Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors

Development of heat shock protein 90 (Hsp90) C‐terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti‐proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°.     

Dual-path handheld system for cornea and retina imaging using optical coherence tomography

Optical Review - A dual-path handheld system is proposed for cornea and retina imaging using spectral domain optical coherence tomography. The handheld sample arm is designed to acquire two images...     

Recyclable N-heterocyclic carbene/palladium catalyst on graphene oxide for the aqueous-phase Suzuki reaction

Graphene oxide (GO) was functionalized with a N-heterocyclic carbene (NHC) precursor, 3-(3-aminopropyl)-1-methylimidazolium bromide ([APMIm][Br]) for the immobilization of palladium catalyst. The GO-supported NHC precursor (IMGO) formed a stable complex with Pd(OAc)₂ (GO–NHC–Pd), which showed excellent catalytic activity and fast reaction kinetics in the aqueous-phase Suzuki reaction of aryl bromides and chlorides at relatively mild conditions (1 h at 50 °C). The GO–NHC–Pd catalyst was reused several times without any loss of its catalytic activity in the Suzuki reaction of aryl bromide.     

Experimental comparison of performance and emission characteristics of 4-stroke CI engine operated with Roselle and Jatropha biodiesel blends

The environmental degradation, combined with the continuous depletion of the world's fossil fuel reserves, has forced the search for alternative fuels. This study was performed to investigate the performance of novel biodiesels in the CI engine. The experiments were performed at three different compressions ratios (16:1, 17:1, 18:1) and four loading conditions (25%, 50%, 75%, 100%). Different types of fuels such as jatropha biodiesel (JB), roselle biodiesel (RB), and ternary biodiesel (TB) were prepared and analyzed. The thermal performance of different fuels was analyzed in terms of brake thermal efficiency (BTE), brake specific fuel consumption (BSFC), and exhaust gas temperature (EGT). The emission characteristics such as CO₂ emission, NO_x emission, and smoke emission were analyzed for all types of fuels. The results of these fuels in the engine were compared with mineral diesel (MD). The BTE was increased with increasing compression ratios and loads for all types of fuels. The BSFC was increased with increasing compression ratios but decreased with increasing loads. The increase in emission of NO_x was observed at higher compression ratios and loads. However, the CO₂ emission was decreased at higher loads and lower compression ratio. The performance curves achieved with a 20% jatropha biodiesel blend showed results that were approximate to those obtained with pure MD. The comparative analysis between different fuels showed that JB exhibit higher thermal performance as compared to other biodiesels. Therefore, JB can be a better alternative to conventional fuel.     

CT and MRI Medical Image Fusion Using Noise-Removal and Contrast Enhancement Scheme with Convolutional Neural Network

Medical image fusion (MIF) has received painstaking attention due to its diverse medical applications in response to accurately diagnosing clinical images. Numerous MIF methods have been proposed to date, but the fused image suffers from poor contrast, non-uniform illumination, noise presence, and improper fusion strategies, resulting in an inadequate sparse representation of significant features. This paper proposes the morphological preprocessing method to address the non-uniform illumination and noise by the bottom-hat–top-hat strategy. Then, grey-principal component analysis (grey-PCA) is used to transform RGB images into gray images that can preserve detailed features. After that, the local shift-invariant shearlet transform (LSIST) method decomposes the images into the low-pass (LP) and high-pass (HP) sub-bands, efficiently restoring all significant characteristics in various scales and directions. The HP sub-bands are fed to two branches of the Siamese convolutional neural network (CNN) by process of feature detection, initial segmentation, and consistency verification to effectively capture smooth edges, and textures. While the LP sub-bands are fused by employing local energy fusion using the averaging and selection mode to restore the energy information. The proposed method is validated by subjective and objective quality assessments. The subjective evaluation is conducted by a user case study in which twelve field specialists verified the superiority of the proposed method based on precise details, image contrast, noise in the fused image, and no loss of information. The supremacy of the proposed method is further justified by obtaining 0.6836 to 0.8794, 0.5234 to 0.6710, and 3.8501 to 8.7937 gain for QFAB, CRR, and AG and noise reduction from 0.3397 to 0.1209 over other methods for objective parameters.     

Caseinolytic Proteins (Clp) in the Genus Klebsiella: Special Focus on ClpK

Caseinolytic proteins (Clp), which are present in both prokaryotes and eukaryotes, play a major role in cell protein quality control and survival of bacteria in harsh environmental conditions. Recently, a member of this protein family, ClpK was identified in a pathogenic strain of Klebsiella pneumoniae which was responsible for nosocomial infections. ClpK is linked to the thermal stress survival of this pathogen. The genome wide analysis of Clp proteins in Klebsiella spp. indicates that ClpK is present in only 34% of the investigated strains. This suggests that the uptake of the clpk gene is selective and may only be taken up by a pathogen that needs to survive harsh environmental conditions. In silico analyses and molecular dynamic simulations show that ClpK is mainly α-helical and is highly dynamic. ClpK was successfully expressed and purified to homogeneity using affinity and anion exchange chromatography. Biophysical characterization of ClpK showed that it is predominantly alpha-helical, and this is in agreement with in silico analysis of the protein structure. Furthermore, the purified protein is biologically active and hydrolyses ATP in a concentration- dependent manner.     

