Novel huperzine A based NMDA antagonists: insights from molecular docking,ADME/T and molecular dynamics simulation studies

Huperzine A (HupA) is an alkaloidal natural product and drug isolated from Chinese herb Huperzia serrata, which is a potent selective anticholinesterase inhibitor. HupA has symptomatic, cognitive-enhancing and protective effect on neurons against amyloid beta-induced oxidative injury and antagonizing N-methyl-d-aspartate receptors by blocking the ion channels. The present study aimed to identify the docking, ADME/T and molecular dynamics simulation parameters of a library of 40 analogues which can correlate the binding affinity, conformational stability and selectivity of the ligands towards NMDA receptor through in silico approach. Glide molecular docking analysis was performed for the designed analogues to understand the binding mode and interactions. MD simulations were performed to explain the conformational stability and natural dynamics of the interaction in physiological environmental condition of protein–ligand complex affording a better understanding of chemical-scale interactions between HupA and its analogues with NMDA channel that could potentially benefit the development of new drugs for neurodegenerative diseases involving NMDA receptors.

The in silico study explores the structural behavior and binding affinities of 40 novel analogues of huperzine A. Novel NMDA receptor antagonists have been virtually identified by molecular docking, ADME/T and molecular dynamics simulation studies.     

Elastic distortion determining conduction in BiFeO3 phase boundaries

It is now well-established that boundaries separating tetragonal-like (T) and rhombohedral-like (R) phases in BiFeO₃ thin films can show enhanced electrical conductivity. However, the origin of this conductivity remains elusive. Here, we study mixed-phase BiFeO₃ thin films, where local populations of T and R can be readily altered using stress and electric fields. We observe that phase boundary electrical conductivity in regions which have undergone stress-writing is significantly greater than in the virgin microstructure. We use high-end electron microscopy techniques to identify key differences between the R–T boundaries present in stress-written and as-grown microstructures, to gain a better understanding of the mechanism responsible for electrical conduction. We find that point defects (and associated mixed valence states) are present in both electrically conducting and non-conducting regions; crucially, in both cases, the spatial distribution of defects is relatively homogeneous: there is no evidence of phase boundary defect aggregation. Atomic resolution imaging reveals that the only significant difference between non-conducting and conducting boundaries is the elastic distortion evident – detailed analysis of localised crystallography shows that the strain accommodation across the R–T boundaries is much more extensive in stress-written than in as-grown microstructures; this has a substantial effect on the straightening of local bonds within regions seen to electrically conduct. This work therefore offers distinct evidence that the elastic distortion is more important than point defect accumulation in determining the phase boundary conduction properties in mixed-phase BiFeO₃.

The localized crystallography of conducting and non-conducting phase boundaries in mixed-phase BiFeO₃ is directly compared using scanning transmission electron microscopy techniques.

The complexity of electrical conductivity in domain walls in BiFeO₃ (and in ferroics in general) is as multifaceted as ever. Various influences such as point defect accumulation, octahedral rotations, magnetic interactions and electrostatic discontinuities are thought to be possible mechanisms at play,^1–8 either alone or in combination. The research area of domain wall conductivity is currently flourishing and the view that domain walls offer exciting prospects in terms of engineering systems in which the domain walls act as distinct identities to the domains which they separate is now widely accepted. We believe that it is pertinent timing to address a lack of experimental investigations providing meaningful direct comparison of the localised crystallography and defect structure responsible for observed enhanced electrical conductivity. This study is stimulated by the interesting discoveries of conductive phase boundaries, specifically, in mixed-phase BiFeO₃.^9,10 By tuning the local populations of the tetragonal-like (T) and rhombohedral-like (R) phases in BiFeO₃ thin films via electric and stress fields, we demonstrate that electrical conductivity along phase boundaries is significantly greater after stress-writing. We probe the key crystallographic differences between the R–T boundaries created via stress, compared to those already present in the as-grown microstructures, to disentangle the mechanism determining electrical conduction in mixed-phase BiFeO₃.The growth of BiFeO₃ on substrates enforcing a large in-plane compressive strain drives the formation of monoclinic phases that are approximately rhombohedral (R) and tetragonal (T). Similar to materials such as PbZr_0.53Ti_0.47O₃ that straddle a morphotropic phase boundary, highly strained BiFeO₃ can readily undergo phase transitions between the R and T phases (and vice versa). The high-strain T phase exhibits a tetragonal-like symmetry (almost P4mm) with a c/a ratio of ∼1.2; the Fe displacement towards one of the apical oxygens along [001]_pc results in fivefold oxygen coordinated Fe, and an enhanced polarisation roughly 1.5 times that of the bulk single crystal.^7,11 The R phase, on the other hand, resembles the rhombohedral bulk phase (almost R3c), where the Fe is octahedrally coordinated, with a ferroelectric distortion along the pseudocubic [111]_pc axis, and antiferrodistortive rotations of the FeO₆ octahedra around [111]_pc occur. The crystal structure and misfit strain associated with the native (as-grown) R and T phases is reported elsewhere, both theoretically^12–15 and experimentally,^6,7,16–21 making it well-known that the ferroelectric and the antiferrodistortive degrees of freedom in mixed-phase BiFeO₃ set it apart from other typical perovskites. Notably, despite the ample evidence provided on phase reversal and characterisation of the as-grown phases, most of the literature (especially regarding electric field cycling of the mixed-phase state) has been primarily concerned with X-ray diffraction (XRD) i.e. global measurements that will not necessarily pick up on the more subtle, atomic-scale aspects of structure local to the phase boundaries. The importance of the study described herein resides in the uniqueness of creating microstructures such that both the as-grown and stress-induced R–T phase boundaries can be included within one single cross-sectional transmission electron microscopy (TEM) lamella; this gives the best possible scenario to allow meaningful direct comparison of the localised crystallography and defect structure responsible for the observed enhanced electrical conductivity found at stress-induced phase boundaries.     

