Supramolecular alternating copolymers with highly efficient fluorescence resonance energy transfer.

This article reports alternating supramolecular copolymerization of two naphthalene-diimide (NDI)-derived building blocks (NDI-1 and NDI-2) under thermodynamic control. Both monomers contain a central NDI chromophore, attached to a hydrocarbon-chain and a carboxylic-acid group. The NDI core in NDI-2 is symmetrically substituted with two butane-thiol groups, which makes it distinct from NDI-1. In decane, a 1 : 1 mixture of NDI-1 and NDI-2 shows spontaneous gelation and a typical fibrillar network, unlike the behavior of either of the components individually. The solvent-dependent UV/vis spectrum of the mixed sample in decane shows bathochromically shifted sharp absorption bands and a sharp emission band (holds a mirror-image relationship) with a significantly small Stokes shift compared to those in CHCl3, indicating J-aggregation. In contrast, the aggregated spectra of the individual monomers show broad structureless features, suggesting ill-defined aggregates. Cooling curves derived from the temperature-dependent UV/vis spectroscopy studies revealed early nucleation and a signature of well-defined cooperative polymerization for the mixed sample, unlike either of the individual components. Molecular dynamics simulations predicted the greatest dimer formation tendency for the NDI-1 + NDI-2 (1 : 1), followed by pure NDI-1 and NDI-2. Theoretical studies further revealed a partial positive charge in the NDI ring of NDI-1 when compared to NDI-2, promoting the alternating stacking propensity, which is also favored by the steric factor as NDI-2 is core-substituted with alkyl thiols. Such theoretical predictions fully corroborate with the experimental results showing 1 : 1 stoichiometry (from Job's plot) of the two monomers, indicating alternate stacking sequences in the H-bonded (syn-syn catemer type) supramolecular copolymer. Such alternating supramolecular copolymers showed highly efficient (>93%) fluorescence resonance energy transfer (FRET).

Evaluation of Knowledge, Attitude, and Practice Regarding Hand Hygiene Practices among Inpatients of Kalinga Institute of Medical Sciences Bhubaneswar: A Preliminary Study.

Background: Health-care-associated infection or nosocomial infection is defined as patients getting an infection on admission to the hospital if they were not infected or incubating the infection before admission. Hand hygiene is the most important measure that can avoid the transmission of germs and can prevent health-care-associated infections. Materials and Methods: A hospital-based cross-sectional study was conducted between June 2020 to July 2021 with the objective to evaluate knowledge, attitude, and practice of hand hygiene among the inpatients of Kalinga Institute of Medical Sciences, Bhubaneswar. A predesigned structured questionnaire was used for data collection. Knowledge and attitude of the participants were assessed using prevalidated 9 point and 6 point scale. Practice of the health-care providers (HCPs) toward health hygiene observed by the patients was also assessed using 6 point scale. Results: Majority of the participants had average knowledge score (56.7%) and average attitude score (62.0%) on hand hygiene, whereas their observation on the practice of hand hygiene among HCPs has given bad score (50.7%). Males have significantly good knowledge (P = 0.0001) and attitude score (P = 0.00097) compared to female. Similarly higher educational level participants had significantly good knowledge (P = 0.0002) and attitude score (P = 0.0053) on hand hygiene. Conclusions: The findings of this study indicate that there is insufficient hand hygiene awareness among the inpatients in a tertiary care hospital population mainly among the female and less educated participants. Hence, development of community-based hand hygiene promotion programs for the general public are the need of the hour.

Removal of Non-Specifically Bound Proteins Using Rayleigh Waves Generated on ST-Quartz Substrates.

Label-free biosensors are plagued by the issue of non-specific protein binding which negatively affects sensing parameters such as sensitivity, selectivity, and limit-of-detection. In the current work, we explore the possibility of using the Rayleigh waves in ST-Quartz devices to efficiently remove non-specifically bound proteins via acoustic streaming. A coupled-field finite element (FE) fluid structure interaction (FSI) model of a surface acoustic wave (SAW) device based on ST-Quartz substrate in contact with a liquid loading was first used to predict trends in forces related to SAW-induced acoustic streaming. Based on model predictions, it is found that the computed SAW body force is sufficient to overcome adhesive forces between particles and a surface while lift and drag forces prevent reattachment for a range of SAW frequencies. We further performed experiments to validate the model predictions and observe that the excitation of Rayleigh SAWs removed non-specifically bound (NSB) antigens and antibodies from sensing and non-sensing regions, while rinsing and blocking agents were ineffective. An amplified RF signal applied to the device input disrupted the specific interactions between antigens and their capture antibody as well. ST-quartz allows propagation of Rayleigh and leaky SH-SAW waves in orthogonal directions. Thus, the results reported here could allow integration of three important biosensor functions on a single chip, i.e., removal of non-specific binding, mixing, and sensing in the liquid phase.

