Sea squirt-inspired bio-derived tissue sealants.

Sea squirts' or tunicates' bodies are composed of cellulose nanofibers and gallol- functionalized proteins. These sea creatures are known to heal their injuries under seawater by forming crosslinks between gallols and functional groups from other proteins in their bodies. Inspired by their wound healing mechanism, herein, we have developed a tissue sealant using zein (a plant-based protein) and tannic acid (gallol-containing polyphenol). Except for fibrin- based sealants, most commercial surgical adhesives, and sealants available today are derived from petroleum products that compromise their biodegradability. They often have complicated and multi-step synthesis processes that ultimately affect their affordability. To overcome this challenge, we ensured that these sea squirt-inspired tissue sealants are bio-based, easily synthesized, and low-cost. The sealants were studied on their own and with a food-grade enzyme transglutaminase. The adhesion performances of the sealants were found to be higher than physiological pressures in seven out of nine different tissue substrates studied here. Their performance was also better than or on par with the FDA-approved fibrin sealant Tisseel. Ex vivo models demonstrate instant sealing of leaking wounds in less than a minute. The sealants were not only cytocompatible but also showed complete wound healing on par with sutures and Tisseel when applied in vivo on skin incisions in rats. Overall, these sea squirt-inspired bio-based sealants show great potential to replace currently available wound closure methods.

Adaptive exhaustion during prolonged intermittent hypoxia causes dysregulated skeletal muscle protein homeostasis.

Nocturnal hypoxaemia, which is common in chronic obstructive pulmonary disease (COPD) patients, is associated with skeletal muscle loss or sarcopenia, which contributes to adverse clinical outcomes. In COPD, we have defined this as prolonged intermittent hypoxia (PIH) because the duration of hypoxia in skeletal muscle occurs through the duration of sleep followed by normoxia during the day, in contrast to recurrent brief hypoxic episodes during obstructive sleep apnoea (OSA). Adaptive cellular responses to PIH are not known. Responses to PIH induced by three cycles of 8 h hypoxia followed by 16 h normoxia were compared to those during chronic hypoxia (CH) or normoxia for 72 h in murine C2C12 and human inducible pluripotent stem cell-derived differentiated myotubes. RNA sequencing followed by downstream analyses were complemented by experimental validation of responses that included both unique and shared perturbations in ribosomal and mitochondrial function during PIH and CH. A sarcopenic phenotype characterized by decreased myotube diameter and protein synthesis, and increased phosphorylation of eIF2α (Ser51) by eIF2α kinase, and of GCN-2 (general controlled non-derepressed-2), occurred during both PIH and CH. Mitochondrial oxidative dysfunction, disrupted supercomplex assembly, lower activity of Complexes I, III, IV and V, and reduced intermediary metabolite concentrations occurred during PIH and CH. Decreased mitochondrial fission occurred during CH. Physiological relevance was established in skeletal muscle of mice with COPD that had increased phosphorylation of eIF2α, lower protein synthesis and mitochondrial oxidative dysfunction. Molecular and metabolic responses with PIH suggest an adaptive exhaustion with failure to restore homeostasis during normoxia. KEY POINTS: Sarcopenia or skeletal muscle loss is one of the most frequent complications that contributes to mortality and morbidity in patients with chronic obstructive pulmonary disease (COPD). Unlike chronic hypoxia, prolonged intermittent hypoxia is a frequent, underappreciated and clinically relevant model of hypoxia in patients with COPD. We developed a novel, in vitro myotube model of prolonged intermittent hypoxia with molecular and metabolic perturbations, mitochondrial oxidative dysfunction, and consequent sarcopenic phenotype. In vivo studies in skeletal muscle from a mouse model of COPD shared responses with our myotube model, establishing the pathophysiological relevance of our studies. These data lay the foundation for translational studies in human COPD to target prolonged, nocturnal hypoxaemia to prevent sarcopenia in these patients.

Mutants of Helicobacter pylori IMPDH: Kinetics and in silico Studies to Determine the Structural and Functional Role of Key Amino Acids.

The emergence of antibiotic-resistant strains of Helicobacter pylori necessitates the development of novel therapeutic strategies to fight against its infection. Recently, the enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) has emerged as a promising target to treat bacterial infections due to its crucial role in the de novo purine biosynthesis pathway. The differences between the prokaryotic and eukaryotic IMPDHs, in the NAD+ binding domain and flap region, allow the identification of pathogen-specific inhibitors. In the present study, seven point mutants of wild type Helicobacter pylori IMPDH are constructed by site-directed mutagenesis, and characterized using in silico and kinetic studies. Point mutations in the NAD+ binding domain and the flap region are shown to impart significant changes in the enzyme's structure and function. In addition, the product inhibition characteristics of the Arg396-Tyr397 dyad (RY dyad) show that both the residues are important for water activation in the reaction. The results obtained are beneficial for the design and development of small-molecule inhibitors, capable of species-specific inhibition.

Graphene templated growth of copper sulphide 'flowers' can suppress electromagnetic interference.

