Friend or Foe? Revising the Role of Oxygen in the Tribological Performance of Solid Lubricant MoS2.

Molybdenum disulfide (MoS2) is a solid lubricant used in various forms, such as a dry lubricant by itself or as a component of a more complex coating. In both these forms, the effect of oxygen contamination on the sliding properties of the MoS2 coatings is traditionally considered detrimental, resulting in expensive technological processes to produce pure MoS2. Here, it is shown that the high oxygen content does not necessarily hinder the solid lubricant properties and may even result in a lower friction and wear when compared to pure MoS2. Mo-S-O coatings were fabricated by unbalanced magnetron sputtering and tribologically tested under vacuum conditions. Oxygen caused amorphization of the as-deposited coatings but did not prevent the triboactivated formation of an ultra-thin crystalline MoS2 tribolayer with the incorporated oxygen. Such an imperfect tribolayer was found to reduce the coefficient of friction to 0.02, a value lower than that of pure MoS2. Moreover, owing to the higher density and hardness of oxygen-containing films, the wear rate was also found to be lower. Molecular dynamics simulations performed using a newly developed Mo-S-O force field confirmed that such an imperfect tribolayer can mitigate friction in a manner comparable to that of MoS2.

Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules.

The phosphodiesterase (PDE) enzymes, key regulator of the cyclic nucleotide signal transduction system, are long-established as attractive therapeutic targets. During investigation of trends within clinical trials, we have identified a particularly high number of clinical trials involving PDE inhibitors, prompting us to further evaluate the current status of this class of therapeutic agents. In total, we have identified 87 agents with PDE-inhibiting capacity, of which 85 interact with PDE enzymes as primary target. We provide an overview of the clinical drug development with focus on the current clinical uses, novel molecules and indications, highlighting relevant clinical studies. We found that the bulk of current clinical uses for this class of therapeutic agents are chronic obstructive pulmonary disease (COPD), vascular and cardiovascular disorders and inflammatory skin conditions. In COPD, particularly, PDE inhibitors are characterised by the compliance-limiting adverse reactions. We discuss efforts directed to appropriately adjusting the dose regimens and conducting structure-activity relationship studies to determine the effect of structural features on safety profile. The ongoing development predominantly concentrates on central nervous system diseases, such as schizophrenia, Alzheimer's disease, Parkinson's disease and fragile X syndrome; notable advancements are being also made in mycobacterial infections, HIV and Duchenne muscular dystrophy. Our analysis predicts the diversification of PDE inhibitors' will continue to grow thanks to the molecules in preclinical development and the ongoing research involving drugs in clinical development.

Analysis of the interaction of seeds with a centrifugal disk working body of a chamber-type treater.

Presowing seed treatment is the first step in growing crops and obtaining a predicted high-quality yield. It plays a vital role in an integrated plant protection system. When treating seeds before sowing, it is crucial to avoid seed damage by the machine working bodies to obtain the planned harvest. For that reason, when designing new machines, it is necessary to exclude the use of auger working bodies and reduce the treatment speed. This paper analyzes the interaction of seeds with the working surfaces of centrifugal disk distribution bodies of pressown seed treatment machines. This paper considers the influence of geometric and kinematic factors on the distribution of particles at the outlet of the disk working body. Theoretical dependences that allow determining the relative speed of seed escape from the blades of a centrifugal disk have been obtained. An experimental plant allowing testing of the effectiveness of the proposed technical solution has been designed and manufactured. Theoretical and experimental studies allowed us to determine the conditions necessary for uniform chemical treatment of seeds and reduce the impact of centrifugal-type working bodies on seeds when treated with chemical or biological preparations before sowing.

Recent developments of HDAC inhibitors: Emerging indications and novel molecules.

The histone deacetylase (HDAC) enzymes, a class of epigenetic regulators, are historically well established as attractive therapeutic targets. During investigation of trends within clinical trials, we have identified a high number of clinical trials involving HDAC inhibitors, prompting us to further evaluate the current status of this class of therapeutic agents. In total, we have identified 32 agents with HDAC-inhibiting properties, of which 29 were found to interact with the HDAC enzymes as their primary therapeutic target. In this review, we provide an overview of the clinical drug development highlighting the recent advances and provide analysis of specific trials and, where applicable, chemical structures. We found haematologic neoplasms continue to represent the majority of clinical indications for this class of drugs; however, it is clear that there is an ongoing trend towards diversification. Therapies for non-oncology indications including HIV infection, muscular dystrophies, inflammatory diseases as well as neurodegenerative diseases such as Alzheimer's disease, frontotemporal dementia and Friedreich's ataxia are achieving promising clinical progress. Combinatory regimens are proving to be useful to improve responsiveness among FDA-approved agents; however, it often results in increased treatment-related toxicities. This analysis suggests that the indication field is broadening through a high number of clinical trials while several fields of preclinical development are also promising.

The Long-Term Effect of Medically Enhancing Melanin Intrinsic Bioenergetics Capacity in Prematurity.

BACKGROUND: The ability of the human body to produce metabolic energy from light modifies fundamental concepts of biochemistry. OBJECTIVE: This review discusses the relationships between the long-accepted concept is that glucose has a unique dual role as an energy source and as the main source of carbon chains that are precursors of all organic matter. The capability of melanin to produce energy challenges this premise. METHODS: The prevalent biochemical concept, therefore, needs to be adjusted to incorporate a newly discovered state of Nature based on melanin's ability to dissociate water to produce energy and to re-form water from molecular hydrogen and oxygen. RESULTS AND DISCUSSION: Our findings regarding the potential implication of QIAPI-1 as a melanin precursor that has bioenergetics capabilities. CONCLUSION: Specifically, we reported its promising application as a means for treating retinopathy of prematurity (ROP). The instant report focuses on the long-term treatment medical effects of melanin in treating ROP.

