Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors. Traditional inflammation and pain relief drugs target both cyclooxygenase 1 and 2 (COX-1 and COX-2), causing severe side effects. Here, the authors use in situ click chemistry to develop COX-2 specific inhibitors with high in vivo anti-inflammatory activity.

/pdf/in-situ-click-chemistry-generation-of-cyclooxygenase-2-zyy8rhnlnx.pdf

In situ click chemistry generation of cyclooxygenase-2 inhibitors

Single cell transcriptomics (scRNA-seq) has transformed our ability to discover and annotate cell types and states, but deep biological understanding requires more than a taxonomic listing of clusters. As new methods arise to measure distinct cellular modalities, including high-dimensional immunophenotypes, chromatin accessibility, and spatial positioning, a key analytical challenge is to integrate these datasets into a harmonized atlas that can be used to better understand cellular identity and function. Here, we develop a computational strategy to "anchor" diverse datasets together, enabling us to integrate and compare single cell measurements not only across scRNA-seq technologies, but different modalities as well. After demonstrating substantial improvement over existing methods for data integration, we anchor scRNA-seq experiments with scATAC-seq datasets to explore chromatin differences in closely related interneuron subsets, and project single cell protein measurements onto a human bone marrow atlas to annotate and characterize lymphocyte populations. Lastly, we demonstrate how anchoring can harmonize in-situ gene expression and scRNA-seq datasets, allowing for the transcriptome-wide imputation of spatial gene expression patterns, and the identification of spatial relationships between mapped cell types in the visual cortex. Our work presents a strategy for comprehensive integration of single cell data, including the assembly of harmonized references, and the transfer of information across datasets. Availability: Installation instructions, documentation, and tutorials are available at: https://www.satijalab.org/seurat

https://biorxiv.org/content/biorxiv/early/2018/11/02/460147.full-text.pdf

Comprehensive integration of single cell data

Isogenic strain construction and gene mapping in Candida albicans.

Microwave assisted synthesis – a critical technology overview

1 Review 1.1 Overview 1.2 Solid-phase organic synthesis (SPOS) 1.3 Beyond conventional solid-phase organic synthesis 1.4 The review 1.5 Some definitions 1.6 Solid-supported reagents and scavengers 1.7 Multi-step use of solid-supported reagents and scavenging reagents 1.8 Conclusions and future perspective 2 Introduction to the tables 2.1 Organisation of tables (reagent and catalyst section) 2.2 Representative data entry (reagent and catalyst section) 2.3 Organisation of tables (scavenging agents section) 2.4 Representative data entry (scavenging agents section) 3 Tables of reagents and catalysts 4 Tables of scavengers 5 Other relevant reviews 5.1 Insoluble polymers 5.1.1 Structure and physical properties (insoluble polymers) 5.1.2 General (insoluble polymers) 5.1.3 Reactions (insoluble polymers) 5.1.4 Miscellaneous (insoluble polymers) 5.2 Soluble polymers 5.2.1 General (soluble polymers) 5.2.2 Reactions (soluble polymers) 5.3 Inorganic solids 5.3.1 Structure and physical properties (inorganic solids) 5.3.2 General (inorganic solids) 5.3.3 Reactions (inorganic solids) 5.3.4 Miscellaneous (inorganic solids) 5.4 Miscellaneous supports 5.4.1 Structure and physical properties (miscellaneous supports) 5.4.2 General (miscellaneous supports) 5.4.3 Reactions (miscellaneous supports) 5.4.4 Miscellaneous (miscellaneous supports) 5.5 Purification strategies 5.5.1 Various supports (purification strategies) 5.5.2 Insoluble polymers (purification strategies) 6 Acknowledgements 7 Abbreviations 8 References 1 Review

Multi-step organic synthesis using solid-supported reagents and scavengers: a new paradigm in chemical library generation

Live-cell imaging with fluorescent probes is an essential tool in chemical biology to visualize the dynamics of biological processes in real-time. Intracellular disease biomarker imaging remains a formidable challenge due to the intrinsic limitations of conventional fluorescent probes and the complex nature of cells. This work reports the in cellulo assembly of a fluorescent probe to image cyclooxygenase-2 (COX-2). We developed celecoxib-azide derivative 14, possessing favorable biophysical properties and excellent COX-2 selectivity profile. In cellulo strain-promoted fluorogenic click chemistry of COX-2-engaged compound 14 with non/weakly-fluorescent compounds 11 and 17 formed fluorescent probes 15 and 18 for the detection of COX-2 in living cells. Competitive binding studies, biophysical, and comprehensive computational analyses were used to describe protein-ligand interactions. The reported new chemical toolbox enables precise visualization and tracking of COX-2 in live cells with superior sensitivity in the visible range.

In Cellulo Generation of Fluorescent Probes for Live-Cell Imaging of Cylooxygenase-2.