Thiourea Derivatives,Simple in Structure but Efficient Enzyme Inhibitors and Mercury Sensors

In this study six unsymmetrical thiourea derivatives, 1-isobutyl-3-cyclohexylthiourea (1), 1-tert-butyl-3-cyclohexylthiourea (2), 1-(3-chlorophenyl)-3-cyclohexylthiourea (3), 1-(1,1-dibutyl)-3-phenylthiourea (4), 1-(2-chlorophenyl)-3-phenylthiourea (5) and 1-(4-chlorophenyl)-3-phenylthiourea (6) were obtained in the laboratory under aerobic conditions. Compounds 3 and 4 are crystalline and their structure was determined for their single crystal. Compounds 3 is monoclinic system with space group P2₁/n while compound 4 is trigonal, space group R³:H. Compounds (1–6) were tested for their anti-cholinesterase activity against acetylcholinesterase and butyrylcholinesterase (hereafter abbreviated as, AChE and BChE, respectively). Potentials (all compounds) as sensing probes for determination of deadly toxic metal (mercury) using spectrofluorimetric technique were also investigated. Compound 3 exhibited better enzyme inhibition IC₅₀ values of 50, and 60 µg/mL against AChE and BChE with docking score of −10.01, and −8.04 kJ/mol, respectively. The compound also showed moderate sensitivity during fluorescence studies.     

A Robust Wearable Point-of-Care CNT-Based Strain Sensor for Wirelessly Monitoring Throat-Related Illnesses

Point-of-care testing (POC) has the ability to detect chronic and infectious diseases early or at the time of occurrence and provide a state-of-the-art personalized healthcare system. Recently, wearable and flexible sensors have been employed to analyze sweat, glucose, blood, and human skin conditions. However, a flexible sensing system that allows for the real-time monitoring of throat-related illnesses, such as salivary parotid gland swelling caused by flu and mumps, is necessary. Here, for the first time, a wearable, highly flexible, and stretchable piezoresistive sensing patch based on carbon nanotubes (CNTs) is reported, which can record muscle expansion or relaxation in real-time, and thus act as a next-generation POC sensor. The patch offers an excellent gauge factor for in-plane stretching and spatial expansion with low hysteresis. The actual extent of muscle expansion is calculated and the gauge factor for applications entailing volumetric deformations is redefined. Additionally, a bluetooth-low-energy system that tracks muscle activity in real-time and transmits the output signals wirelessly to a smartphone app is utilized. Numerical calculations verify that the low stress and strain lead to excellent mechanical reliability and repeatability. Finally, a dummy muscle is inflated using a pneumatic-based actuator to demonstrate the application of the affixed wearable next-generation POC sensor.     

Fabrication of a <Emphasis Type="Italic">p</Emphasis>–<Emphasis Type="Italic">n</Emphasis> Heterojunction Using Topological Insulator Bi<Subscript>2</Subscript>Te<Subscript>3</Subscript>–Si and Its Annealing Response

A junction device has been fabricated by growing p-type Bi₂Te₃ topological insulator (TI) film on an n-type silicon (Si) substrate using a thermal evaporation technique. Annealing using different temperatures and durations was employed to improve the quality of the film, as confirmed by microstructural study using x-ray diffraction (XRD) analysis and atomic force microscopy (AFM). The p–n diode characteristics of the junction devices were studied, and the effect of annealing investigated. An improved diode characteristic with good rectification ratio (RR) was observed for devices annealed for longer duration. Reduction in the leakage or reverse saturation current (\( I_{\rm{R}} \)) was observed with increase in the annealing temperature. The forward-bias current (\( I_{\rm{F}} \)) dropped in devices annealed above 400°C. The best results were observed for the sample device annealed at 450°C for 3 h, showing figure of merit (FOM) of 0.621 with RR ≈ 504 and \( I_{\rm{R}} \) = 0.25 μA. In terms of ideality factor, the sample device annealed at 550°C for 2 h was found to be the best with \( n \) = 6.5, RR ≈ 52.4, \( I_{\rm{R}} \) = 0.61 μA, and FOM = 0.358. The majority-carrier density \( \left( {N_{\rm{A}} } \right) \) in the p-Bi₂Te₃ film of the heterojunction was found to be on the order of 10⁹/cm³ to 10¹¹/cm³, quite close to its intrinsic carrier concentration. These results are significant for fundamental understanding of device applications of TI materials as well as future applications in solar cells.