Prevention of Covid-19 affected patient using multi robot cooperation and Q-learning approach: a solution.

Combat with the novel corona virus (COVID-19) has become challenging for all the frontline warriors like, medic people, police and other service provider. Many technology and intelligent algorithms have been developed to set the boundary in its incremental growth. This paper proposed a concept to set the boundary on spreading of this disease among the medic people, who are directly exposed to the COVID-19 patient. To reduce their risk to be infected, we have designed the theoretical model of the medic robot to provide medical services to the confirmed case patient. This paper explains the deployment and execution of assigned work of medic robot for patient carrying, delivering food, medications and handling the emergency health services. The medic robots are divided into various group based on their works. The COVID-19 area is considered as a multi-robot environment, where multiple medic robots will work simultaneously. To achieve the multi-robot cooperation and collision avoidance we have implemented the simplest reinforcement learning approach i.e. the Q-learning approach. We have compared the result with respect to the improved-Q-learning approach. A comparative analysis based on parameters like simplicity, objective, deployed robot category and cooperation has been done with some other approaches mentioned in the literature. For simplicity as well as the time and space complexity purpose the results reveal that Q-learning approach is a better consideration. The proposed approach reduces the mortality rate by 2%.

Dienolate Annulation Approach for Assembly of Densely Substituted Aromatic Architectures.

The efficient assembly of complex aromatic structures from simple acyclic building blocks is reported. An anion-cascade union of an enoate and a conjugated imine affords cyclohexenone products, which are readily aromatized to phenols. By engaging the intermediate cyclohexenones with Grignard reagents, a facile addition/elimination proceeds yielding chiral cyclohexadienes, which are then aromatized. In a complementary approach, the cyclohexenone products are converted into enol triflates, which provides a gateway to diverse aromatic architectures following cross-couplings and aromatization steps.

Dramatic Effect of γ-Heteroatom Dienolate Substituents on Counterion Assisted Asymmetric Anionic Amino-Cope Reaction Cascades.

We report a dramatic effect on product outcomes of the lithium ion enabled amino-Cope-like anionic asymmetric cascade when different γ-dienolate heteroatom substituents are employed. For dienolates with azide, thiomethyl, and trifluoromethylthiol substituents, a Mannich/amino-Cope/cyclization cascade ensues to form chiral cyclohexenone products with two new stereocenters in an anti-relationship. For fluoride-substituted nucleophiles, a Mannich/amino-Cope cascade proceeds to afford chiral acyclic products with two new stereocenters in a syn-relationship. Bromide- and chloride-substituted nucleophiles appear to proceed via the same pathway as the fluoride albeit with the added twist of a 3-exo-trig cyclization to yield chiral cyclopropane products with three stereocenters. When this same class of nucleophiles is substituted with a γ-nitro group, the Mannich-initiated cascade is now diverted to a ß-lactam product instead of the amino-Cope pathway. These anionic asymmetric cascades are solvent- and counterion-dependent, with a lithium counterion being essential in combination with etheral solvents such as MTBE and CPME. By altering the geometry of the imine double bond from E to Z, the configurations at the R1 and X stereocenters are flipped. Mechanistic, computational, substituent, and counterion studies suggest that these cascades proceed via a common Mannich-product intermediate, which then proceeds via either a chair (X = N3, SMe, or SCF3) or boat-like (X = F, Cl, or Br) transition state to afford amino-Cope-like products or ß-lactam in the case of X = NO2.

Fluorescence Detection of miRNA-21 Using Au/Pt Bimetallic Tubular Micromotors Driven by Chemical and Surface Acoustic Wave Forces.

In this study, surface acoustic wave (SAW) systems are described for the removal of molecules that are unbound to micromotors, thereby lowering the detection limit of the cancer-related biomarker miRNA-21. For this purpose, in the first step, mass production of the Au/Pt bimetallic tubular micromotor was performed with a simple membrane template electrodeposition. The motions of catalytic Au/Pt micromotors in peroxide fuel media were analyzed under the SAW field effect. The changes in the micromotor speed were investigated depending on the type and concentration of surfactants in the presence and absence of SAW streaming. Our detection strategy was based on immobilization of probe dye-labeled single-stranded probe DNA (6-carboxyfluorescein dye-labeled-single-stranded DNA) to Au/Pt micromotors that recognize target miRNA-21. Before/after hybridization of miRNA-21 (for both w/o SAW and SAW streaming conditions), the changes in the speed of micromotors and their fluorescence intensities were studied. The response of fluorescence intensities was observed to be linearly varied with the increase of the miRNA-21 concentration from 0.5 to 5 nM under both w/o SAW and with SAW. The resulting fluorescence sensor showed a limit of detection of 0.19 nM, more than 2 folds lower compared to w/o SAW conditions. Thus, the sensor and behaviors of Au/Pt tubular micromotors were improved by acoustic removal systems.