Crystalline thin films of Eu, Dy, and Er-doped CaWO4 and CaMoO4 of thicknesses 100–150 nm were synthesized by pulsed laser deposition on fused silica substrates. The atomic force and scanning electron microscopy studies confirm uniform and dense surface morphology of the samples. Tetragonal CaWO4 films show preferred growth of crystallites of (112) orientation. CaMoO4 shows texturing of crystallites of (004) orientation, while (112) crystallites are favored upon doping with rare earth ions. CaWO4 has a higher optical bandgap (5.0–5.2 eV) than CaMoO4 (3.6–4.4 eV), and both materials show blue light emission with stronger luminescence in molybdate samples. Eu doped CaWO4 and CaMoO4 produce red light emission, while Er-doped samples emit green light. The samples 1 mol.% Dy2O3–CaWO4 and 2 mol.% Eu2O3–5 mol.% Dy2O3–CaWO4 exhibit white light emission properties.

Rare earth doped CaWO4 and CaMoO4 thin films for white light emission

Cardiovascular complications are frequently observed in diabetic patients and are mostly caused by endothelial dysfunction associated with a decline in biosynthesis of nitric oxide (NO). In response to this concern, a remarkable increase in the interest for development of NO-releasing hybrid drugs has been observed. The NO-donating entity was linked to known drugs with the belief that NO is a vasorelaxant and an inhibitor of platelet aggregation or reduces thrombotic events. Many of these NO-releasing hybrid drugs have shown significant improvement in cardiovascular safety. In this editorial the potential roles of NO-releasing drugs for the treatment of cardiovascular complications in diabetes will be discussed.

Do nitric oxide-releasing drugs offer a potentially new paradigm for the management of cardiovascular risks in diabetes?

Coronavirus disease knocked in Wuhan city of China in December 2019 which spread quickly across the world and infected millions of people within a short span of time. COVID-19 is a fast-spreading contagious disease which is caused by SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2). Accurate time series forecasting modeling is the need of the hour to monitor and control the universality of COVID-19 effectively, which will help to take preventive measures to break the ongoing chain of infection. India is the second highly populated country in the world and in summer the temperature rises up to 50°, nowadays in many states have more than 40° temperatures. The present study deals with the development of the autoregressive integrated moving average (ARIMA) model to predict the trend of the number of COVID-19 infected people in most affected states of India and the effect of a rise in temperature on COVID-19 cases. Cumulative data of COVID-19 confirmed cases are taken for study which consists of 77 sample points ranging from 1st March 2020 to 16th May 2020 from six states of India namely Delhi (Capital of India), Madya Pradesh, Maharashtra, Punjab, Rajasthan, and Uttar Pradesh. The developed ARIMA model is further used to make 1-month ahead out of sample predictions for COVID-19. The performance of ARIMA models is estimated by comparing measures of errors for these six states which will help in understanding future trends of COVID-19 outbreak. Temperature rise shows slightly negatively correlated with the rise in daily cases. This study is noble to analyse the variation of COVID-19 cases with respect to temperature and make aware of the state governments and take precautionary measures to flatten the growth curve of confirmed cases of COVID-19 infections in other states of India, nearby countries as well.

/pdf/prediction-of-covid-19-pervasiveness-in-six-major-affected-i5cv31qadg.pdf

Prediction of COVID-19 pervasiveness in six major affected states of India and two-stage variation with temperature.

Recent experimental evidence demonstrated an aberrant overexpression of cyclooxygenase-1 (COX-1) in various cancers, which has stimulated the development of COX-1-selective inhibitors as promising anticancer drugs and cancer imaging agents. Herein we describe the synthesis and validation of 3-(furan-2-yl)-N-aryl 5-amino-pyrazoles as a novel class of COX-1 inhibitors, including molecular docking studies. Among all tested compounds, 4-(5-azido-3-(furan-2-yl)-1H-pyrazol-1-yl)benzoic 17 displayed a favorable COX-1 inhibition and selectivity profile (COX-1 IC50 = 0.1 μM, SI >1000 over COX-2). Compound 17 was selected as a lead structure for developing the novel COX-1-selective fluorescent probe 22. Fluorescent probe 22 was prepared via click chemistry by installing a nitro-benzoxadiazole motif as a fluorophore into the 3-(furan-2-yl)-N-aryl 5-amino-pyrazole scaffold. Fluorescence probe 22 was tested in ovarian cancer cell line OVCAR-3, confirming its usefulness for targeting and visualizing COX-1 in living cells with confocal microscopy.

Jatinder Kaur

Papers

In Cellulo Generation of Fluorescent Probes for Live-Cell Imaging of Cylooxygenase-2.

Rare earth doped CaWO4 and CaMoO4 thin films for white light emission

Do nitric oxide-releasing drugs offer a potentially new paradigm for the management of cardiovascular risks in diabetes?

Prediction of COVID-19 pervasiveness in six major affected states of India and two-stage variation with temperature.

Development of Fluorescence Imaging Probes for Labeling COX-1 in Live Ovarian Cancer Cells.