Exploring the Structural Attributes of Yoda1 for the Development of New-Generation Piezo1 Agonist Yaddle1 as a Vaccine Adjuvant Targeting Optimal T Cell Activation.

Piezo1, a mechano-activated ion channel, has wide-ranging physiological and therapeutic implications, with the ongoing development of specific agonists unveiling cellular responses to mechanical stimuli. In our study, we systematically analyzed the chemical subunits in Piezo1 protein agonist Yoda1 to comprehend the structure-activity relationship and push forward next-generation agonist development. Preliminary screening assays for Piezo1 agonism were performed using the Piezo1-mCherry-transfected HEK293A cell line, keeping Yoda1 as a positive control. We introduce a novel Piezo1 agonist Yaddle1 (34, 0.40 µM), featuring a trifluoromethyl group, with further exploration through in vitro studies and density functional theory calculations, emphasizing its tetrel interactions, to act as an ambidextrous wedge between the domains of Piezo1. In contrast to the poor solubility of the established agonist Yoda1, our results showed that the kinetic solubility of Yaddle1 (26.72 ± 1.8 µM at pH 7.4) is 10-fold better than that of Yoda1 (1.22 ± 0.11 µM at pH 7.4). Yaddle1 (34) induces Ca2+ influx in human CD4+ T cell, suggesting its potential as a vaccine adjuvant for enhanced T cell activation.

Simultaneous conversion of chromium and malachite green coexists in halophilic bacterium Halomonas xianhensis SUR308 isolated from a solar saltern.

Many industries are known to use heavy metals like chromium (Cr) to fix dyes in the fabrication processes and malachite green (MG) as colorant. Alkalinity, elevated temperature, or salinity of the industrial effluents makes conventional physicochemical removal of MG and hexavalent chromium [Cr(VI)] more difficult to apply and demands to perceive potential cost-effective and environment-friendly treatment methods to eliminate or convert them into less toxic compounds. Here, we report simultaneous removal and bioconversion of MG and Cr(VI) by a halophilic biofilm-forming bacterium Halomonas xianhensis SUR308. It can efficiently produce exopolysaccharides as extracellular polymeric substances (EPS) and form biofilm under oxygen limiting condition. The reduction of hexavalent chromium [Cr(VI)] to trivalent chromium [Cr(III)] is about 100%, and 95% after 84 h of growth in shaken and stagnant culture, respectively. The strain completely decolorizes MG after 48 h of growth in shaken culture. Furthermore, we found that strain SUR308 can efficiently detoxify chromium by reduction and degrades MG via producing various intermediate products simultaneously. Most interestingly, such conversions can also take place in alkaline environment and in environment where substantial amount of salt is present. These unique features of strain SUR308 make it suitable for the simultaneous remediation of toxic heavy metals and hazardous dye even from the environment having higher pH and salinity. The detail molecular mechanism of the bioconversion with its application in open environment would be the future research focus for bioprospecting strain SUR308.

Retraction: Differential detection and quantification of cyclic AMP and other adenosine phosphates in live cells.

Retraction of 'Differential detection and quantification of cyclic AMP and other adenosine phosphates in live cells' by Sujoy Das et al., Chem. Commun., 2017, 53, 7600-7603.

Development of a new fluorescent probe for cysteine detection in processed food samples.

Cysteine is a crucial amino acid, found in a huge amount in protein-rich foods. We focused our research to determine the amount of free cysteine consumed highly in foods such as pork, beef, poultry, eggs, dairy, red peppers, soybeans, broccoli, brussels sprouts, oats, and wheat germs. A newly designed carbazole-pyridine-based fluorescent probe (CPI) has been introduced for quantitative estimation of cysteine (Cys) with a "turn on" fluorescence in some popular processed food samples chosen from our daily diet. CPI shows both naked eye and UV-visible color changes upon interaction with cysteine. The binding approach between CPI and Cys at biological pH has been thoroughly explored by UV-visible and fluorescence spectroscopy. From Job's plot analysis, 1:1 stoichiometric reaction between CPI and Cys is observed with a detection limit of 3.8 µM. NMR, ESI mass spectrometry, and time-dependent density functional theory (TD-DFT) study enlightens the formation of more stable product CPI-Cys. The "turn on" response of the probe CPI occurs due to the interruption of intra-molecular charge transfer (ICT) process upon reacting with cysteine. Moreover, CPI is a very stable, cost-effective compound and exhibits excellent real-time selectivity towards Cys over all other comparative biorelevant analytes. Interestingly, our proposed method is much advantageous as it is able to estimate cysteine predominantly by screening out other comparative biocomponents found in different protein-rich foods.

Visualisation of DCP, a nerve agent mimic, in Catfish brain by a simple chemosensor.

A chemosensor, 3-aminophenol-based rhodamine conjugate (ARC) has been developed for visualisation of diethylchlorophosphate (DCP), mimic of a chemical warfare agent, in Catfish brain. The simple detection of DCP by "turn-on" fluorescence property of the chemosensor makes it unique for easy and rapid in vivo and in vitro detection of DCP with the detection limit of 5.6 nM.

2'-Deoxy-5-(hydroxymethyl)cytidine: estimation in human cancer cells with a simple chemosensor.

A pyrrole-based rhodamine conjugate (CS-1) has been developed and characterized for the selective detection and quantification of 2'-deoxy-5-(hydroxymethyl)cytidine (5hmC) in human cancer cells with a simple chemosensing method.

First Chemosensor for Selective Detection and Quantification of L-4-Hydroxyproline in Collagen and Other Bio Samples.

Amino pyridine-based rhodamine conjugate (APR) has been developed as a first chemosensor for selective detection and quantification of L-4-Hydroxyproline (Hyp). The "turn-on" fluorescence property of the chemosensor makes it unique for easy estimation of Hyp in collagen and biological samples.

Differential detection and quantification of cyclic AMP and other adenosine phosphates in live cells.

A new naphthol-based rhodamine derivative (NpRD) has been developed for the selective and differential detection of adenosine 3',5'-cyclic monophosphate (cAMP) and adenosine phosphates (APs) (ATP, ADP, and AMP) from other nucleotides. The simple detection and quantification of cAMP in human blood cells and in other samples based on the 'turn on' fluorescence properties of this chemosensor through colorimetry or fluorometry makes it unique for probable application in high throughput screening.

Selective fluorescence sensing and quantification of uric acid by naphthyridine-based receptor in biological sample.

Naphthyridine-based fluorescent probe H1 was synthesized and characterized for the quantification and selective detection of Uric Acid (UA) in live cell. In presence of UA, H1 forms the specific host-guest complex mainly through intermolecular hydrogen bonding and aromatic stacking which produces "turn-off" fluorescence. The probe and UA is found to be 1:1 stoichiometry on the basis of absorption and fluorescence titrations. The probe H1 has been shown to detect UA up to 0.6µM at pH 7.4. DFT-TDDFT calculations were performed in order to demonstrate the sensing mechanism and the electronic properties of the receptor-donor complex. The selectivity was evaluated in Vero cells in the presence of UA with other purine derivatives, structurally similar to UA. It was found to exhibit no cytotoxicity effect in tested concentration of H1 and good membrane permeability for the detection of UA in living cell system. The unknown concentration of UA in serum and urine can be measured easily using the fluorescence property of probe H1.