Effects of Stereochemistry and Hydrogen Bonding on Glycopolymer-Amyloid-ß Interactions.

Saccharide stereochemistry plays an important role in carbohydrate functions such as biological recognition processes and protein binding. Synthetic glycopolymers with pendant saccharides of controlled stereochemistry provide an attractive approach for the design of polysaccharide-inspired biomaterials. Acrylamide-based polymers containing either ß,d-glucose or ß,d-galactose pendant groups, designed to mimic GM1 ganglioside saccharides, and their small-molecule analogues were used to evaluate the effect of stereochemistry on glycopolymer solution aggregation processes alone and in the presence of Aß42 peptide using dynamic light scattering, gel permeation chromatography-multiangle laser light scattering, and fluorescence assays. Fourier transform infrared and nuclear magnetic resonance (NMR) were employed to determine hydrogen bonding patterns of the systems. The galactose-containing polymer displayed significant intramolecular hydrogen bonding and self-aggregation and minimal association with Aß42, while the glucose-containing glycopolymers showed intermolecular interactions with the surrounding environment and association with Aß42. Saturation transfer difference NMR spectroscopy demonstrated different binding affinities for the two glycopolymers to Aß42 peptide.

Repurposing of Glycine-Rich Proteins in Abiotic and Biotic Stresses in the Lone-Star Tick (Amblyomma americanum).

Tick feeding requires the secretion of a huge number of pharmacologically dynamic proteins and other molecules which are vital for the formation of the cement cone, the establishment of the blood pool and to counter against the host immune response. Glycine-rich proteins (GRP) are found in many organisms and can function in a variety of cellular processes and structures. The functional characterization of the GRPs in the tick salivary glands has not been elucidated. GRPs have been found to play a role in the formation of the cement cone; however, new evidence suggests repurposing of GRPs in the tick physiology. In this study, an RNA interference approach was utilized to silence two glycine-rich protein genes expressed in early phase of tick feeding to determine their functional role in tick hematophagy, cement cone structure, and microbial homeostasis within the tick host. Additionally, the transcriptional regulation of GRPs was determined after exposure to biotic and abiotic stresses including cold and hot temperature, injury, and oxidative stress. This caused a significant up-regulation of AamerSigP-34358, Aam-40766, AamerSigP-39259, and Aam-36909. Our results suggest ticks repurpose these proteins and further functional characterization of GRPs may help to design novel molecular strategies to disrupt the homeostasis and the pathogen transmission.

A Survey of the Structures of US FDA Approved Combination Drugs.

Combination drugs are an important class of US FDA approved pharmaceuticals. These drugs have been on a continuous growth trajectory since the first combination drugs were approved in the 1940s. In this Perspective, we report the first comprehensive compilation and analysis of US FDA approved combination drugs, from the first approval in 1943 through 2018. Our database contains 419 combination drugs, which are represented by 328 unique small molecule structures. Breakdown of these drugs according to disease category, structure, combination composition, and year of approval is presented as well as the top 24 most commonly used small molecule combination drug components. For frequently used small molecule components, we present "relationship diagrams" to aid in the visualization of the many drug combinations these structures are part of. The main body contains 10 disease-focused sections wherein every small molecule component utilized as part of a combination for each disease category is displayed.

Wound Healing and Bone Regeneration in Postextraction Sockets with and without Platelet-rich Fibrin.

