Approaches for Mitigating Microbial Biofilm-Related Drug Resistance: A Focus on Micro- and Nanotechnologies

Biofilms play an essential role in chronic and healthcare-associated infections and are more resistant to antimicrobials compared to their planktonic counterparts due to their (1) physiological state, (2) cell density, (3) quorum sensing abilities, (4) presence of extracellular matrix, (5) upregulation of drug efflux pumps, (6) point mutation and overexpression of resistance genes, and (7) presence of persister cells. The genes involved and their implications in antimicrobial resistance are well defined for bacterial biofilms but are understudied in fungal biofilms. Potential therapeutics for biofilm mitigation that have been reported include (1) antimicrobial photodynamic therapy, (2) antimicrobial lock therapy, (3) antimicrobial peptides, (4) electrical methods, and (5) antimicrobial coatings. These approaches exhibit promising characteristics for addressing the impending crisis of antimicrobial resistance (AMR). Recently, advances in the micro- and nanotechnology field have propelled the development of novel biomaterials and approaches to combat biofilms either independently, in combination or as antimicrobial delivery systems. In this review, we will summarize the general principles of clinically important microbial biofilm formation with a focus on fungal biofilms. We will delve into the details of some novel micro- and nanotechnology approaches that have been developed to combat biofilms and the possibility of utilizing them in a clinical setting.     

Importance of van der Waals interaction for organic molecule-metal junctions: adsorption of thiophene on Cu(110) as a prototype

We report ab initio calculations for the interface energetics of a weakly adsorbed organic molecule on a metal surface, which serves as a model interface relevant for organic electronics. The studied thiophene ring is found to be physisorbed on the Cu(110) surface with an adsorption energy of -0.50 eV. Nonlocal correlations, i.e., van der Waals interactions, are solely responsible for the binding in this weakly interacting system, and the choice of the proper exchange-correlation function is crucially important. The adsorption of thiophene lowers the metal work function due to the formation of surface dipoles while no sizable charge transfer is found.     

Approximation of functions of Lipschitz class and solution of Fokker-Planck equation by two-dimensional Legendre wavelet operational matrix

In this paper, Lipschitz class of two-variables is considered. This is the genralization of well-known Lipschitz class of functions. A new estimator of functions belonging to generalized Lipschitz class has been obtained. Also, the solutions for the Fokker-Planck equations have been obtained for two different cases by two-dimensional Legendre wavelet operational matrix method. The approximated solutions of the time-and space-Fokker Planck equation have been compared with the exact solutions and the solutions obtained by homotopy perturbation method. The proposed scheme is simple, effective and suitable for the solution of Fokker-Planck equation.

     

Reaction of OH radical and ozone with methyl salicylate – a DFT study

A theoretical study on the reaction mechanism of methyl salicylate (MeSA), a green leaf volatile organic compound with OH radical and ozone, has been carried out using density functional theory methods using B3LYP, M06‐2X and MPW1K functionals with 6‐311++G(d,p) basis set. The atmospheric degradation pathways of MeSA with OH radical are studied under two different pathways, viz. H‐atom abstraction and electrophilic addition of OH radical. The hydrogen abstraction from –OH group is found to be the dominant reaction channel with small barrier height. Likewise, the electrophilic addition of OH radicals at the para position of MeSA is found to be favourable rather than the ortho and meta positions because of the small barrier height. However, the reaction of MeSA with respect to the addition of O₃ is initiated only through the cycloaddition to the C?C bond, resulting in primary ozonide. The Arrhenius plot for most of the addition reaction shows positive temperature dependence, while for the abstraction reaction, it exhibits negative temperature dependence over the temperature range of 278–350 K. The calculated theoretical rate constants are in good agreement with available experimental data. Overall, the addition of both OH radical and ozone possesses ability to degrade MeSA, but slower when compared with the Cl radical. Copyright © 2015 John Wiley & Sons, Ltd.     

Analysis and Characterization of Microwave Irradiation–Induced Graft Copolymerization of Methyl Methacrylate onto Delignified Grewia Optiva Fiber

Grafting of methyl methacrylate (MMA) onto delignified Grewia optiva fiber using ascorbic acid/H₂O₂ as an initiator was carried out under microwave irradiation. The effects of varying the microwave power, exposure time, and concentration of initiator and monomer of graft polymerization were studied to obtain maximum grafting percentage (26.54%). The experimental results showed that the optimal conditions for grafting were: exposure time, 10min; microwave power, 110 W; ascorbic acid concentration, 3.74mol/L × 10^?2; H₂O₂ concentration, 0.97mol/L × 10^?1; monomer concentration, 1.87mol/L × 10^?1. The graft copolymers were characterized by Fourier transform-infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA).     

Fabrication of flexible conducting thin films of copper-MWCNT from multi-component aqueous suspension by electrodeposition

Flexible thin films of metal–carbon nanotube (CNT) with densely populated CNT morphology were fabricated by electrodeposition from an optimized copper bath. The substrate used for the present work is polyethylene film that was pre-deposited with electroless copper as a seed layer before CNT deposition. Optimum concentration of CNT was incorporated into copper bath and the electrodeposition was done at quiescent and agitation conditions. The bonding between the seed layer and the electrodeposited copper was good as revealed from adhesion test. Electrical as well as physical-mechanical property of the film was improved by CNT incorporation within the metal matrix. The topography and the texture of the metal–CNT deposit showed a well-refined structure as per scanning electron microscope (SEM), field emission scanning electron microscope (FE-SEM), and scanning probe microscope (SPM) analysis. The stability of the film was tested by cyclic voltammetric and stripping analysis under various applied conditions. Raman spectra and Fourier transfer infrared spectroscopic (FT-IR) analysis revealed the presence of CNT and the functionality of CNT within the copper matrix. Transmission electron microscope (TEM) analysis showed nucleation of copper on the surface of CNT walls.     

Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome,Boomerang Dysplasia,and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1–242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with FLNB variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of FLNB variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.     

A Comprehensive Review on Therapeutic Perspectives of Phytosterols in Insulin Resistance: A Mechanistic Approach

Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body’s healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.