Versatile Prepolymer Platform for Controlled Tailoring of Quantum Dot Surface Properties.

Quantum dots (QDs) hold immense promise for bioimaging, yet technical challenges in surface engineering limit their wider scientific use. We introduce poly(pentafluorophenyl acrylate) (PPFPA) as a user-friendly prepolymer platform for creating precisely controlled multidentate polymeric ligands for QD surface engineering, accessible to researchers without extensive synthetic expertise. PPFPA combines the benefits of both bottom-up and prepolymer approaches, offering minimal susceptibility to hydrolysis and side reactions for controlled chemical composition, along with simple synthetic procedures using commercially available reagents. Live cell imaging experiments highlighted a significant reduction in nonspecific binding when employing PPFPA, owing to its minimal hydrolysis, in contrast to ligands synthesized by using a conventional prepolymer prone to uncontrolled hydrolysis. This observation underscores the distinct advantage of our prepolymer system. Leveraging PPFPA, we synthesized biomolecule-conjugated QDs and performed QD-based immunofluorescence to detect a cytosolic protein. To effectively label cytosolic targets in such a dense and complex environment, probes must exhibit minimal nonspecific binding and be compact. As a result, QD-immunofluorescence has focused primarily on cell surface targets. By creating compact QD-F(ab')2, we sensitively detected alpha-tubulin with a ∼50-fold higher signal-to-noise ratio compared to organic dye-based labeling. PPFPA represents a versatile and accessible platform for tailoring QD surfaces, offering a pathway to realize the full potential of colloidal QDs in various scientific applications.

Identification of Linomide Derivatives as Potential Anticancer Therapeutics using Molecular Docking Studies.

12 analogs bearing a structural similarity to Linomide, a bonafide anticancer agent were synthesized wherein cyclization of substituted dianilides rendered 4-hydroxyquinolin-2(1H)-ones that were subjected to a Mannich reaction to yield 4-hydroxy-3-(substituted-1-ylmethyl) quinolin-2(1H)-one analogs. Characterization was performed using IR, 1H nuclear magnetic resonance and 13C NMR spectral analysis. Subsequently, in vitro anticancer studies revealed that Compound 4b showed maximum cytotoxicity with IC50 values of 1.539 µM/ml and 1.732 µM/ml against A549 and K562 cell lines respectively. This, however, is lower in comparison with standard Paclitaxel (IC50 values of 0.3 µM/ml for both cell lines). Surprisingly, docking studies at the active site of EGFRK revealed Compound 4b possessed a MolDock Score of -110.2253 that is highly comparable to the standard 4-anilinoquinazoline (MolDock Score of -112.04). Our computational and biological data thus provides an insight on the cytotoxicity of these derivatives and warrants future research that can possibly lead to the development of potent anticancer therapeutics.

Applications of Phyto-Nanotechnology for the Treatment of Neurodegenerative Disorders.

The strategies involved in the development of therapeutics for neurodegenerative disorders are very complex and challenging due to the existence of the blood-brain barrier (BBB), a closely spaced network of blood vessels and endothelial cells that functions to prevent the entry of unwanted substances in the brain. The emergence and advancement of nanotechnology shows favourable prospects to overcome this phenomenon. Engineered nanoparticles conjugated with drug moieties and imaging agents that have dimensions between 1 and 100 nm could potentially be used to ensure enhanced efficacy, cellular uptake, specific transport, and delivery of specific molecules to the brain, owing to their modified physico-chemical features. The conjugates of nanoparticles and medicinal plants, or their components known as nano phytomedicine, have been gaining significance lately in the development of novel neuro-therapeutics owing to their natural abundance, promising targeted delivery to the brain, and lesser potential to show adverse effects. In the present review, the promising application, and recent trends of combined nanotechnology and phytomedicine for the treatment of neurological disorders (ND) as compared to conventional therapies, have been addressed. Nanotechnology-based efforts performed in bioinformatics for early diagnosis as well as futuristic precision medicine in ND have also been discussed in the context of computational approach.

Exploring Pharmacological Mechanisms of Essential Oils on the Central Nervous System.

Essential oils (EOs) have been traditionally used as ancient remedies to treat many health disorders due to their enormous biological activities. As mainstream allopathic medication currently used for CNS disorders is associated with adverse effects, the search to obtain safer alternatives as compared to the currently marketed therapies is of tremendous significance. Research conducted suggests that concurrent utilization of allopathic medicines and EOs is synergistically beneficial. Due to their inability to show untoward effects, various scientists have tried to elucidate the pharmacological mechanisms by which these oils exert beneficial effects on the CNS. In this regard, our review aims to improve the understanding of EOs' biological activity on the CNS and to highlight the significance of the utilization of EOs in neuronal disorders, thereby improving patient acceptability of EOs as therapeutic agents. Through data compilation from library searches and electronic databases such as PubMed, Google Scholar, etc., recent preclinical and clinical data, routes of administration, and the required or maximal dosage for the observation of beneficial effects are addressed. We have also highlighted the challenges that require attention for further improving patient compliance, research gaps, and the development of EO-based nanomedicine for targeted therapy and pharmacotherapy.