CONTEXT AND AIM: In today's world of advanced dentistry, there are various aspects of restorative, esthetic, and surgical processes. Healing of an extraction socket comprises of bone as well as soft-tissue remodeling with maximum dimensional changes occurring during the first 3 months. Platelet-rich fibrin (PRF) was first developed in France as a therapeutic alternative to platelet-rich plasma to overcome many of its limitations. The present study was planned to evaluate and compare wound healing and bone regeneration in extraction sockets with and without PRF. MATERIALS AND METHODS: The present study was carried out on 30 patients selected from the outpatient department over a period of 2½ years starting from May 2013 undergoing extraction of maxillary or mandibular teeth simultaneously to conduct a split-mouth study. The research protocol was approved by the Institutional Ethics Committee governing the use of human subjects in clinical experimentation. STATISTICAL ANALYSIS USED: Descriptive and analytical statistics were calculated using Statistical Package for Social Sciences version 19. Chi-square test was used to assess wound healing score in the two groups while paired t-test was used to compare the bone density in the socket and periapical regions at different time intervals, and unpaired t-test was used for the intergroup comparisons. P < 0.05 was considered to be significant while P < 0.001 was considered highly significant. RESULTS: Patients in PRF group had better healing index when compared to without PRF group. Use of PRF showed a comparable increase in bone density too. CONCLUSION: An appreciable wound healing and bone regeneration was seen in the experimental group when compared to the control sites where no PRF was used substantiating the use of PRF as an inexpensive autologous material for socket preservation and future rehabilitation. The present study, also, showed that minimal operator expertise was required to conduct the procedure of PRF preparation and grafting when compared to bone harvesting from distant sites. The shorter duration between extractions and further rehabilitation obviates the need for a second procedure.

Asymmetric Vinylogous Aza-Darzens Approach to Vinyl Aziridines.

A new asymmetric approach to assemble cis-vinyl aziridines is reported. A reaction of strategically substituted dienolates, decorated with a γ-leaving group, with chiral sulfinimines afforded chiral vinyl aziridine products in good to excellent yields. This is the first systematic study toward the realization of a useful asymmetric vinylogous aza-Darzens reaction. The reaction is initiated by a syn-selective addition, affording cis-vinyl aziridine products after displacement of bromide. The low syn-diastereoselectivity is attributed to competing retro-Mannich pathways.

DNA translocation through polyelectrolyte-modified nanopores: An analytical approximation.

An analytical model for the electrophoretic speed of DNA translocating through nanopore functionalized with polyelectrolyte (PE) brush is developed for the first time. The electrophoretic speed depends on DNA surface potential, applied electric field, viscosity, and permittivity of solution along with velocity and electrostatic potential at liquid-polyelectrolyte layer (PEL) interface where the interface seemed to behave similar to that of a solid-state nanopore wall. Under the limit of Debye-Hückel linearization, the electrostatic potential at liquid-PEL interface and at DNA surface have been calculated. Velocity at liquid-PEL interface has been estimated by assuming a linear variation of hydrodynamic frictional force within the PEL. It is observed that velocity and electrostatic potential at liquid-PEL interface strongly depend on PE charge density and softness parameter. Present analytical results show excellent agreement with exact numerical results (i.e., without any approximation) at a higher salt concentration where Debye-Hückel linearization is applicable.

Aqueous RAFT Synthesis of Glycopolymers for Determination of Saccharide Structure and Concentration Effects on Amyloid ß Aggregation.

GM1 ganglioside is known to promote amyloid-ß (Aß) peptide aggregation in Alzheimer's disease. The roles of the individual saccharides and their distribution in this process are not understood. Acrylamide-based glycomonomers with either ß-d-glucose or ß-d-galactose pendant groups were synthesized to mimic the stereochemistry of saccharides present in GM1 and characterized via 1H NMR and electrospray ionization mass spectrometry. Glycopolymers of different molecular weights were synthesized by aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization and characterized by NMR and GPC. The polymers were used as models to investigate the effects of molecular weight and saccharide unit type on Aß aggregation via thioflavin-T fluorescence and PAGE. High molecular weight (∼350 DP) glucose-containing glycopolymers had a profound effect on Aß aggregation, promoting formation of soluble oligomers of Aß and limiting fibril production, while the other glycopolymers and negative control had little effect on the Aß propagation process.

New Class of Anion-Accelerated Amino-Cope Rearrangements as Gateway to Diverse Chiral Structures.

We report useful new lithium-assisted asymmetric anion-accelerated amino-Cope rearrangement cascades. A strategic nitrogen atom chiral auxiliary serves three critical roles, by (1) enabling in situ assembly of the chiral 3-amino-1,5-diene precursor, (2) facilitating the rearrangement via a lithium enolate chelate, and (3) imparting its influence on consecutive inter- or intramolecular C-C or C-X bond-forming events via resulting chiral enamide intermediates or imine products. The mechanism of the amino-Cope rearrangement was explored with density functional theory. A stepwise dissociation-recombination mechanism was found to be favored. The stereochemistry of the chiral auxiliary determines the stereochemistry of the Cope product by influencing the orientation of the lithium dienolate and sulfinylimine fragments in the recombination step. These robust asymmetric anion-accelerated amino-Cope enabled cascades open the door for rapid and predictable assembly of complex chiral acyclic and cyclic nitrogen-containing motifs in one pot.

