microstructure, the coercivity currently only reaches 20-30% of the theoretical limits. Here, the roles of the grain-interior nanostructure and the grain boundaries in controlling coercivity are disentangled by an emerging magnetoelectric approach. Through hydrogen charging/discharging by applying voltages of only ≈1 V, the coercivity is reversibly tuned by an unprecedented value of ≈1.3 T. In situ magneto-structural characterization and atomic-scale tracking of hydrogen atoms reveal that the segregation of hydrogen atoms at the grain boundaries, rather than the change of the crystal structure, dominates the reversible and substantial change of coercivity. Hydrogen reduces the local magnetocrystalline anisotropy and facilitates the magnetization reversal starting from the grain boundaries. This study opens a way to achieve the giant magnetoelectric effect in permanent magnets by engineering grain boundaries with hydrogen atoms. Furthermore, it reveals the so far neglected critical role of grain boundaries in the conventional magnetization-switching paradigm of pinning-type magnets, suggesting a critical reconsideration of engineering strategies to overcome the coercivity limits.