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In response to severe oxidative stress, Nrf2 induces Klf9 expression, which represses mtROS-eliminating enzymes to enhance cell death. Nrf2 is inactivated in certain pathological conditions, such as diabetes, but Keap1 down-regulation or mtROS elimination rescues Nrf2 expression and improves the pathology. These reports aid us in understanding the roles of Nrf2 in pathophysiological alterations involving mtROS.The Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/loss. Despite recent advances, little is known about the pathways involved in CZS pathogenesis. We performed a meta-analysis, gene ontology (GO), and pathway analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during hNPCs infection with ZIKV. We selected three studies (17 samples of infected hPNCs compared to hPNCs uninfected controls) through a systematic search of the Gene Expression Omnibus (GEO) database. The raw reads were trimmed, counted, and normalized. this website Next, we performed a rank product meta-analysis to detect consistently differentially expressed genes (DEGs) in these independent experiments. We detected 13 statistically significant DEGs. GO ontology and reactome analysis showed an enrichment of interferon, pro-inflammatory, and chemokines signaling and apoptosis pathways in ZIKV-infected cells. Moreover, we detected three possible new candidate genes involved in hNPCs infection APOL6, XAF1, and TNFRSF1. Our results confirm that interferon (IFN) signaling dominates the ZIKV response, and that a crucial contribution is given by apoptotic pathways, which might elicit the CZS phenotype.Protein-polysaccharide composites have been known to show a wide range of applications in biomedical and green chemical fields. These composites have been fabricated into a variety of forms, such as films, fibers, particles, and gels, dependent upon their specific applications. Post treatments of these composites, such as enhancing chemical and physical changes, have been shown to favorably alter their structure and properties, allowing for specificity of medical treatments. Protein-polysaccharide composite materials introduce many opportunities to improve biological functions and contemporary technological functions. Current applications involving the replication of artificial tissues in tissue regeneration, wound therapy, effective drug delivery systems, and food colloids have benefited from protein-polysaccharide composite materials. Although there is limited research on the development of protein-polysaccharide composites, studies have proven their effectiveness and advantages amongst multiple fields. This review aims to provide insight on the elements of protein-polysaccharide complexes, how they are formed, and how they can be applied in modern material science and engineering.In this study, we synthesized two main chain-type block copolymers featuring hydrogen bond donor and acceptor segments through atom transfer radical polymerization (ATRP) using a bifunctionalized polyhedral oligomeric silsesquioxane (POSS) nanoparticle as the initiator. Hydrosilylation of vinylbenzyl chloride at the two corners of a double-decker silsesquioxane (DDSQ) provided the bifunctionalized benzyl chloride initiator VBC-DDSQ-VBC, which we applied as a platform to prepare a main chain-type polystyrene homopolymer (PS-DDSQ-PS), the diblock copolymer poly(styrene-b-4-vinylpyridine) (P4VP-b-PS-DDSQ-PS-b-P4VP), and the diblock copolymer poly(styrene-b-tert-butoxystyrene) (PtBuOS-b-PS-DDSQ-PS-b-PtBuOS) through sequential ATRP. Selective hydrolysis of the tert-butoxyl units of PtBuOS-b-PS-DDSQ-PS-b-PtBuOS yielded the strongly hydrogen bonding diblock copolymer poly (styrene-b-vinylphenol) (PVPh-b-PS-DDSQ-PS-b-PVPh). We used Fourier transfer infrared spectroscopy, nuclear magnetic resonance spectroscopy, size exclusion chromatography, differential scanning calorimetry, mass-analyzed laser desorption ionization mass spectrometry, and transmission electron microscopy to investigate the chemical structures, thermal behavior, and self-assembled nanostructures formed by these main chain-type block copolymers based on DDSQ.Current anti-trypanosomal therapies suffer from problems of longer treatment duration, toxicity and inadequate efficacy, hence there is a need for safer, more efficacious and 'easy to use' oral drugs. Previously, we reported the discovery of the triazolopyrimidine (TP) class as selective kinetoplastid proteasome inhibitors with in vivo efficacy in mouse models of leishmaniasis, Chagas Disease and African trypanosomiasis (HAT). For the treatment of HAT, development compounds need to have excellent penetration to the brain to cure the meningoencephalic stage of the disease. Here we describe detailed biological and pharmacological characterization of triazolopyrimidine compounds in HAT specific assays. The TP class of compounds showed single digit nanomolar potency against Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense strains. These compounds are trypanocidal with concentration-time dependent kill and achieved relapse-free cure in vitro. Two compounds, GNF6702 and a new analog NITD689, showed favorable in vivo pharmacokinetics and significant brain penetration, which enabled oral dosing. They also achieved complete cure in both hemolymphatic (blood) and meningoencephalic (brain) infection of human African trypanosomiasis mouse models. Mode of action studies on this series confirmed the 20S proteasome as the target in T. brucei. These proteasome inhibitors have the potential for further development into promising new treatment for human African trypanosomiasis.Facial expression recognition has been well studied for its great importance in the areasof human-computer interaction and social sciences. With the evolution of deep learning, therehave been significant advances in this area that also surpass human-level accuracy. Althoughthese methods have achieved good accuracy, they are still suffering from two constraints (high computational power and memory), which are incredibly critical for small hardware-constrained devices. To alleviate this issue, we propose a new Convolutional Neural Network (CNN) architecture eXnet (Expression Net) based on parallel feature extraction which surpasses current methodsin accuracy and contains a much smaller number of parameters (eXnet 4.57 million, VGG1914.72 million), making it more efficient and lightweight for real-time systems. Several moderndata augmentation techniques are applied for generalization of eXnet; these techniques improvethe accuracy of the network by overcoming the problem of overfitting while containing the same size.
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