Notes

Image-based computerized Pores and skin Region Severity Catalog credit scoring through Convolutional Nerve organs Cpa networks.
© 2020 WILEY-VCH Verlag GmbH & Co. OSI-774 KGaA, Weinheim.Much effort within the nanosafety field is currently focused on the use of advanced in vitro models to reduce the gap between in vitro and in vivo studies. Within this context, precision-cut tissue slices are a unique ex vivo model to investigate nanoparticle impact using live tissue from laboratory animals and even humans. However, several aspects of the basic mechanisms of nanoparticle interactions with tissue have not yet been elucidated. To this end, liver slices are exposed to carboxylated and amino-modified polystyrene known to have a different impact on cells. As observed in standard cell cultures, amino-modified polystyrene nanoparticles induce apoptosis, and their impact is affected by the corona forming on their surface in biological fluids. Subsequently, a detailed time-resolved study of nanoparticle uptake and distribution in the tissue is performed, combining fluorescence imaging and flow cytometry on cells recovered after tissue digestion. As observed in vivo, the Kupffer cells accumulate high nanoparticle amounts and, interestingly, they move within the tissue towards the slice borders. Similar observations are reproduced in liver slices from human tissue. Thus, tissue slices can be used to reproduce ex vivo important features of nanoparticle outcomes in the liver and study nanoparticle impact on real tissue. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Immunotherapy is revolutionizing the treatment paradigm for a broad spectrum of malignancies. However, the immune checkpoint inhibitors also cause a unique set of toxicities. In the digestive system, this has consisted for the most part as colitis and hepatotoxicity, but also include less-common manifestations. Baseline screening, early identification, timely diagnosis, rapid and adequate treatment can significantly minimize the toxicity of immunotherapy and improve prognosis. This article provides a comprehensive review of gastrointestinal and hepatic immune-related toxicities, including incidence, mechanism, clinical manifestation, diagnosis, treatment, and guidelines for resumption of immune checkpoint inhibitor therapy. © 2020 John Wiley & Sons Australia, Ltd.Circular RNAs (circRNAs) have been identified in diverse cancers for their role in regulating multiple cellular processes by antagonizing microRNAs (miRNAs or miRs). However, the role of circRNA hsa_circ_0000092 in hepatocellular carcinoma (HCC) still remains enigmatic. Therefore, we aimed to investigate the specific mechanism of hsa_circ_0000092 in HCC. Differentially expressed circRNAs associated to HCC were initially analysed. The expression of hsa_circ_0000092, miR-338-3p and HN1 in HCC tissues and cell lines was examined. Next, the interaction among hsa_circ_0000092, miR-338-3p and HN1 was determined by dual-luciferase reporter, RNA pull-down and northern blot assays. Subsequently, a series of mimic, inhibitor or siRNA plasmids were delivered into HCC cells to validate the effects of hsa_circ_0000092, miR-338-3p and HN1 in controlling cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, the role of hsa_circ_0000092 in tumour growth of HCC in vivo was assessed with hsa_circ_0000092 depleted with siRNA. The hsa_circ_0000092/miR-338-3p/HN1 axis was predicted to participate in the development of HCC. hsa_circ_0000092 and HN1 were highly expressed while miR-338-3p was poorly expressed in HCC tissues and cell lines. hsa_circ_0000092 could competitively bind to miR-338-3p to up-regulate HN1 expression. Moreover, depleted hsa_circ_0000092 or elevated miR-338-3p was shown to suppress HCC cell proliferation, migration, invasion and angiogenesis in vitro via down-regulation of HN1. Furthermore, silencing hsa_circ_0000092 was demonstrated to suppress tumour growth in HCC in vivo. The results of this study suggested that hsa_circ_0000092 impaired miR-338-3p-mediated HN1 inhibition to aggravate the development of HCC, indicating that hsa_circ_0000092 is a potential candidate marker and therapeutic target for HCC. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.Critical to the development of all-solid-state lithium-ion batteries technology are novel solid-state electrolytes with high ionic conductivity and robust stability under inorganic solid-electrolyte operating conditions. Herein, by using density functional theory and molecular dynamics, a mixed oxygen-sulfur-based Li-superionic conductor is screened out from the local chemical structure of β-Li3 PS4 to discover novel Li14 P2 Ge2 S8 O8 (LPGSO) with high ionic conductivity and high stability under thermal, moist, and electrochemical conditions, which causes oxygenation at specific sites to improve the stability and selective sulfuration to provide an O-S mixed path by Li-S/O structure units with coordination number between 3 and 4 for fast Li-cooperative conduction. Furthermore, LPGSO exhibits a quasi-isotropic 3D Li-ion cooperative diffusion with a lesser migration barrier (≈0.19 eV) compared to its sulfide-analog Li14 P2 Ge2 S16 . The theoretical ionic conductivity of this conductor at room temperature is as high as ≈30.0 mS cm-1 , which is among the best in current solid-state electrolytes. Such an oxy-sulfide synergistic effect and Li-ion cooperative migration mechanism would enable the engineering of next-generation electrolyte materials with desirable safety and high ionic conductivity, for possible application in the near future. