Autophagy,Unfolded Protein Response,and Neuropilin-1 Cross-Talk in SARS-CoV-2 Infection: What Can Be Learned from Other Coronaviruses

The COVID-19 pandemic is caused by the 2019–nCoV/SARS-CoV-2 virus. This severe acute respiratory syndrome is currently a global health emergency and needs much effort to generate an urgent practical treatment to reduce COVID-19 complications and mortality in humans. Viral infection activates various cellular responses in infected cells, including cellular stress responses such as unfolded protein response (UPR) and autophagy, following the inhibition of mTOR. Both UPR and autophagy mechanisms are involved in cellular and tissue homeostasis, apoptosis, innate immunity modulation, and clearance of pathogens such as viral particles. However, during an evolutionary arms race, viruses gain the ability to subvert autophagy and UPR for their benefit. SARS-CoV-2 can enter host cells through binding to cell surface receptors, including angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1). ACE2 blockage increases autophagy through mTOR inhibition, leading to gastrointestinal complications during SARS-CoV-2 virus infection. NRP1 is also regulated by the mTOR pathway. An increased NRP1 can enhance the susceptibility of immune system dendritic cells (DCs) to SARS-CoV-2 and induce cytokine storm, which is related to high COVID-19 mortality. Therefore, signaling pathways such as mTOR, UPR, and autophagy may be potential therapeutic targets for COVID-19. Hence, extensive investigations are required to confirm these potentials. Since there is currently no specific treatment for COVID-19 infection, we sought to review and discuss the important roles of autophagy, UPR, and mTOR mechanisms in the regulation of cellular responses to coronavirus infection to help identify new antiviral modalities against SARS-CoV-2 virus.     

Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer

Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment.     

Water swellable rubber composites: An update review from preparation to properties

In recent years, water swellable rubber composites have been the subject of many scientific and research investigations as well as many industrial programs. Here, we present an updated overview of the developments in the area of water swellable rubber composites with different kinds of fillers, compatibilizers, and cross‐linked agents, in terms of their manufacturing methods, synthesis, chemical, physical, and mechanical properties. Several critical issues and suggestions for future work are detailed, underscoring the roles of material scientists and manufacturing engineers in the bright future of this new material through value addition to enhance its usage and fields of application. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42786.     

Spectrophotometric and chemometric studies on the simultaneous determination of two benzodiazepines in human plasma

A numerical simple, accurate and precise method based on spectrophotometric data coupled with multivariate calibration methods, PLS and MLR, combined with GA was developed for the simultaneous determination of two benzodiazepines, Clobazam and Flurazepam. A data set of absorption spectra obtained from a calibration set of mixtures containing the compounds was used to build GA-PLS and GA-MLR models. The models were tested using a dataset constructed from the compound synthetic solutions. The better model was also applied to plasma samples. The proposed method requires no preliminary separation steps and can be used for these drugs analysis in quality control laboratories.     

Overcoming endogenous constraints on neuronal regeneration

One of the grand challenges in neuroengineering is to stimulate regeneration after central nervous system (CNS) or peripheral nervous system (PNS) injury to restore function. The state of the art today is that PNS injuries heal to a limited extent, whereas CNS injuries are largely intractable to regeneration. In this context, we examine the underlying biochemical and cellular constraints on endogenous healing of neural tissues. Identification and characterization of endogenous "rate-limiting" processes that constrain regeneration would allow one to craft solutions to overcome critical impediments for accelerated healing. It is increasingly evident that biochemical pathways triggered by the nature and duration of injury-triggered inflammatory response may determine the endogenous constraints and subsequently determine regenerative fate. In this paper, critical endogenous constraints of PNS and CNS regeneration are identified, and the effects of modulating the phenotypes of immune cells on neuronal regeneration are discussed.     

