HSA over BSA: Selective detection of Human Serum Albumin via a naphtho [2,1-b] furan-based system.

Human serum albumin (HSA) is an important biomarker that can be used for the early diagnosis of many diseases. In this work, a TICT probe bearing fused naphtho-furan scaffold (NPNF) was developed and employed in the selective turn-on sensing of HSA. The probe's selectivity towards HSA was observed using steady-state fluorescence experiments, with limit of quantitation in micromolar levels. NPNF's capability to exclusively detect HSA over BSA was further studied/rationalized using anisotropy and time-resolved studies. Molecular docking was used to shed light on the location of NPNF in the subdomain IB of HSA. The practical application of the probe was also demonstrated by the detection of HSA in urine and the HSA-assisted detection of cerium.

Development and Validation of a Fluorogenic Probe for Lysosomal Zinc Release.

Zinc homeostasis, which allows optimal zinc utilization in diverse life processes, is responsible for the general well-being of human beings. This paper describes developing and validating an easily accessible indole-containing zinc-specific probe in the cellular milieu. The probe was synthesized from readily available starting materials and was subjected to steady-state fluorescence studies. It showed selective sensing behavior towards Zn2+ with reversible binding. The suppression of PET (Photoinduced Electron Transfer) and ESIPT (Excited State Intramolecular Proton Transfer) elicited selectivity, and the detection limit was 0.63 µM (LOQ 6.8 µM). The zinc sensing capability of the probe was also screened in the presence of low molecular weight ligands [LMWLs] and showed interference only with GSH and ATP. It is non-toxic and can detect zinc in different cell lines under various stress conditions such as inflammation, hyperglycemia, and apoptosis. The probe could stain the early and late stages of apoptosis in PAN-2 cells by monitoring the zinc release. Most experiments were conducted without external zinc supplementation, showing its innate ability to detect zinc.

To Quench or Not: Extending a ß-Carboline Fluorophore for TNT Detection in Aqueous Media via Simultaneous ESPT Destabilization and AIE.

Molecules relying on the excited-state intramolecular proton transfer/excited-state proton transfer (ESIPT/ESPT) mechanism are widely used in material science. In the current work, a known ß-carboline-based probe TrySy was used to selectively detect explosive trinitrotoluene (TNT) in water. Compared to conventional TNT sensing, which relies mainly on the quenching of the fluorescence signal, TrySy could perform nanomolar detection of TNT via ESPT destabilization and AIE, with a significant fluorescence output. The mechanism followed was validated by computational and experimental results.

Genome analysis of SARS-CoV-2 isolates from a population reveals the rapid selective sweep of a haplotype carrying many pre-existing and new mutations.

To understand the mechanism underlying the evolution of SARS-CoV-2 in a population, we sequenced 92 viral genomes from Assam, India. Analysis of these and database sequences revealed a complete selective sweep of a haplotype in Assam carrying 13 pre-existing variants, including a high leap in frequency of a variant on ORF8, which is involved in immune evasion. A comparative study between sequences of same lineage and similar time frames in and outside Assam showed that 10 of the 13 pre-existing variants had a frequency ranging from 96 to 99%, and the remaining 3 had a low frequency outside Assam. Using a phylogenetic approach to infer sequential occurrences of variants we found that the variant Phe120del on ORF8, which had a low frequency (1.75%) outside Assam, is at the base of the phylogenetic tree of variants and became totally fixed (100%) in Assam population. Based on this observation, we inferred that the variant on ORF8 had a selective advantage, so it carried the haplotype to reach the100% frequency. The haplotype also carried 32 pre-existing variants at a frequency from 1.00 to 80.00% outside Assam. Those of these variants that are more closely linked to the S-protein locus, which often carries advantageous mutations and is tightly linked to the ORF8 locus, retained higher frequencies, while the less tightly linked variants showed lower frequencies, likely due to recombination among co- circulating variants in Assam. The ratios of non-synonymous substitutions to synonymous substitutions suggested that some genes such as those coding for the S-protein and non-structural proteins underwent positive selection while others were subject to purifying selection during their evolution in Assam. Furthermore, we observed negative correlation of the Ct value of qRT-PCR of the patients with abundant ORF6 transcripts, suggesting that ORF6 can be used as a marker for estimating viral titer. In conclusion, our in-depth analysis of SARS-CoV-2 genomes in a regional population reveals the mechanism and dynamics of viral evolution.

Comparative pangenomic analysis of predominant human vaginal lactobacilli strains towards population-specific adaptation: understanding the role in sustaining a balanced and healthy vaginal microenvironment.

