Respiratory Tract Infections in Diabetes – Lessons From Tuberculosis and Influenza to Guide Understanding of COVID-19 Severity

Patients with type-2 diabetes (T2D) are more likely to develop severe respiratory tract infections. Such susceptibility has gained increasing attention since the global spread of Coronavirus Disease 2019 (COVID-19) in early 2020. The earliest reports marked T2D as an important risk-factor for severe forms of disease and mortality across all adult age groups. Several mechanisms have been proposed for this increased susceptibility, including pre-existing immune dysfunction, a lack of metabolic flexibility due to insulin resistance, inadequate dietary quality or adverse interactions with antidiabetic treatments or common comorbidities. Some mechanisms that predispose patients with T2D to severe COVID-19 may indeed be shared with other previously characterized respiratory tract infections. Accordingly, in this review, we give an overview of response to Influenza A virus and to Mycobacterium tuberculosis (Mtb) infections. Similar risk factors and mechanisms are discussed between the two conditions and in the case of COVID-19. Lastly, we address emerging approaches to address research needs in infection and metabolic disease, and perspectives with regards to deployment or repositioning of metabolically active therapeutics

Genome-scale constraint-based modeling of Geobacter metallireducens

Background: Geobacter metallireducens was the first organism that can be grown in pure culture to completely oxidize organic compounds with Fe(III) oxide serving as electron acceptor. Geobacter species, including G. sulfurreducens and G. metallireducens, are used for bioremediation and electricity generation from waste organic matter and renewable biomass. The constraint-based modeling approach enables the development of genome-scale in silico models that can predict the behavior of complex biological systems and their responses to the environments. Such a modeling approach was applied to provide physiological and ecological insights on the metabolism of G. metallireducens. Results: The genome-scale metabolic model of G. metallireducens was constructed to include 747 genes and 697 reactions. Compared to the G. sulfurreducens model, the G. metallireducens metabolic model contains 118 unique reactions that reflect many of G. metallireducens\u27 specific metabolic capabilities. Detailed examination of the G. metallireducens model suggests that its central metabolism contains several energy-inefficient reactions that are not present in the G. sulfurreducens model. Experimental biomass yield of G. metallireducens growing on pyruvate was lower than the predicted optimal biomass yield. Microarray data of G. metallireducens growing with benzoate and acetate indicated that genes encoding these energy-inefficient reactions were up-regulated by benzoate. These results suggested that the energy-inefficient reactions were likely turned off during G. metallireducens growth with acetate for optimal biomass yield, but were up-regulated during growth with complex electron donors such as benzoate for rapid energy generation. Furthermore, several computational modeling approaches were applied to accelerate G. metallireducens research. For example, growth of G. metallireducens with different electron donors and electron acceptors were studied using the genome-scale metabolic model, which provided a fast and cost-effective way to understand the metabolism of G. metallireducens. Conclusion: We have developed a genome-scale metabolic model for G. metallireducens that features both metabolic similarities and differences to the published model for its close relative, G. sulfurreducens. Together these metabolic models provide an important resource for improving strategies on bioremediation and bioenergy generation

Tissue Engineering in Oral and Maxillofacial Surgery : From Lab to Clinics

Regenerative medicine aims at the functional restoration of tissue malfunction, damage or loss, and can be divided into three main approaches. Firstly, the cell-based therapies, where cells are administered to re-establish a tissue either directly or through paracrine functions. Secondly, the often referred to as classical tissue engineering, consisting of the combined use of cells and a bio-degradable scaffold to form tissue. Thirdly, there are material-based approaches, which have made significant advances which rely on biodegradable materials, often functionalized with cellular functions (De Jong et al. 2014). In 1993, Langer and Vacanti, determined tissue engineering as an “interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function”. They published this definition in Science in 1993. Tissue engineering has been classically thought to consist of three elements: supporting scaffold, cells and regulating factors such as growth factors (Fig. 1). Depending on the tissue to be regenerated, all three vary. Currently, it is known, that many other factors may have an effect on the outcome of the regenerate. These include factors enabling angiogenesis, physical stimulation, culture media, gene delivery and methods to deliver patient specific implants (PSI) (Fig. 2). During the past two decades, major obstacles have been tackled and tissue engineering is currently being used clinically in some applications while in others it is just taking its first baby steps.Peer reviewe

Photodegradation of organic pollutants RhB dye using UV simulated sunlight on ceria based TiO2 nanomaterials for antibacterial applications

To photo-catalytically degrade RhB dye using solar irradiation, CeO2 doped TiO2 nanocomposites were synthesized hydrothermally at 700 °C for 9 hrs. All emission spectra showed a prominent band centered at 442 nm that was attributed to oxygen related defects in the CeO2-TiO2 nanocrystals. Two sharp absorption bands at 1418 cm−1 and 3323 cm−1 were attributed to the deformation and stretching vibration, and bending vibration of the OH group of water physisorbed to TiO2, respectively. The photocatalytic activities of Ce-TiO2 nanocrystals were investigated through the degradation of RhB under UV and UV+ visible light over a period of 8 hrs. After 8 hrs, the most intense absorption peak at 579 nm disappeared under the highest photocatalytic activity and 99.89% of RhB degraded under solar irradiation. Visible light-activated TiO2 could be prepared from metal-ion incorporation, reduction of TiO2, non-metal doping or sensitizing of TiO2 using dyes. Studying the antibacterial activity of Ce-TiO2 nanocrystals against E. coli revealed significant activity when 10 μg was used, suggesting that it can be used as an antibacterial agent. Its effectiveness is likely related to its strong oxidation activity and superhydrophilicity. This study also discusses the mechanism of heterogeneous photocatalysis in the presence of TiO2

