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On 31 December 2019, health authorities in the People's Republic of China informed the World Health Organization of a then limited outbreak of interstitial viral pneumonia, identified at a laboratory in the city of Wuhan. In mid-April 2020 this outbreak of COVID-19 (as the disease has been called) has aggravated and spread worldwide, causing more than 200,000 deaths and affecting especially the United States, Spain, Italy, France and the United Kingdom. Despite the severity of the outbreak, the pathological findings have not been described in detail and there are very few guidelines or protocols for conducting autopsy studies on patients who have died from COVID-19. There are currently very few histopathological case series studies on this disease. In addition, some of these studies have been performed on biopsies or surgical resection pieces from patients in whom disease was subsequently demonstrated or through minimally invasive autopsy protocols. None of the studies offer a detailed necropsy protocol. This document proposes a protocol of action for the institutes of Forensic Medicine facing the current SARS-CoV2 pandemic, which combines protection of worker safety with optimization of tissue collection.The increasing concern on the harmful effects caused by mineral oil-based lubricants towards the environment has given impetus to the evolution of green-lubricants. Vegetable oils are highly biodegradable, renewable, and possesses good lubricating property. In the present study Pongamia pinnata, non-edible vegetable oil, also known as Karanja Oil (KO) was used as the base oil for a lubricant. The preliminary properties, such as fatty acid profile and viscosity, which has a vital role in governing the performance of lubricants were evaluated experimentally as per international standards. The shear viscosity of KO which constitutes 8 major fatty acids were predicted using non-equilibrium molecular dynamics (NEMD) and periodic perturbation (PP) method using Optimised Potentials for Liquid Simulations (OPLS) and Generalized Amber Force Field (GAFF). The shear viscosities were evaluated at temperatures ranging from 313K to 373 K and pressure P = 0.1 MPa. The experimental and simulation data of KO shear viscosity are in line with each other using OPLS. The kinematic viscosities were calculated using the shear viscosities and densities obtained from simulation. The variation between experimental and simulation data is less while using OPLS, while GAFF force fields resulted in higher deviations.Neutrophils synthesize four immune associated serine proteases Cathepsin G (CTSG), Elastase (ELANE), Proteinase 3 (PRTN3) and Neutrophil Serine Protease 4 (NSP4). While previously considered to be immune modulators, overexpression of neutrophil serine proteases correlates with various disease conditions. Therefore, identifying novel small molecules that can potentially control or inhibit the proteolytic activity of these proteases is crucial to revert or temper the aggravated disease phenotype. To the best of our knowledge, although there is limited data for inhibitors of other neutrophil protease members, there is no previous clinical study of a synthetic small molecule inhibitor targeting NSP4. In this study, an integrated molecular modeling algorithm was performed within a virtual drug repurposing study to identify novel inhibitors for NSP4, using clinically approved and investigation drugs library (∼8000 compounds). Based on our rigorous filtration, we found that following molecules Becatecarin, Iogulamide, Delprostenate and Iralukast are predicted to block the activity of NSP4 by interacting with core catalytic residues. The selected ligands were energetically more favorable compared to the reference molecule. The result of this study identifies promising molecules as potential lead candidates.Growing concern about the difficulty in diagnosis and treatments of drug-resistant tuberculosis falls under the major global health issues. There is an urgent need for finding novel strategies to develop drugs or bioactive molecules against the global threat of Mycobacterium tuberculosis (MTB). Isoniazid (INH) is a front line drug against tuberculosis; it primarily targets the enoyl-acyl carrier protein reductase (InhA), a potent drug target in the mycolic acid pathway of MTB. To gain deeper insight into the impact of INH resistant mutation and its influence on the structural dynamics of InhA, combined conformational dynamics and residue interaction network (RIN) studies were performed. The molecular dynamics investigation provided a hint about the structural changes altering protein activity. The principal component analysis (PCA) based free energy landscape plot highlighted the highest stable part of wild-type (WT) and mutant structures. Intriguingly, the mutation at the 78th position of InhA from its native residue valine to alanine increases the structural stability with higher NADH binding affinity. The MM-PBSA based binding energy calculations confirm that electrostatic interactions played a critical role in the binding of NADH at the binding site of InhA. The calculated binding energy score, as well as potential hydrogen bonds and salt bridge networks, proved the strong binding of mutant InhA as compared to WT. Further, the mutation potentially altered the protein network topology, thereby subsequently affected the landscape of NADH binding. The present study is an attempt to understand the structural and functional impact associated with a drug-resistant mutation (V78A) thus it will be helpful in designing potent inhibitors against drug-resistant tuberculosis.Given the importance of food safety, it is highly desirable to develop a convenient, low-cost, and practical sensor for organophosphorus pesticides (OPs) detection. Here, a fluorescent paper analytical device (FPAD) based on aggregation-induced emission (AIE) nanoparticles (PTDNPs-0.10) and two-dimension MnO2 nanoflakes (2D-MnNFs) was developed for instrument-free and naked-eye analysis of OPs. PTDNP-MnNFs composites were obtained through 2D-MnNFs and PTDNPs-0.10 by electrostatic interaction and the fluorescence emission of PTDNPs-0.10 was quenched through fluorescence resonance energy transfer (FRET). When acetylcholinesterase (AChE) was present, acetylthiocholine (ATCh) was catalytically hydrolyzed into thiocholine, which reduced MnO2 of PTDNP-MnNFs into Mn2+, subsequently blocking the FRET and enhancing the fluorescence. Upon the addition of OP, AChE activity was depressed and thus the FRET between 2D-MnNFs and PTDNPs-0.10 was not affected, resulting in a slight change in fluorescence. On the basis of the variation in fluorescence intensity, highly sensitive detection of OP was readily achieved with a detection limit of 0.027 ng/mL; on the basis of the variation in brightness of FPAD, instrument-free and visual detection of OP was realized using a smartphone with a detection limit of 0.73 ng/mL. The application of FPAD has significantly simplified the detection procedure and decreased the test cost, supplying a new approach for on-site detection of OPs.The photothermal biosensing principle is of increasing interest for point-of-care detection, but has rarely been applied in portable analytical devices in a lab-on-a-chip format. Herein, a photothermally responsive poly (methyl methacrylate) (PMMA)/paper hybrid disk (PT-Disk) was developed as a novel photothermal immunoassay device with the integration of a clip-magazine-assembled photothermal biosensing strategy. The PT-Disk consisted of a dissociative thermoresponsive hydrogel-loaded clip unit where the sandwich-type immunoreaction with an iron oxide-to-Prussian blue nanoparticle (PB NP) conversion took place and a magazine bearer for the rotational clip assembly and visual signal outputs. Upon laser irradiation of the clip-magazine-assembled PT-Disk, on-chip photothermal effect of PB NPs triggered both dose-dependent temperature elevation and the subsequent release of dye solutions from the central clip unit to surrounding magazine-bearing paper channels as the result of phase transition of the hydrogels, realizing multiplexed thermal image- and distance-based visual quantitative signal outputs in combination with the preliminary colorimetric readout on the PT-Disk. Using the multiplexed tri-mode signal outputs, the PT-Disk can quantify prostate specific antigen with limits of detection of 1.4-2.8 ng mL-1. This is the first attempt to apply the photothermal biosensing principle in portable PMMA/paper-based analytical devices, which offers not only versatile on-chip visual quantitative signal outputs, but also the implementation of the photothermal biosensing principle in a lab-on-a-chip format.Cancer cell enumeration and phenotyping can predict the prognosis and the therapy efficacy in patients, yet it remains challenging to detect the rare tumor cells. Herein, we report an octopus-inspired, bifunctional aptamer signal amplifier-based cytosensor (OApt-cytosensor) for sensitive cell analysis. By assembling high-affinity antibodies on an electrode surface, the target cells could be specifically captured and thus been sandwiched by the cell surface marker-specific DNA aptamers. These on-cell aptamers function as electrochemical signal amplifiers by base-selective electronic doping with methylene blue. Such a sandwich configuration enables highly sensitive cell detection down to 10 cells/mL (equal to ~1-2 cells at a sampling volume of 150 μL), even in a large excess of nontarget blood cells. This approach also reveals the cell-surface markers and tracks the cellular epithelial-to-mesenchymal transition induced by signaling regulators. Furthermore, the electron-doped aptamer shows remarkable cell fluorescent labeling that guides the release of the captured cells from electrode surface via electrochemistry. These features make OApt-cytosensor a promising tool in revealing the heterogeneous cancer cells and anticancer drug screening at the single-cell level.In recent years, imidacloprid and fipronil have been reported to harm beneficial insects, such as honey bees, and to potentially pose risks to mammals, including humans. Considering their widespread use and potential minimum toxic range from 10 ppb to 1 ppm (species dependent), a simple, rapid, sensitive, and reliable method for screening and detection is urgently needed. Here, we present a surface plasmon resonance (SPR)-based nanoplasmonic chip integrated with a multichannel spectral imaging system to detect ecosystem-harming pesticides. The pre-modification of the designed mercapto-haptens reduced detection time to 2.5 h. Moreover, owing to the multichannel configuration, it was possible to introduce an internal standard analytical method to effectively reduce matrix interference in real samples; thus, the concentration of the target pesticide could be determined more precisely. The strong linearity of the spiked sample test results indicated high accuracy in quantifying target pesticides. Considering the limit of detection (~10 ppb), the cutoffs for detection and quantification were set at 15 and 45 ppb, respectively, and were used as the detection criteria. The detection results of the blind tests of real samples were also compared with those of liquid chromatography electrospray ionization tandem mass spectrometry (standard method) and were highly consistent. find more The custom-made integrated SPR system allows much simpler, label-free, high-throughput, and reliable on-site identification and quantification of imidacloprid and fipronil. All test results validated the platform's capability in the on-site rapid screening and detection of pesticide residues at the parts per billion and parts per million levels.