Leveraging an enzyme/artificial substrate system to enhance cellular persulfides and mitigate neuroinflammation

Persulfides and polysulfides, collectively known as the sulfane sulfur pool along with hydrogen sulfide (H₂S), play a central role in cellular physiology and disease. Exogenously enhancing these species in cells is an emerging therapeutic paradigm for mitigating oxidative stress and inflammation that are associated with several diseases. In this study, we present a unique approach of using the cell''s own enzyme machinery coupled with an array of artificial substrates to enhance the cellular sulfane sulfur pool. We report the synthesis and validation of artificial/unnatural substrates specific for 3-mercaptopyruvate sulfurtransferase (3-MST), an important enzyme that contributes to sulfur trafficking in cells. We demonstrate that these artificial substrates generate persulfides in vitro as well as mediate sulfur transfer to low molecular weight thiols and to cysteine-containing proteins. A nearly 100-fold difference in the rates of H₂S production for the various substrates is observed supporting the tunability of persulfide generation by the 3-MST enzyme/artificial substrate system. Next, we show that the substrate 1a permeates cells and is selectively turned over by 3-MST to generate 3-MST-persulfide, which protects against reactive oxygen species-induced lethality. Lastly, in a mouse model, 1a is found to significantly mitigate neuroinflammation in the brain tissue. Together, the approach that we have developed allows for the on-demand generation of persulfides in vitro and in vivo using a range of shelf-stable, artificial substrates of 3-MST, while opening up possibilities of harnessing these molecules for therapeutic applications.

A persulfide/hydrogen sulfide generation strategy through artificial substrates for 3-mercaptopyruvate sulfurtransferase (3-MST) is reported, which enhances cellular persulfides, attenuates reactive oxygen species (ROS), and alleviates inflammation.     

Mathematical modeling of localized melting around graphite nodules during laser surface hardening of austempered ductile iron

An attempt has been made to mathematically predict the optimum conditions of laser surface hardening (LSH) of austempered ductile iron (ADI) that can ensure a predominantly martensitic microstructure and preclude partial/complete dissolution of graphite nodules in the laser hardened zone during laser irradiation. The exercise involves prediction of the thermal profile (using the Ashby and Easterling model), and consequently, the carbon diffusion profile around the graphite nodules at different depths from the surface for the given conditions of LSH. Microstructural investigations have been carried out by optical and scanning electron microscopy to study the morphology, shape and width of the partially/completely melted graphite nodules as a function of the LSH parameters. Finally, the predicted maximum width of the melted zone around the graphite nodules is compared with the relevant experimental data to validate the proposed model.     

Charge and/or spin limits for black holes at a non-commutative scale

We study the cosmological dynamics for R ^p exp(λ R) gravity theory in the metric formalism, using dynamical systems approach. Considering higher-dimensional FRW geometries in case of an imperfect fluid which has two different scale factors in the normal and extra dimensions, we find the exact solutions, and study its behaviour and stability for both vacuum and matter cases. It is found that stable solutions corresponding to accelerated expansion at late times exist, which can describe the inflationary era of the Universe. We also study the evolution of scale factors both in the normal and extra dimensions for different values of anisotropy parameter and the number of extra dimensions for such a scenario.     

Heterodimers based on CoPt3-Au nanocrystals with tunable domain size

We describe an approach to synthesize colloidal nanocrystal heterodimers composed of CoPt(3) and Au. The growth is based on the nucleation of gold domains on preformed CoPt(3) nanocrystals. It is a highly versatile methodology which allows us to tune independently the size of the two domains in each dimer by varying several reaction parameters. The statistical analysis of the distribution of the domain sizes in the dimers and the compositional mapping achieved by dark field imaging and energy dispersive spectroscopy confirm that the two domains in each dimer are indeed made of CoPt(3) and Au, respectively. Structural characterization by high-resolution transmission electron microscopy shows that the two domains, both having cubic fcc Bravais lattice, can share a common {111}, {100}, or {110} facet, depending on the size of the initial CoPt(3) seeds. The magnetization measurements evidence a ferromagnetic CoPt(3) phase with a relatively low anisotropy as a consequence of their disordered crystalline structure, regardless of the presence of a Au tip. We believe that this prototype of nanocrystal dimer, which can be manipulated under air, can find several applications in nanoscience, as the Au section can be exploited as the preferential anchor point for various molecules, while the CoPt(3) domain can be used for magnetic detection.     

Transparent,Versatile Chemical Vapor Sensor Using Supramolecular Assembly of Block Copolymer and Carbon Nanotubes

Here, a simple and novel approach is reported for developing a new class of transparent chemical vapor sensors with a low power consumption, high sensitivity, good selectivity, and excellent environmental stability by depositing multiwalled carbon nanotubes on prepatterned polymer substrates using supramolecular assembly. The patterned polymer substrates were fabricated from block copolymers, whereas the supramolecular assembly between the carbon nanotubes and block copolymer is utilized for the selective localization of carbon nanotubes at the block copolymer–air interface. The thin film devices made from the block copolymer and carbon nanotubes are highly transparent (transmittance > 90%) and respond to a wide range of solvents of different polarity, both hydrophilic and hydrophobic, with good selectivity and fast response time.

     

Strong lensing of a regular black hole with an electrodynamics source

In this paper we have investigated the gravitational lensing phenomenon in the strong field regime for a regular, charged, static black holes with non-linear electrodynamics source. We have obtained the angle of deflection and compared it to a Schwarzschild black hole and Reissner Nordström black hole with similar properties. We have also done a graphical study of the relativistic image positions and magnifications. We hope that this method may be useful in the detection of non-luminous bodies like this current black hole.     

A black hole with quantum core

A model black hole, holding a ‘quantum core’ characterized by the Planck order matter density, is revisited here. Based on the quantum improved Newton’s potential drawn out of the loop quantum cosmology we propose a Schwarzschild class, quantum improved black hole line-element that upholds the existence of Planck-dense quantum matter core. Causality is kept preserved in this proposal. Quite in a natural way the quantum core emerges closely homogeneous in its interior matter distribution. The radius of the quantum core turns out to be necessarily proportional to one-third power of the black hole mass. Hawking process of black hole evaporation leads to a shrinking quantum core, and as the mass of black hole approaches near about the Planck mass, the rate of evaporation diminishes rapidly and eventually leaves a cold remnant having a Planck order mass. Proposed model supports the standard quantum geometrical logarithmic correction to black hole entropy-area law.