Effects of Kenaf core on properties of poly(lactic acid) bio‐composite

In this study, biodegradable poly(lactic acid) (PLA)/Kenaf core composites with different amount of Kenaf core were prepared using screw extrusion. The Structure, thermal stability, mechanical properties, and biodegradation of bio‐composites are evaluated. FTIR result shows the possible interaction between the Ken core and PLA matrix. The FESEM result showed that Kenaf core was uniformly disperse in PLA matrix. Tensile and flexural strength of PLA was improved Up to the 30%vol of kenaf core content. Young's modulus and hardness properties were improved by adding kenaf core into PLA matrix. Bio‐composite density has been decreased by adding more kenaf core and water absorption of the compound was increased linear. High Kenaf core content was also found to increase the rate of biodegradability of PLA/kenaf core. It can be proven by exposure of the samples to the environment and weight loss in soil burial analysis. POLYM. COMPOS., 35:1220–1227, 2014. © 2013 Society of Plastics Engineers     

Self-assembled targeted nanoparticles: evolution of technologies and bench to bedside translation

Nanoparticles (NPs) have become an important tool in many industries including healthcare. The use of NPs for drug delivery and imaging has introduced exciting opportunities for the improvement of disease diagnosis and treatment. Over the past two decades, several first-generation therapeutic NP products have entered the market. Despite the lack of controlled release and molecular targeting properties in these products, they improved the therapeutic benefit of clinically validated drugs by enhancing drug tolerability and/or efficacy. NP-based imaging agents have also improved the sensitivity and specificity of different diagnostic modalities. The introduction of controlled-release properties and targeting ligands toward the development of next-generation NPs should enable the development of safer and more effective therapeutic NPs and facilitate their application in theranostic nanomedicine. Targeted and controlled-release NPs can drastically alter the pharmacological characteristics of their payload, including their pharmacokinetic and, in some cases, their pharmacodynamic properties. As a result, these NPs can improve drug properties beyond what can be achieved through classic medicinal chemistry. Despite their enormous potential, the translation of targeted NPs into clinical development has faced considerable challenges. One significant problem has been the difficulty in developing targeted NPs with optimal biophysicochemical properties while using robust processes that facilitate scale-up and manufacturing. Recently, efforts have focused on developing NPs through self-assembly or high-throughput processes to facilitate the development and screening of NPs with these distinct properties and the subsequent scale-up of their manufacture. We have also undertaken parallel efforts to integrate additional functionality within therapeutic and imaging NPs, including the ability to carry more than one payload, to respond to environmental triggers, and to provide real-time feedback. In addition, novel targeting approaches are being developed to enhance the tissue-, cell-, or subcellular-specific delivery of NPs for a myriad of important diseases. These include the selection of internalizing ligands for enhanced receptor-mediated NP uptake and the development of extracellular targeting ligands for vascular tissue accumulation of NPs. In this Account, we primarily review the evolution of marketed NP technologies. We also recount our efforts in the design and optimization of NPs for medical applications, which formed the foundation for the clinical translation of the first-in-man targeted and controlled-release NPs (BIND-014) for cancer therapy.     

A metadata model for collaborative experiments and simulations in earthquake engineering

Research projects in earthquake engineering yield a very large amount of complex data from experiments and computer simulations. Understanding and exchanging these complicated and voluminous data sets prompted the development of metadata models that document the processes of data generation, and facilitate the collaboration and exchange of information between researchers. The present metadata model was designed to document and exchange a large number of large data files in earthquake engineering, but is applicable to other fields of engineering and science. The model was conceived based on a series of former data models, which were unduly complicated and limited to few types of experiments. Simpler than its predecessors, the present metadata model applies to all kinds of earthquake engineering experiments. It was developed in the object-oriented framework using Protégé. Its applications are illustrated with examples from centrifuge experiments.     

A new PSO-based algorithm for multi-objective optimization with continuous and discrete design variables

This paper presents a new multi-objective optimization algorithm called FC-MOPSO for optimal design of engineering problems with a small number of function evaluations. The proposed algorithm expands the main idea of the single-objective particle swarm optimization (PSO) algorithm to deal with constrained and unconstrained multi-objective problems (MOPs). FC-MOPSO employs an effective procedure in selection of the leader for each particle to ensure both diversity and fast convergence. Fifteen benchmark problems with continuous design variables are used to validate the performance of the proposed algorithm. Finally, a modified version of FC-MOPSO is introduced for handling discrete optimization problems. Its performance is demonstrated by optimizing five space truss structures. It is shown that the FC-MOPSO can effectively find acceptable approximations of Pareto fronts for structural MOPs within very limited number of function evaluations.