Reduction of elastic stress concentrations in end-milled keyed connections

Frozen-stress, three-dimensional models were used to study the elastic stress distribution in both metric and inch rectangular, parallel, standard keys, shafts and hubs with end-milled keyways, loaded in torsion. The coefficient of friction between the shaft and the hub was measured and the surface conditions were arranged to simulate typical prototype friction. Positions and magnitudes of the peak shear stresses were determined in the prismatic part and at the ends of keys and keyways. The axial position of torque application to the hub, the key length and key-end shape were altered to investigate their effects on the stress distributions. The maximum shear stresses in the shaft occur in the keyway end if the key is not chamfered. The maximum stress in the standard metric shaft is 25 percent greater than in the inch standard. Changing the axial position of torque application from the middle to the front increases the peak stresses by about 13 percent. Doubling the length of hub and key reduces the stresses by about 25 percent. Filing off parts of the key to prevent contact at the keyway end reduces the maximum stresses by 11 percent.     

Isolation and In Silico Anti-SARS-CoV-2 Papain-Like Protease Potentialities of Two Rare 2-Phenoxychromone Derivatives from Artemisia spp.

Two rare 2-phenoxychromone derivatives, 6-demethoxy-4`-O-capillarsine (1) and tenuflorin C (2), were isolated from the areal parts of Artemisia commutata and A. glauca, respectively, for the first time. Being rare in nature, the inhibition potentialities of 1 and 2 against SARS-CoV-2 was investigated using multistage in silico techniques. At first, molecular similarity and fingerprint studies were conducted for 1 and 2 against co-crystallized ligands of eight different COVID-19 enzymes. The carried-out studies indicated the similarity of 1 and 2 with TTT, the co-crystallized ligand of COVID-19 Papain-Like Protease (PLP), (PDB ID: 3E9S). Therefore, molecular docking studies of 1 and 2 against the PLP were carried out and revealed correct binding inside the active site exhibiting binding energies of −18.86 and −18.37 Kcal/mol, respectively. Further, in silico ADMET in addition to toxicity evaluation of 1 and 2 against seven models indicated the general safety and the likeness of 1 and 2 to be drugs. Lastly, to authenticate the binding and to investigate the thermodynamic characters, molecular dynamics (MD) simulation studies were conducted on 1 and PLP.     

Evaluation of the Anticancer Potential of Crude,Irradiated Cerastes cerastes Snake Venom and Propolis Ethanolic Extract & Related Biological Alterations

We aimed to evaluate the anticancer potential of crude venom (CV), γ irradiated Certastes cerastes venom (IRRV), and propolis ethanolic extract (PEE). IRRV showed a higher toxicity than CV, while CV-PEE showed higher toxicity than IRRV and CV against lung [A549] and prostate [PC3] cancer cells. Toxicity to [A549] and [PC3] cells was concentration and cell type dependent. In comparison to controls, apoptotic genes showed a significant upregulation of P53 and Casp-3 and a downregulation of Bcl-2. Also, induced elevated DNA accumulation in the [S] phase post PC3 cell treatment with IRRV and CV, as well as a significant DNA accumulation at G2/M phase after IRRV treatment of A549 cells. In contrast, PC3 cells showed a negligible cellular DNA accumulation after PEE treatment. Glutathione reductase [GR] was reduced in case of PC3 and A549 cell treated with IRRV, CV, and PEE compared with its values in untreated cell control. The Malondialdehyde [MDA] values in both cells recorded a significant elevation post IRRV treatment compared to the rest of the treatment regimen and untreated cell control. Similarly, IRRV and CV-PEE mix showed obviously higher reactive oxygen species [ROS] values than PC3 and A549 cell treatments with CV and PEE.     

Fluorescent gold nanoclusters as pH sensors for the pH 5 to 9 range and for imaging of blood cell pH values

Microchimica Acta - The authors describe the use of gold nanoclusters (AuNCs) with a diameter of ~2 nm for fluorescent sensing of pH values in the range from 5 to 9. The AuNCs were synthesized in...     

Mössbauer effect study of the effect of gamma irradiation and heat treatment on montmorillonite

Mössbauer spectroscopy was used to study the effect of gamma irradiation and heat treatment on montmorillonite. Samples were irradiated to gamma-ray doses ranging from 10 Gy up to 30 MGy. Other samples were heated to different temperatures from 400 C up to 1350 C. The lattice distortion caused by gamma irradiation could be followed. The phase transformations which occurred through and above the dehydroxilation temperature range could be traced and identified. The Mössbauer results were confirmed by X-ray diffraction results.     