With increasing usage of electronic gadgets in various fields, the problem of electromagnetic interference (EMI) has become eminent. To suppress this interference, lightweight materials that are non-corrosive in nature and easy to fabricate, design, integrate and process are in great demand. In the present study, we have grown copper sulphide 'flowers' on graphene oxide by a facile one pot hydrothermal technique. The growth time of the "flower-like" structure was optimised based on structural (XRD) and morphological analysis (SEM). Then, the as-prepared structures were dispersed in a PVDF matrix using melt blending. The bulk AC electrical conductivity and EMI shielding ability of the prepared composite were assessed, and it was observed that the nanocomposites exhibited an EMI shielding effectiveness up to -25 dB manifesting in 86% absorption of the incoming EM waves at a thickness of only 1 mm. Moreover, it was also observed that addition of hybrid nanoparticles has a better effect on the electromagnetic (EM) shielding performance compared to when the nanoparticles are added separately in terms of both total shielding effectiveness as well as absorption performance. A minimum skin depth of 0.38 mm was observed in the case of the hybrid nanostructure.

Synthesis and In Vitro Enzymatic Studies of New 3-Aryldiazenyl Indoles as Promising Helicobacter pylori IMPDH Inhibitors.

BACKGROUND & OBJECTIVE: Helicobacter pylori infection is one of the primary causes of peptic ulcer followed by gastric cancer in the world population. Due to increased occurrences of multi-drug resistance to the currently available antibiotics, there is an urgent need for a new class of drugs against H. pylori. Inosine 5'-monophosphate dehydrogenase (IMPDH), a metabolic enzyme plays a significant role in cell proliferation and cell growth. It catalyses guanine nucleotide synthesis. IMPDH enzyme has been exploited as a target for antiviral, anticancer and immunosuppressive drugs. Recently, bacterial IMPDH has been studied as a potential target for treating bacterial infections. Differences in the structural and kinetic parameters of the eukaryotic and prokaryotic IMPDH make it possible to target bacterial enzyme selectively. METHODS: In the current work, we have synthesised and studied the effect of substituted 3-aryldiazenyl indoles on Helicobacter pylori IMPDH (HpIMPDH) activity. The synthesised molecules were examined for their inhibitory potential against recombinant HpIMPDH. RESULTS: In this study, compounds 1 and 2 were found to be the most potent inhibitors amongst the database with IC50 of 0.8 ± 0.02µM and 1 ± 0.03 µM, respectively. CONCLUSION: When compared to the most potent known HpIMPDH inhibitor molecule C91, 1 was only four-fold less potent and can be a good lead for further development of selective and potent inhibitors of HpIMPDH.

Ultrafast Self-Healable Interfaces in Polyurethane Nanocomposites Designed Using Diels-Alder "Click" as an Efficient Microwave Absorber.

In the recent times, multifunctional materials have attracted immense interest. Self-healing polymers are in great demand in almost every coating application. With an increase in electromagnetic (EM) pollution, curbing the same has become an urgent necessity. Lightweight coatings and conducting polymeric materials are being highly researched upon in this regard, and combining these properties with self-healing systems would open new avenues in EM interference (EMI) shielding (specifically in the microwave frequency domain) applications. In the current study, a novel approach toward the development of microwave shielding materials capable of self-healing through microwave heating has been attempted. A covalently cross-linked material was developed using Diels-Alder (DA) chemistry, which shows self-healing properties when stimulated by heating. Herein, reduced graphene oxide grafted with magnetite nanoparticles (rGO/Fe3O4) was covalently cross-linked to thermoplastic polyurethane using DA chemistry. The addition of multiwalled carbon nanotubes into these nanocomposites led to exceptional EM wave shielding and self-healing properties through a synergistic effect. The synergism led to exceptional EMI shielding of -36 dB, primarily through absorption in the microwave region of the EM spectrum. When used in the form of thin coatings of about 1 mm in thickness, the shielding value reached -28 dB, manifesting in more than 99% attenuation of EM waves through absorption. The material was also found to be capable of healing scratches or cuts through microwave irradiation.

Phase specific dispersion of functional nanoparticles in soft nanocomposites resulting in enhanced electromagnetic screening ability dominated by absorption.

The effect of phase specific localisation of MWNTs (multiwalled carbon nanotubes) and magnetic FeNi (iron-nickel) alloy particles on bulk electrical conductivity and electromagnetic (EM) wave attenuation was investigated in biphasic co-continuous blends of PVDF/SMA (polyvinylidene fluoride/styrene maleic anhydride). It is envisaged that packing different functional nanoparticles in a given phase of a co-continuous blend can impede the charge transport phenomenon and the overall dispersion state. Therefore, phase specific localisation can facilitate the tuning of the functional properties in biphasic blends. This strategy was adopted here wherein conducting MWNTs and magnetic FeNi particles were surface tailored to position them in different phases during processing. As the functional particles prefer the PVDF phase by virtue of thermodynamics, by harnessing amine functional moieties on the surface, their localisation can be tuned to position them in the SMA phase (due to amine-anhydride coupling). This was achieved by sequential mixing during processing. For the best combination, SET was observed to be -23 dB when MWNTs were localised in the SMA phase and magnetic particles in the PVDF phase of the blend with an impressive 92% absorption of the incident EM radiation.