Strain-specific Fibril Propagation by an Aß Dodecamer.

Low molecular weight oligomers of amyloid-ß (Aß) have emerged as the primary toxic agents in the etiology of Alzheimer disease (AD). Polymorphism observed within the aggregation end products of fibrils are known to arise due to microstructural differences among the oligomers. Diversity in aggregate morphology correlates with the differences in AD, cementing the idea that conformational strains of oligomers could be significant in phenotypic outcomes. Therefore, it is imperative to determine the ability of strains to faithfully propagate their structure. Here we report fibril propagation of an Aß42 dodecamer called large fatty acid-derived oligomers (LFAOs). The LFAO oligomeric strain selectively induces acute cerebral amyloid angiopathy (CAA) in neonatally-injected transgenic CRND8 mice. Propagation in-vitro occurs as a three-step process involving the association of LFAO units. LFAO-seeded fibrils possess distinct morphology made of repeating LFAO units that could be regenerated upon sonication. Overall, these data bring forth an important mechanistic perspective into strain-specific propagation of oligomers that has remained elusive thus far.

Structural characterization of tick cement cones collected from in vivo and artificial membrane blood-fed Lone Star ticks (Amblyomma americanum).

The Lone Star tick, Amblyomma americanum, is endemic to the southeastern United States and capable of transmitting pathogenic diseases and causing non-pathogenic conditions. To remain firmly attached to the host, the tick secretes a proteinaceous matrix termed the cement cone which hardens around the tick's mouthparts to assist in the attachment of the tick as well as to protect the mouthparts from the host immune system. Cement cones collected from ticks on a host are commonly contaminated with host skin and hair making analysis of the cone difficult. To reduce the contamination found in the cement cone, we have adapted an artificial membrane feeding system used to feed long mouthpart ticks. Cones collected from in vivo and membrane fed ticks are analyzed to determine changes in the cone morphology. Comparisons of the cement cones using light microscopy shows similar structures and color however using scanning electron microscopy the cones have drastically different structures. The in vivo cones contain fibrils, sheets, and are heavily textured whereas cones from membrane fed ticks are remarkably smooth with no distinct structures. Analysis of the secondary protein structures using FTIR-ATR show both in vivo and membrane fed cement cones contain ß sheets but only in vivo cement cones contain helical protein structures. Additionally, proteomic analysis using LC-MS/MS identifies many proteins including glycine rich proteins, metalloproteases, and protease inhibitors. Proteomic analysis of the cones identified both secreted and non-secreted tick proteins. Artificial membrane feeding is a suitable model for increased collection of cement cones for proteomic analysis however, structurally there are significant differences.

Effect of thermodiffusion on pH-regulated surface charge properties of nanoparticle.

Surface properties of nanoparticle are of high importance in the field of biotechnology, drug delivery and micro/nanofabrication. In this article, we developed a comprehensive theoretical model and subsequently solved that numerically to study the effect of thermodiffusion of ions on surface charge properties of nanoparticle. The theoretical study has been done considering silica nanoparticle for two aqueous solutions NaCl and KCl. The effect of solution pH in conjunction with nanoparticle temperature on surface charge density has been obtained for different salt concentrations (1, 10 and 100 mM) and nanoparticle size (diameter of 2 and 100 nm). It is observed from the results that with increasing temperature of the nanoparticle, the negative surface charge density gets higher due to increasing thermodiffusion effect. It is also found out that the magnitude of surface charge density is higher for KCl solution than NaCl solution under same condition which is attributed mostly due to less thermodiffusion of counterions for KCl than NaCl. Present study also shows that magnitude of surface charge density decreases with increasing nanoparticle size until it reaches a limiting value (called critical size) above which the effect of nanoparticle size on surface charge density is insignificant.

Synthesis of 1,2,3,6-Tetrahydropyridines via Aminophosphate Enabled Anionic Cascade and Acid Catalyzed Cyclization Approaches.

Two new approaches for forming 1,2,3,6-tetrahydropyridines are reported. Both reactions employ a strategic phosphate substituent on the nitrogen atom. In the presence of an additional phosphate substituent (X = P = O(OEt)2) an anionic cascade can by triggered upon treatment with base. Alternatively, when X = H the same 1,2,3,6-tetrahydropyridine product can be accessed via an acid catalyzed cyclization.