Ionic interactions to tune mechanical and electrical properties of hydrated liquid crystal graphene oxide films

Considerable improvements have been obtained in physical and mechanical properties of free standing liquid crystal graphene oxide (LCGO) films in their hydrated state, by modification of LCGO dispersions with a low quantity of chloride salts. Addition of salts to LCGO dispersions result in an increase of the storage and loss moduli and viscosity through the interaction between cations and functional groups of LCGO, with the magnitude of increase being dependent upon the concentration of the salt added. A viscosity increase of between 30× and 300× (depending on the salt type) is recorded when salt is added at a concentration as low as 80 mM while storage and loss moduli increase up to 23× and 29×, respectively. Free standing films made from the salt treated LCGO dispersions contained up to 26% water in their structure and were observed to have significantly improved mechanical (2× to 5× increase) and electrical properties (decreased surface resistance up to approximately 670×) compared to free standing films prepared without chloride salts. The influence of the salts on properties of LCGO dispersions and their hydrated free standing films is postulated as a complex interplay of many factors such as the size of cations, the valency of positive charge of the cations, ratio of charge and cations size, as well as the hygroscopic nature of the salts

Sulfate-induced stomata closure requires the canonical ABA signal transduction machinery

Phytohormone abscisic acid (ABA) is the canonical trigger for stomatal closure upon abiotic stresses like drought. Soil-drying is known to facilitate root-to-shoot transport of sulfate. Remarkably, sulfate and sulfide—a downstream product of sulfate assimilation—have been independently shown to promote stomatal closure. For induction of stomatal closure, sulfate must be incorporated into cysteine, which triggers ABA biosynthesis by transcriptional activation of NCED3. Here, we apply reverse genetics to unravel if the canonical ABA signal transduction machinery is required for sulfate-induced stomata closure, and if cysteine biosynthesis is also mandatory for the induction of stomatal closure by the gasotransmitter sulfide. We provide genetic evidence for the importance of reactive oxygen species (ROS) production by the plasma membrane-localized NADPH oxidases, RBOHD, and RBOHF, during the sulfate-induced stomatal closure. In agreement with the established role of ROS as the second messenger of ABA-signaling, the SnRK2-type kinase OST1 and the protein phosphatase ABI1 are essential for sulfate-induced stomata closure. Finally, we show that sulfide fails to close stomata in a cysteine-biosynthesis depleted mutant. Our data support the hypothesis that the two mobile signals, sulfate and sulfide, induce stomatal closure by stimulating cysteine synthesis to trigger ABA production

FeNi@N-doped Graphene Core-Shell Nanoparticles on Carbon Matrix Coupled with MoS2 Nanosheets as a Competent Electrocatalysts for Efficient Hydrogen Evolution Reaction

This is the final version. Available on open access from Wiley via the DOI in this recordSynthesis of noble-metal-free electrocatalysts for green hydrogen production is crucial to overcoming the energy demand of modern society. One of the most competitive and alternative noble-metal-free electrocatalysts for HER is Molybdenum disulfide (MoS2) based composites. Herein, MoS2 nanosheets grow on FeNi@N-doped graphene nanoparticles/N-doped carbon matrix (FeNi@NG/NCM@MoS2), using the hydrothermal method. FeNi@NG/NCM@MoS2 hybrid displays outstanding HER performance with a low overpotential of 79 mV at 10 mA cm-2, a small Tafel slope of 40.2 mV dec-1, and high durability. First-principles density functional theory (DFT) simulations confirm the electron transformation from FeNi alloy to NG surface of FeNi@NG particle and subsequently further transfer to MoS2 nanosheets which decrease the Gibbs free energy (ΔGH* ≈ -0.08 eV) and local work function for enhanced HER activities. Our work highlights the understanding of electron transfer in demonstrating the kinetic reaction of the HER process and offers a new avenue for constructing efficient MoS2-based electrocatalysts.National Natural Science Foundation of ChinaJiangsu University of Science and Technology, Chin

Growth of MoS2 nanosheets on M@N-doped carbon particles (M= Co, Fe or CoFe Alloy) as an efficient electrocatalyst toward hydrogen evolution reaction

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe design and synthesis of a highly active noble metal-free electrocatalyst for hydrogen evolution reaction (HER) from water splitting are crucial for renewable energy technologies. Herein, we report the growth of molybdenum disulfide (MoS2) on N-doped carbon encapsulated metal particles (M@NDC@MoS2, where M= Co, Fe or CoFe alloy) as a highly active electrocatalyst for HER. The hierarchical MoS2 nanosheets are grown on M@NDC using the hydrothermal method. Our results show that CoFe@NDC@MoS2 hybrid spheres exhibit excellent HER performance with an overpotential of 64 mV at a current density of 10 mA cm-2 and a small Tafel slope of 45 mV dec-1. In addition, CoFe@NDC@MoS2 hybrid spheres have good long-term stability and durability in acidic conditions. Besides, density functional theory (DFT) simulations of the proposed catalysts are performed and suggest that the superior catalytic activity of CoFe@NDC@MoS2 is due to the optimal electron transfer from CoFe@NDC nanoparticles to MoS2 nanosheets. This electron transfer facilitates H+ interaction and adsorption, leading to a decreased Gibbs free energy (ΔGH* ≈ 0.08 eV) and local work function on the surface, which consequently enhances the HER performance