The vaginal microenvironment of healthy women has a predominance of Lactobacillus crispatus, L. iners, L. gasseri, and L. jensenii. The genomic repertoire of the strains of each of the species associated with the key attributes thereby regulating a healthy vaginal environment needs a substantial understanding.We studied all available human strains of the four lactobacilli across different countries, isolated from vaginal and urinal sources through phylogenetic and pangenomic approaches. The findings showed that L. iners has the highest retention of core genes, and L. crispatus has more gene gain in the evolutionary stratum. Interestingly, L. gasseri and L. jensenii demonstrated major population-specific gene-cluster gain/loss associated with bacteriocin synthesis, iron chelating, adherence, zinc and ATP binding proteins, and hydrolase activity. Gene ontology enrichment analysis revealed that L. crispatus strains showed greater enrichment of functions related to plasma membrane integrity, biosurfactant, hydrogen peroxide synthesis, and iron sequestration as an ancestral derived core function, while bacteriocin and organic acid biosynthesis are strain-specific accessory enriched functions. L. jensenii showed greater enrichment of functions related to adherence, aggregation, and exopolysaccharide synthesis. Notably, the key functionalities are heterogeneously enriched in some specific strains of L. iners and L. gasseri.This study shed light on the genomic features and their variability that provides advantageous attributes to predominant vaginal Lactobacillus species maintaining vaginal homeostasis. These findings evoke the need to consider region-specific candidate strains of Lactobacillus to formulate prophylactic measures against vaginal dysbiosis for women's health.

Multi-Omics Analysis Demonstrates the Critical Role of Non-Ethanolic Components of Alcoholic Beverages in the Host Microbiome and Metabolome: A Human- and Animal-Based Study.

It is known that alcoholic beverages alter the human gut microbiome. This study focused on the potential impact of non-ethanolic ingredients in whisky on the gut bacteriome. A pilot study was carried out on 15 whisky drinkers, 5 rice beer drinkers, and 9 non-drinkers to determine the effect of alcoholic beverages on the host microbiome and metabolome. Additionally, a mouse model was used to assess the differential impact of three whisky brands (each with an equal ethanol concentration). The results indicate that the non-ethanolic components have an impact on the gut microbiome, as well as on the metabolites in blood and feces. The amount of Prevotella copri, a typical core Indian gut bacterium, decreased in both the human and mouse groups of whisky type 1, but an increase in abundance of Helicobacteriaceae (p = 0.01) was noticed in both groups. Additionally, the alcohol-treated cohorts had lower levels of short-chain fatty acids (SCFAs), specifically butyric acid, and higher amounts of lipids and stress marker IL1-ß than the untreated groups (p = 0.04-0.01). Furthermore, two compounds, ethanal/acetaldehyde (found in all the whisky samples) and arabitol (unique to whisky type 1), were tested in the mice. Similar to the human subjects, the whisky type 1 treated mouse cohort and the arabitol-treated group showed decreased levels of Prevotella copri (p = 0.01) in their gut. The results showed that non-ethanolic compounds have a significant impact on host gut bacterial diversity and metabolite composition, which has a further vital impact on host health. Our work further emphasizes the need to study the impact of non-ethanolic ingredients of alcoholic beverages on host health.

Visible light sensing of ions by a cyanoquinoxaline 1,4-dioxide-based probe and its applications.

Inducting newer fluorophores for colourimetry/fluorimetry-assisted analyte sensing is of great importance. Towards this end, we have shown the application of quinoxaline-1,4-dioxide bioactive molecules for the first time as potential probes for cations and anions. The molecule (ACQ) used in this study is soluble in water and provides specific colour output upon interaction with copper and palladium ions. Changing the solvent to DMSO allows a change in selectivity to fluoride ions via pink to blue colour change. All the ions detected showed quenching of the fluorescence signal upon interaction with the probe. Analysis of the Stern-Volmer plot indicated the predominant role of static quenching in the selective ion-sensing behaviour of the probe. The stoichiometry of the ACQ and ion was 2 : 1 in the case of Cu2+ and Pd2+, whereas a ratio of 1 : 1 was seen in the case of F-. We have also applied ACQ to probe the above-mentioned analytes in practical settings.

Copper acetate catalysed C-C bond formation en route to the synthesis of spiro indanedione cyclopropylpyrazolones.

This article reports the synthesis of spiro compounds based on an indanedione-cyclopropane-pyrazolone framework. The reaction relied upon the Michael-initiated ring closure strategy and was carried out under Cu(OAc)2 catalysis, assisted by an oxygen atmosphere and the base Et3N. The final compounds were obtained as an inseparable mixture in most cases with modest to good yields using diverse substrates. Among the two plausible routes, computational studies indicated the feasibility of a route which involves a four-membered Cu containing intermediate. Given the generic nature of the developed method, it may be utilised to synthesise other analogous spiro systems.

Strain-tunable triple point Fermions in diamagnetic rare-earth half-Heusler alloys.