Pristine and Antibiotic-Loaded Nanosheets/Nanoneedles-Based Boron Nitride Films as a Promising Platform to Suppress Bacterial and Fungal Infections.

In recent years, bacteria inactivation during their direct physical contact with surface nanotopography has become one of the promising strategies for fighting infection. Contact-killing ability has been reported for several nanostructured surfaces, e.g., black silicon, carbon nanotubes, zinc oxide nanorods, and copper oxide nanosheets. Herein, we demonstrate that Gram-negative antibiotic-resistant Escherichia coli (E. coli) bacteria are killed as a result of their physical destruction while contacting nanostructured h-BN surfaces. BN films, made of spherical nanoparticles formed by numerous nanosheets and nanoneedles with a thickness <15 nm, have been obtained through a reaction of ammonia with amorphous boron. The contact-killing bactericidal effect of BN nanostructures has been compared with a toxic effect of gentamicin released from them. For a wider protection against bacterial and fungal infection, the films have been saturated with a mixture of gentamicin and amphotericin B. Such BN films demonstrate a high antibiotic/antimycotic agent loading capacity and a fast initial and sustained release of therapeutic agents for 170-260 h depending on the loaded dose. The pristine BN films possess high antibacterial activity against E. coli K-261 strain at their initial concentration of 104 cells/mL, attaining >99% inactivation of colony forming units after 24 h, same as gentamicin-loaded (150 µg/cm2) BN sample. The BN films loaded with a mixture of gentamicin (150 and 300 µg/cm2) and amphotericin B (100 µg/cm2) effectively inhibit the growth of E. coli K-261 and Neurospora crassa strains. During immersion in the normal saline solution, the BN film generates reactive oxygen species (ROS), which can lead to accelerated oxidative stress at the site of physical cell damage. The obtained results are valuable for further development of nanostructured surfaces having contact killing, ROS, and biocide release abilities.

Opportunities and challenges for drug discovery in modulating Adhesion G protein-coupled receptor (GPCR) functions.

INTRODUCTION: The G protein-coupled receptors (GPCR) superfamily is among the most widely exploited targets for therapeutics, with drugs mainly targeting the Rhodopsin, Glutamate and Secretin family receptors. The receptors of the Adhesion family, however, remain comparatively unexplored in this aspect. This review aims to discuss the druggability of Adhesion GPCRs (aGPCR), highlighting the relevant opportunities and challenges. AREAS COVERED: In this review, the authors provide a disease-oriented summary of aGPCR involvement in humans and discuss the current status of characterizing therapeutic agents with a focus on new opportunities using low molecular weight substances. EXPERT OPINION: The small molecule antagonist dihydromunduletone and partial agonist 3-α-acetoxydihydrodeoxygedunin, along with the endogenous natural ligand synaptamide currently comprise some of the most important discoveries made in an attempt to characterize aGPCR druggability. The small molecule modulators provide important insights regarding the structure-activity relationship and suggest that targeting the tethered peptide agonist results in a nonselective pharmacological action, while synaptamide may be considered a potentially attractive tool to achieve a higher degree of selectivity.

Knowledge, Attitudes and Practices (KAP) Relating to Dietary Supplements Among Health Sciences and Non-Health Sciences Students in One of The Universities of United Arab Emirates (UAE).

INTRODUCTION: The use of Dietary Supplements (DS) has increased substantially in the United Arab Emirates (UAE) in recent years, despite the fact that the efficacy and safety of these supplements are not proven yet. In addition, the practices of supplement users in the UAE remain undocumented. AIM: To determine the usage of DS in health sciences and non-health sciences students; and to determine their knowledge, attitudes and practices (KAP) regarding these supplements. MATERIALS AND METHODS: A descriptive, cross-sectional, questionnaire-based study was conducted among university students. Based on the Raosoft online calculator, it was anticipated that the sample of 383 students would enable us to achieve the study objectives. Students were recruited from Ajman University of Science and Technology and identified by the academic staff through students' records. All students who were registered at Ajman University of Science and Technology - including medical (i.e. dental, pharmacy and health sciences) and non-medical colleges (i.e. engineering, business administration, law, information technology, mass communications and humanities) - were invited to participate, after obtaining the approval of the Institutional Ethics Committee (IEC), (during the period of January-February 2015). This study used quantitative method approach. Therefore, data were analysed quantitatively using SPSS version 22.0. RESULTS: More than one-third of participants (39%) were found to consume DS. The most common reasons for consuming supplements were to maintain good health (58,21%) and ensure adequate nutrition (43,15%). Almost two-thirds of participants (65%) perceived that the best way to obtain nutrients is through food and DS together (49%), or DS alone (16%). Therefore, there was a relatively high amount of DS intake among participants in this study. With regard to medical and non-medical students' use of DS, there were no significant differences in the use (p=0.139). However, other findings suggest that there are significant differences in the knowledge of health sciences and non-health sciences students pertaining to the health benefits and safety of these supplements (p<0.001), what they are (p=0.040) and the source of help that should be sought when using them (p<0.001). CONCLUSION: There is a relatively high prevalence of DS consumption among students, which they reported as using to maintain good health and ensure adequate nutrition. However, findings suggest that there are significant differences in the knowledge of health sciences and non-health sciences students pertaining to the health benefits and safety of these supplements. Therefore, awareness of DS usage and information should be integrated into everyday practice.