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Multivalent nanoparticle binding to cells can be of picomolar avidity making such interactions almost as intense as those seen with antibodies. However, reducing nanoparticle design exclusively to avidity optimization by the choice of ligand and its surface density does not sufficiently account for controlling and understanding cell-particle interactions. Cell uptake, for example, is of paramount significance for a plethora of biomedical applications and does not exclusively depend on the intensity of multivalency. In this study, it is shown that the mobility of ligands tethered to particle surfaces has a substantial impact on particle fate upon binding. Nanoparticles carrying angiotensin-II tethered to highly mobile 5 kDa long poly(ethylene glycol) (PEG) chains separated by ligand-free 2 kDa short PEG chains show a superior accumulation in angiotensin-II receptor type 1 positive cells. In contrast, when ligand mobility is constrained by densely packing the nanoparticle surface with 5 kDa PEG chains only, cell uptake decreases by 50%. Remarkably, irrespective of ligand mobility and density both particle types have similar EC50 values in the 1-3 × 10-9 m range. These findings demonstrate that ligand mobility on the nanoparticle corona is an indispensable attribute to be considered in particle design to achieve optimal cell uptake via multivalent interactions. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly-CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly-CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly-CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics analysis demonstrates that Gly-CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly-CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly-CDs. The integrated results demonstrate that Gly-CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Polyethylene glycols are synthetic polymers composed of repeating oxyethylene subunits, which have been known for non-toxic, non-immunogenic, non-antigenic, good solubility in water and therefore approved for pharmaceutical applications. Recently, attachment or amalgamation of polyethylene glycols to therapeutic small molecules, peptides, proteins, or nanoparticles has become a mature technology for the sake of improving their pharmacokinetic and pharmacological profiles, also referred to as PEGylation. By comparison, there are only a few PEGylated pharmaceuticals have been registered for further clinical trials and even less was approved for marketing. High failure rate of PEGylated pharmaceuticals in pre-clinical and clinical trials could be majorly attributed to their unclear pharmacokinetic behaviors. Therefore, the in vivo fate of the PEGylated pharmaceuticals for the various routes of administration needs to be thoroughly investigated An accurate in vivo pharmacological study thereof highly depends on the precise detection of polyethylene glycols as well as their fragments in biological matrixes. The goal of this review is to highlight the analytical methods that were developed and applied to evaluate the polyethylene glycols in pharmaceutical ingredients and excipients, which bring us closer to bridging the gap between the development of polyethylene glycol-based drug delivery systems and their clinical application. link2 © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Despite the ecological and economic significance of stony corals (Scleractinia), a robust understanding of their phylogeny remains elusive due to patchy taxonomic and genetic sampling, as well as the limited availability of informative markers. link3 To increase the number of genetic loci available for phylogenomic analyses in Scleractinia, we designed 15,919 DNA enrichment baits targeting 605 orthogroups (mean 565 ± SD 366 bp) over 1,139 exon regions. A further 236 and 62 barcoding baits were designed for COI and histone H3 genes respectively for quality and contamination checks. Hybrid capture using these baits was performed on 18 coral species spanning the presently understood scleractinian phylogeny, with two corallimorpharians as outgroup. On average, 74% of all loci targeted were successfully captured for each species. Barcoding baits were matched unambiguously to their respective samples and revealed low levels of cross-contamination in accordance with expectation. We put the data through a series of stringent filtering steps to ensure only scleractinian and phylogenetically informative loci were retained, and the final probe set comprised 13,479 baits, targeting 452 loci (mean 531 ± SD 307 bp) across 865 exon regions. Maximum likelihood, Bayesian and species tree analyses recovered maximally supported, topologically congruent trees consistent with previous phylogenomic reconstructions. The phylogenomic method presented here allows for consistent capture of orthologous loci among divergent coral taxa, facilitating the pooling of data from different studies and increasing the phylogenetic sampling of scleractinians in the future. This article is protected by copyright. All rights reserved.
Here's my website: https://www.selleckchem.com/products/Erlotinib-Hydrochloride.html