Early osteoblastic activity on TiO2 thin films decorated with flower-like hierarchical Au structures

Titanium alloys are the most commonly used dental and orthopedic implant materials due to their proven biocompatibility and mechanical properties. The native oxide layer (TiO₂ layer) formed on such Ti-based implants acts as the self-protecting layer against possible ion release. Increasing the oxide layer thickness further on such TiO₂ implants even opens the triggering of the osseointegration process if the oxide layer is having a certain degree of roughness, preferably higher. This work reports a novel photocatalytic patterning of sputter deposited TiO₂ layers with flower-like Au structures to enhance the early osteoblastic activity. The prepared hierarchical Au structures, composed of micro- and nanoscale features on the top, lead to improved number of filopodia formation. This suggest that proposed Au–TiO₂ surface may foster the cell attachment and as well as cell proliferation.

Flower-like hierarchical Au structures, composed of micro- and nanoscale features, lead to higher number of filopodia formation on TiO₂ thin films.     

Quantum dot-sensitized O-linked heptazine polymer photocatalyst for the metal-free visible light hydrogen generation

Metal-free organic polymer photocatalysts have attracted dramatic attention in the field of visible light-induced hydrogen evolution reaction (HER). Herein, we showed a polymeric O-linked heptazine polymer (OLHP) decorated with S, N co-doped graphene quantum dots (S,N-GQDs) as a photosensitizer to generate hydrogen upon quantum dot sensitization. Both of these heptazine-based systems show effective photosensitization with strong π–π interactions and enhanced photocatalytic H₂ generation (24 times) as metal-free systems. Electrochemical impedance and optical measurements show effective charge transfer kinetics with decreased charge recombination, which is responsible for the enhanced photocatalytic activity. As a result, a significant high apparent quantum yield (AQY) with highest value of 10.2% was obtained for our photocatalyst OLHP/S,N-GQD10.

A polymeric O-linked heptazine polymer (OLHP) decorated with S, N co-doped graphene quantum dots (S,N-GQDs) as a photosensitizer to utilize visible light (λ > 420 nm) for hydrogen generation.     

Demystifying the mist: Sources of microbial bioload in dental aerosols

The risk of transmitting airborne pathogens is an important consideration in dentistry and has acquired special significance in the context of recent respiratory disease epidemics. The purpose of this review, therefore, is to examine (1) what is currently known regarding the physics of aerosol creation, (2) the types of environmental contaminants generated by dental procedures, (3) the nature, quantity, and sources of microbiota in these contaminants and (4) the risk of disease transmission from patients to dental healthcare workers. Most dental procedures that use ultrasonics, handpieces, air-water syringes, and lasers generate sprays, a fraction of which are aerosolized. The vast heterogeneity in the types of airborne samples collected (spatter, settled aerosol, or harvested air), the presence and type of at-source aerosol reduction methods (high-volume evacuators, low volume suction, or none), the methods of microbial sampling (petri dishes with solid media, filter paper discs, air harvesters, and liquid transport media) and assessment of microbial bioload (growth conditions, time of growth, specificity of microbial characterization) are barriers to drawing robust conclusions. For example, although several studies have reported the presence of microorganisms in aerosols generated by ultrasonic scalers and high-speed turbines, the specific types of organisms or their source is not as well studied. This paucity of data does not allow for definitive conclusions to be drawn regarding saliva as a major source of airborne microorganisms during aerosol generating dental procedures. Well-controlled, large-scale, multi center studies using atraumatic air harvesters, open-ended methods for microbial characterization and integrated data modeling are urgently needed to characterize the microbial constituents of aerosols created during dental procedures and to estimate time and extent of spread of these infectious agents.     

Age-related changes in oral motor-control strategies during unpredictable load demands in humans

To investigate age-related changes in oral motor strategies in response to unpredictable load demands. Sixty-five healthy children (aged 3–17 yr) were divided into five age-groups based on their dental eruption stages and compared with a group of healthy adults (aged 18–35 yr). Each participant was asked to perform a standardized motor control task involving ‘pulling’ and ‘holding’ a force transducer with the anterior teeth. Different loads were attached to the force transducer in an unpredictable manner. The temporal force profile was divided into two time-segments (an initial segment and a later segment). The peak force and peak force rate during the initial time-segment, and the holding force and intra-trial variability (coefficient of variation) during the later time-segment, were measured. The results showed no differences in the peak force, peak force rate, holding force, and force variability in children compared with adults. However, the trends in the data evaluated using a segmented regression analysis showed that a breakpoint (abrupt change) consistently occurred in the late-mixed dentition group (age 9–11 yr) for most of the outcome variables. The results indicate that while the motor control strategies in children appear to be similar to those in adults, there is a shift in the oral motor developmental trend during the late-mixed dentition stage.