New thieno[2,3-d]pyrimidine derivatives as EGFRWT and EGFRT790M inhibitors: Design,synthesis, antiproliferative activities,docking studies,ADMET, toxicity,MD simulation studies

A series of thieno[2,3-d]pyrimidines were designed and synthesized as epidermal growth factor receptor (EGFR) inhibitors. These compounds were tested for their ability to inhibit MCF-7 and A549 cancer cells. The most active compound, 12c , inhibited the growth of both cell lines, with IC₅₀ values of 15.67 and 12.16 μM, respectively. It was found that 12c had inhibitory effects on both EGFR^WT and EGFR^T790M isoforms, with inhibitory partialities of 37.50 and 148.90 nM, respectively. Additionally, 12c was found to be safer than erlotinib against normal cell lines (IC₅₀ = 38.61 μM). Compound 12c induced early and late apoptosis in A549 cells and arrested cell growth at G1 and G2/M phases. 12c was also found to increase caspases 3 and 8 ratios. Molecular docking indicated the correct binding modes of the synthesized compounds. MD simulations, MM-GBSA, and PLIP studies confirmed the precise binding of 12c to the EGFR protein over 100 ns.     

Ecofriendly chromatographic estimation of spasmolytic pharmaceutical mixture along with official toxic impurity, 3,5-dichloroaniline: Complete green profile appraisal

Nowadays, Green Analytical Chemistry is widely applied to provide various analytical methods with eco-friendly procedures employing the least toxic, harmful reagents on humans and the environment without affecting the efficacy of the determination. Accordingly, two eco-friendly, accurate, and reliable high-performance thin-layer chromatography-densitometry and high-performance liquid chromatographic methods were established for the determination and separation of two antispasmodic drugs, namely phloroglucinol and trimethylphloroglucinol in their pure, combined dosage form along with phloroglucinol toxic impurity, 3,5-dichloroaniline. For high-performance thin-layer chromatography-densitometry, efficient separation was developed via utilizing the stationary phase of high-performance thin-layer chromatography silica gel 60 F₂₅₄ plates and developing a system comprising of ethyl acetate-butanol-ammonia in the ratio of 8.0:2.0:0.2, by volume and scanning of the developed bands at 210.0 nm. The subsequent method is isocratic high-performance liquid chromatography with diode array detection in which separation was successively attained using XTerra RP-C₁₈ (250 × 4.6 mm, 5 μm) column as stationary phase and methanol-10.0 mM phosphate buffer, pH 3.7 ± 0.1 as mobile phase in the ratio of 75.0:25.0, v/v at flow rate 1.0 ml/min and scanning at 220.0 nm. The developed liquid chromatography methods were validated according to the International Council for Harmonization guidelines, and all results acknowledged their efficacy. Additionally, the proposed methods worked well for assessing the cited drugs in binary combined commercially available pharmaceutical formulation. The greenness profile of the present methods was assessed and estimated using various assessment tools, namely; Green Analytical Procedure Index, analytical eco-scale method, National Environmental Method Index in addition to Analytical GREEnness tool to evaluate the greenness of the provided methods with a statistical comparison between them to assess the more green ones.     

Synthesis and Antifungal Activity of Novel Quinazolin-4(3H)-one Derivatives

A novel group of 6-iodoquinazolin-4(3H)-one derivatives was prepared starting from 6-iodo-2-ethoxy-4H-3,1-benzoxazin-4-one (3) via action of various nitrogen nucleophiles such as primary and secondary amines, hydrazine hydrate, and its derivatives. The 3-amino-2-hydrazinyl-6-iodoquinazolin-4(3H)-one (15) was used as a key starting material to prepare new heterocyclic compounds. The structures of all synthesized compounds were inferred from the infrared, mass spectral, and ¹H NMR spectral data as well as elemental analysis. The fungicidal activities of the target compounds were preliminarily evaluated.     

Adsorption Study of Immunoglobulin G Subclasses from Different Species by Pseudobioaffinity Separation on Histidyl–Bisoxirane–Sepharose

Adsorption chromatography is increasingly used for protein separations and biomedical applications. Therapeutic molecules such as antibodies, cytokines, therapeutic DNA, and plasma proteins must be purified before characterization and utilization. Use of immunoglobulins as immunodiagnostic and therapeutic tools has initiated many attempts to develop new adsorbents for their separation. Protein A and protein G are the affinity ligands most widely used for separation of immunoglobulins. These proteins are reliable, and have good selectivity and specificity, but are very expensive. Much attention has therefore been devoted to developing alternative methods for separation of immunoglobulins. Pseudobiospecific ligands, for example metal ions and amino acids, can be used for separation of a wide range of biological molecules. In this study, IgG₁, IgG₂, and IgG₃, three subclasses of human IgG, were separated from human serum using the amino acid histidine grafted on to bisoxirane-activated Sepharose, as pseudobiospecific adsorbent. Adsorption of IgG from different animal species on the same chromatographic adsorbent was also tested. The high recovery and purification on histidyl–bisoxirane–Sepharose gel of IgG from all the sources tested compared well with results obtained by use of protein A–Sepharose gel.