Topologically non-trivial electronic structure is a feature of many rare-earth half-Heusler alloys, which host atoms with high spin-orbit coupling bringing in the non-triviality. In this article, using the first-principles simulations, rare-earth half-Heusler YPdBi, ScPdBi, LaPdBi, LuPdBi, YPtBi and LuPtBi alloys are studied under strain to reveal multiple band inversions associated with topological phase transitions. From our simulations we find that, as a result of first band-inversion, the Brillouin zone of the diamagnetic half-Heusler alloys hosts eight triple points whereas, the second band inversion causes the emergence of sixteen more triple points. These band-inversions are observed to be independent of the spin-orbit coupling and are the reason behind increasing occupation of bismuth 7s orbitals as volume of the unit cell increases. The surface electronic transport in different triple point semi-metallic phases is found to evolve under strain, as the number of Fermi arcs change due to multiple band inversions. Once the second band inversion occurs, further application of tensile strain does not increase the number of triple points and Fermi arcs. However, increasing tensile strain (or decreasing compressive strain) pushes the triple point crossing to higher momenta, making them more effective as source of highly mobile electrons. These observations make a pathway to tune the bulk as well as surface transport through these semi-metals by application of tensile or compressive strain depending on the unstrained relative band-inversion strength of the material.

Identification of the conserved long non-coding RNAs in myogenesis.

BACKGROUND: Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. RESULTS: In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. CONCLUSIONS: With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

Strain driven emergence of topological non-triviality in YPdBi thin films.

Half-Heusler compounds exhibit a remarkable variety of emergent properties such as heavy-fermion behaviour, unconventional superconductivity and magnetism. Several of these compounds have been predicted to host topologically non-trivial electronic structures. Remarkably, recent theoretical studies have indicated the possibility to induce non-trivial topological surface states in an otherwise trivial half-Heusler system by strain engineering. Here, using magneto-transport measurements and first principles DFT-based simulations, we demonstrate topological surface states on strained [110] oriented thin films of YPdBi grown on (100) MgO. These topological surface states arise in an otherwise trivial semi-metal purely driven by strain. Furthermore, we observe the onset of superconductivity in these strained films highlighting the possibility of engineering a topological superconducting state. Our results demonstrate the critical role played by strain in engineering novel topological states in thin film systems for developing next-generation spintronic devices.

Iodine assisted synthesis of CF3 appended spirodihydrofuryl/cyclopropyl oxindoles by changing the active methylene sources.

This paper describes the synthesis of two distinct types of CF3-containing spirooxindoles by varying the active methylene sources. The reaction was carried out in DMSO, assisted by molecular iodine and Na2CO3via systematic application of Michael reaction and iodine mediated cyclisation. With 5-methyl-2,4-dihydro-3H-pyrazol-3-one as the methylene source, the final products obtained were spirodihydrofuropyrazolyl oxindoles, whereas 1H-indene-1,3(2H)-dione as the methylene source gave the final compounds spirocyclopropyl oxindoles. Modest to good yields were obtained for both the spiro systems.

Composition and in silico structural analysis of fibroin from liquid silk of non-mulberry silkworm Antheraea assamensis.

Silk is spun from the liquid precursor known as liquid silk secreted from the posterior part and stored in the silk gland lumen with occurrence of many momentary events. The liquid silk in the silk gland is transformed to the spun silk fibre. In this study the elucidation of the protein components of liquid silk from the posterior part of the silk gland (PSG) of saturniid silkworm Antheraea assamensis along with its structural characterization has been reported. The 3D model of the N-terminal amorphous portion with some repeat crystalline motifs (19-255) of core protein fibroin has also been constructed. 1D and 2D electrophoresis revealed the homo-dimeric structure of the silk protein. Secondary structure analysis by Circular dichroism, FTIR spectroscopy showed α helical structural component as predominant conformation in the liquid silk. The crystalline structure investigated through X ray diffraction (XRD) analysis also revealed the presence of less ordered amorphous α helical conformation in the liquid silk. The 3D structural model proposed of the residues from 19 to 255 has revealed structural stability throughout the molecular dynamics simulation process. This study will provide the detailed structural information and in silico analysis of the core protein present in the liquid silk of PSG.

Thickness-dependent magneto-transport properties of topologically nontrivial DyPdBi thin films.