Entre o projeto de modernidade e a efetivação da democracia: marcas deixadas na construção da vida social brasileira / Between projecting modernity and putting democracy into practice: marks left in the construction of the Brazilian social life

O presente artigo retoma algumas interpretações sobre o projeto de modernidade, aproximando-as de alguns elementos da formação social brasileira, considerando sua estreita relação para a afirmação e valorização da democracia no Brasil. Além disso, destacam-se interpretações sobre o processo de redemocratização da sociedade brasileira que ressaltam a importância da prática dos movimentos sociais para a validação desse processo.

The present article resumes some interpretations of the project of modernity. It approaches them to some elements of the Brazilian social formation, considering the narrow relationship for the affirmation and the valuation of democracy in Brazil. Moreover, the article stresses the interpretations of the redemocratization of the Brazilian society that show how important the practice of the social movements was to the validation of such a process.

Prótese parcial fixa: solução estética para rebordos anteriores reabsorvidos

No tratamento de reabilitação em pacientes com rebordos anteriores severamente reabsorvidos, a prótese parcial removível é recomendada, uma vez que esta adequa o suporte labial ou cirurgias...

NMR structure of stem-loop D from human rhinovirus-14.

The 5'-cloverleaf of the picornavirus RNA genome is essential for the assembly of a ribonucleoprotein replication complex. Stem-loop D (SLD) of the cloverleaf is the recognition site for the multifunctional viral protein 3Cpro. This protein is the principal viral protease, and its interaction with SLD also helps to position the viral RNA-dependent RNA polymerase (3Dpol) for replication. Human rhinovirus-14 (HRV-14) is distinct from the majority of picornaviruses in that its SLD forms a cUAUg triloop instead of the more common uYACGg tetraloop. This difference appears to be functionally significant, as 3Cpro from tetraloop-containing viruses cannot bind the HRV-14 SLD. We have determined the solution structure of the HRV-14 SLD using NMR spectroscopy. The structure is predominantly an A-form helix, but with a central pyrimidine-pyrimidine base-paired region and a significantly widened major groove. The stabilizing hydrogen bonding present in the uYACGg tetraloop was not found in the cUAUg triloop. However, the triloop uses different structural elements to present a largely similar surface: sequence and underlying architecture are not conserved, but key aspects of the surface structure are. Important structural differences do exist, though, and may account for the observed cross-isotype binding specificities between 3Cpro and SLD.

Characterization of the Saccharomyces cerevisae Y500-4L killer toxin

The strain Saccharomyces cerevisiae Y500-4L, selected from the must of alcohol producing plants, liberates a toxin which is lethal to the commercial yeast produced by Fleischmann Royal Nabisco and other strains of yeast. This toxin was characterized, and the maximum production was obtained after 24 hours of incubation at 25§C in YEPD medium. The maximum activity was achieved between pH 4.1 and 4.5 and between 22 and 25§C and maximum stability in the pH range 3.8 to 4.5 at -10§C. The killer toxin was inactivated by heating at 40§C for 1 hour at pH 4.1. After concentration by ultrafiltration of culture supernatants and purification by gel filtration chromatography, the molecular weight of the purified toxin was estimated by SDS-PAGE to be about 18-20 kDa.

Killer toxin of Saccharomyces cerevisae Y500-4L active against fleischmann and Itaiquara commercial brands of yeast

The strain Saccharomyces cerevisae Y500-4L, previously selected from the must of alcohol producing plants and showing high fermentative and killer capacities, was characterized according to the interactions between the yeasts and examined for curing and detection of dsRNA plasmids, which code for the killer character. The killer yeast S. cerevisae Y500-4L showed considerable killer activity against the Fleischmann and Itaiquara commercial brands of yeast and also against the standard killer yeast K2 (S. diastaticus NCYC 713), K4 (Candida glabrata NCYC 388) and K11(Torulopsis glabrata ATCC 15126). However S. cerevisae Y500-4L showed sensitivity to the killer toxin produced by the standard killer yeasts K8 (Hansenula anomala NCYC 435), K9(Hansenula mrakii NCYC500), K10(Kluyveromyces drosophilarum NCYC575) and K11(Torulopsis glabrata ATCC 15126). No M-dsRNA plasmid was detected in the S. cerevisae Y500-4L strain and these results suggest that the genetic basis for toxin production is encoded by chromosoma DNA. The strain S.cerevisae Y500-4L was more resistant to the loss of the phenotype killer with cycloheximide and incubation at elevated temperatures (40§C) than the standard killer yeast S. cerevisae K1.