DyPdBi (DPB) is a topological semimetal which belongs to the rare-earth-based half-Heusler alloy family. In this work, we studied the thickness-dependent structural and magneto-transport properties of DPB thin films (20 to 60 nm) grown using pulsed laser deposition. The DPB thin films show (110) oriented growth on MgO(100) single crystal substrates. Longitudinal resistance data indicate metallic surface states dominated carrier transport and the suppression of semiconducting bulk state carriers for films ≤40 nm. We observe the weak antilocalization (WAL) effect and Shubnikov-de Hass (SdH) oscillations in the magneto-transport data. The presence of a single coherent transport channel (α∼ -0.50) is observed in the Hikami-Larkin-Nagaoka (HLN) fitting of WAL data. The power law temperature dependence of phase coherence length (LØ ) ∼ T-0.50 indicates the observation of the 2D WAL effect and the presence of topological nontrivial surface states for films ≤40 nm. The 60 nm sample shows semiconducting resistivity behavior at higher temperature (>180 K) and HLN fitting results (α∼ -0.72, LØ âˆ¼ T-0.68 ) indicate the presence of partial decoupled top and bottom surface states. The Berry phase ∼π is extracted for thin films ≤40 nm, which further demonstrates the presence of Dirac fermions and nontrivial surface states. Band structure parameters are extracted by fitting SdH data to the standard Lifshitz-Kosevich formula. The sheet carrier concentration and cyclotron effective mass of carriers decrease with increasing thickness (20 nm to 60 nm) from ∼1.35 × 1012 cm-2 to 0.68 × 1012 cm-2 and from ∼0.26 me to 0.12 me, respectively. Our observations suggest that samples with a thickness ≤40 nm have transport properties dominated by surface states and samples with a thickness ≥60 nm have contributions from both bulk and surface states.

Metal-Enhanced Fluorescence Study in Aqueous Medium by Coupling Gold Nanoparticles and Fluorophores Using a Bilayer Vesicle Platform.

Gold nanoparticles (AuNPs) display excellent plasmonic properties, which are expected to assist fluorescence enhancement for dyes, and the phenomenon is known as "metal-enhanced fluorescence" (MEF). In this study, we demonstrate AuNP-induced MEF for a modified bipyridine-based construct 4-(pyridine-2-yl)-3H-pyrrolo[2,3-c]quinoline (PPQ) when it binds with biologically important Zn2+. Importantly, this phenomenon is observed under aqueous conditions in a biocompatible bilayer vesicle platform. When PPQ binds with Zn2+ to form the complex in the presence of appropriate AuNPs, MEF is evident once compared with the fluorescence intensity in the absence of AuNPs. Among the three different sizes of AuNPs used, the enhancement is observed with an average diameter of 33 nm, whereas 18 and 160 nm do not show any enhancement. A possible mechanism is ascribed to the radiating plasmons of the AuNPs, which can couple with the emission frequencies of the fluorophore under a critical distance-dependent arrangement. We witness that the enhancement in fluorescence is accompanied with a reduction in lifetime components. It is proposed that the mechanism may be predominantly derived from the enhancement of an intrinsic radiative decay rate and partly from the localized electric field effect. Overall, this work shows a rational approach to design fluorophore-metal configurations with the desired emissive properties and a basis for a useful nanophotonic technology under biological conditions.

Functionalized Chitosan-Carbon Dots: A Fluorescent Probe for Detecting Trace Amount of Water in Organic Solvents.

A novel nanoprobe was designed and synthesized by functionalizing chitosan-carbon dots (CDs) with a modified bipyridine-based heterocyclic molecule, 4-(pyridine-2-yl)-3H-pyrrolo[2,3-c]quinoline (PPQ), to detect trace amount of water via fluorescence methods. The functionalized CDs (PPQ-CDs) were thoroughly characterized using dynamic light scattering, UV-vis, X-ray diffraction, Fourier transform infrared, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, and NMR techniques. The modified fluorescence intensity of PPQ-CDs was found to be an excellent indicator for water in organic solvents. The PPQ-CDs showed very weak fluorescence intensity in organic solvents due to a possible photoinduced electron transfer (PET) process between PPQ pyrrole nitrogen and acceptor groups of CDs. However, sequential addition of trace amount of water led to continuous enhancement in the fluorescence intensity for the PPQ-CD nanocomposites. The mechanism was proposed to follow suppression of the PET process due to the formation of "free-ions" by the proton transfer from the CD carboxyl group to pyrrole nitrogen through water bridging. The limit of water detection was determined to be 0.023% (v/v) in DMSO.

Selective Sensing of Iron by Pyrrolo[2,3-c]Quinolines.

This paper reports development of an iron sensor, 2-(3H-pyrrolo[2,3-c]quinolin-4-yl)aniline (APQ). The fluorophore facilitates micromolar detection of Fe3+/Fe2+ in the presence of various cations, including well-known interfering cations Co2+and Cu2+ by the process of fluorescence quenching. Graphical Abstract.

Total synthesis of the plant alkaloid racemic microthecaline A: first example of a natural product bearing a tricyclic quinoline-serrulatane scaffold.

The first total synthesis of racemic microthecaline A, a quinoline serrulatane alkaloid, isolated from the Australian desert plant Eremophila microtheca is described. The natural product was synthesized in ten steps, starting from ethyl 4-bromo-6-methoxy-8-methylquinoline-3-carboxylate in 8% overall yield.