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Of these patients, at least 93% of patients were prescribed anticholinergics, and 37% were prescribed dual therapy. Patients 65 years and older were more likely to initiate a new NDO medication at their visit (43%) than patients under 65 (7%). CONCLUSIONS This is the first study to analyze the use of medical therapy for NLUTD in a large outpatient setting. Further prospective evaluation of patient satisfaction and efficacy of both single anticholinergic medication and dual therapy is needed. © 2020 John Wiley & Sons Australia, Ltd.Virus-like nanoparticles (VLPs) have been used as an attractive means in cancer immunotherapy because of their unique intrinsic immunostimulatory properties. However, for treating metastatic tumors in the peritoneal cavity, such as ovarian cancer, multiple injections of therapy are needed due to the large peritoneal space and fast excretion of therapy. Here, it is reported on the development of active VLP delivery vehicles for the treatment of peritoneal ovarian tumors using biocompatible Qβ VLPs-loaded Mg-based micromotors. The autonomous propulsion of such Qβ VLPs-loaded Mg-micromotors in the peritoneal fluid enables active delivery of intact immunostimulatory Qβ VLPs to the peritoneal space of ovarian tumor bearing mice, greatly enhancing the local distribution and retention of Qβ VLPs. Such improved distribution and longer retention time of Qβ in the peritoneal cavity leads to enhanced immunostimulation and therefore increased survival rate of tumor-bearing mice compared to a passive Qβ treatment. For clinical translation, the active delivery of VLPs holds great promise for tumor immunotherapy toward the treatment of different types of primary and metastatic tumors in the peritoneal cavity. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND & AIMS Obesity is associated with non-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients with chronic liver disease of different aetiologies (eg HCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery. METHODS Two-hundred and twenty-six subjects (160 females; mean age 42.9 years ±10.8 SD) without evidence of any further cause of liver disease consecutively underwent bariatric surgery in two Italian liver centers. During surgery, all patients underwent liver biopsy for histological evaluation and molecular studies. Liver DNA extracts were tested for PNPLA3, TM6SF2, MBOAT7, IRGM polymorphisms and for OBI. Univariate and multivariate analyses were used to identify predictors of NASH. RESULTS Histology showed NASH in 115 (50.9%) and NAFL in 111 cases (49.1%). Twenty-nine/226 (12.8%) cases had OBI, 24 (82.8%) of whom had NASH and 5 (17.2%) NAFL, whereas among the 197 OBI-negative cases, 91 (46.2%) had NASH and 106 (53.8%) NAFL (P = .0002). Multivariate analysis showed that older age (P = .03, OR 1.034), alanine aminotransferase values (P = .005, OR 1.023), insulin resistance/diabetes (P = .02, OR 2.257), TM6SF2 polymorphism (P = .04, OR 3.168) and OBI (P = .004, OR 5.503) were independent predictors of NASH. CONCLUSION NASH is highly prevalent in obese individuals undergoing bariatric surgery. OBI is one of the strongest risk factors of NASH in these patients. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.The efficacy of current antiviral drugs used to treat influenza has been declining because of mutations and resistance of the virus. Herein, a light-sensitive multiligand architecture is developed consisting of chitosan conjugated to a photosensitizer and 6'-sialyllactose (SL) to develop an antiviral agent against influenza with a different mechanism of action (SL-chitosan-Chlorin e6, SCC). Saturation transfer difference-nuclear magnetic resonance determined that the ability of SCC to bind to viral hemagglutinin is stronger than that of the monomeric substance. Virus recognition is confirmed by immunofluorescence and transmission electron microscope imaging. SCC induces viral inactivation by causing permanent membrane damage through its photoactivity. Viral membrane is oxidized by the photoactivity of SCC, thus, the virus membrane collapses. Furthermore, using the plaque reduction assay to evaluate the inhibitory effect of SCC on influenza A and B, it is found that its antiviral effects are 23% and 50% higher than the conventional antiviral drug. Additionally, SCC prevents infection by influenza in 100% of mice subjected to laser irradiation. These results indicate that this photodynamic multiligand structure can overcome the limitations of existing antiviral agents and suggest a pertinent methodology of prophylaxis and treatment by preemptively attacking the virus before it enters the host cell. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIMS Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in NTDs has never been characterized. NOX4 is a potential target of miR-322, and we have previously demonstrated that miR-322 was involved in high glucose-induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism for miR-322 that disrupts neurulation by ameliorating cell apoptosis. METHODS All-trans-retinoic acid (ATRA)-induced mouse model was utilized to study NTDs. RNA pull-down and dual-luciferase reporter assays were used to confirm the interaction between NOX4 and miR-322. In mouse neural stem cells and whole-embryo culture, Western blot and TUNEL were carried out to investigate the effects of miR-322 and NOX4 on neuroepithelium apoptosis in NTD formation. RESULTS NOX4, as a novel target of miR-322, was upregulated in ATRA-induced mouse model of NTDs. In mouse neural stem cells, the expression of NOX4 was inhibited by miR-322; still further, NOX4-triggered apoptosis was also suppressed by miR-322. Moreover, in whole-embryo culture, injection of the miR-322 mimic into the amniotic cavity attenuated cell apoptosis in NTD formation by silencing NOX4. CONCLUSION miR-322/NOX4 plays a crucial role in apoptosis-induced NTD formation, which may provide a new understanding of the mechanism of embryonic NTDs and a basis for potential therapeutic target against NTDs. © 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.Numerous studies have demonstrated the in vitro and in vivo neurotoxicity of nanoparticulate titanium dioxide (nano-TiO2 ), a mass-produced material for a large number of commercial and industrial applications. The mechanism of nano-TiO2 -induced inhibition of axonal development, however, is still unclear. In our study, primary cultured hippocampal neurons of 24-hour-old fetal Sprague-Dawley rats were exposed to 5, 15, or 30 μg/mL nano-TiO2 for 6, 12, and 24 hours, and the toxic effects of nano-TiO2 exposure on the axons development were detected and its molecular mechanism investigated. Nano-TiO2 accumulated in hippocampal neurons and inhibited the development of axons as nano-TiO2 concentrations increased. Increasing time in culture resulted in decreasing axon length by 32.5%, 36.6%, and 53.8% at 6 hours, by 49.4%, 53.8%, and 69.5% at 12 hours, and by 44.5%, 58.2%, and 63.6% at 24 hours, for 5, 15, and 30 μg/mL nano-TiO2 , respectively. Furthermore, nano-TiO2 downregulated expression of Netrin-1, growth-associated protein-43, and Neuropilin-1, and promoted an increase of semaphorin type 3A and Nogo-A. These studies suggest that nano-TiO2 inhibited axonal development in rat primary cultured hippocampal neurons and this phenomenon is related to changes in the expression of axon growth-related factors. © 2020 Wiley Periodicals, Inc.The vascular network is a central component of the organ-on-a-chip system to build a 3D physiological microenvironment with controlled physical and biochemical variables. Inspired by ubiquitous biological systems such as leaf venation and circulatory systems, a fabrication strategy is devised to develop a biomimetic vascular system integrated with freely designed chambers, which function as niches for chamber-specific vascularized organs. As a proof of concept, a human-on-leaf-chip system with biomimetic multiscale vasculature systems connecting the self-assembled 3D vasculatures in chambers is fabricated, mimicking the in vivo complex architectures of the human cardiovascular system connecting vascularized organs. Besides, two types of vascularized organs are built independently within the two halves of the system to verify its feasibility for conducting comparative experiments for organ-specific metastasis studies in a single chip. Successful culturing of human hepatoma G2 cells (HepG2s) and mesenchymal stem cells (MSCs) with human umbilical vein endothelial cells (HUVECs) shows good vasculature formation, and organ-specific metastasis is simulated through perfusion of pancreatic cancer cells and shows distinct cancer encapsulation by MSCs, which is absent in HepG2s. Given good culture efficacy, study design flexibility, and ease of modification, these results show that the bioinspired human-on-leaf-chip possesses great potential in comparative and metastasis studies while retaining organ-to-organ crosstalk. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Magnetic-plasmonic nanoparticles have received considerable attention for widespread applications. These nanoparticles (NPs) exhibiting surface-enhanced Raman scattering (SERS) activities are developed due to their potential in bio-sensing applicable in non-destructive and sensitive analysis with target-specific separation. However, it is challenging to synthesize these NPs that simultaneously exhibit low remanence, maximized magnetic content, plasmonic coverage with abundant hotspots, and structural uniformity. Here, a method that involves the conjugation of a magnetic template with gold seeds via chemical binding and seed-mediated growth is proposed, with the objective of obtaining plasmonic nanostructures with abundant hotspots on a magnetic template. To obtain a clean surface for directly functionalizing ligands and enhancing the Raman intensity, an additional growth step of gold (Au) and/or silver (Ag) atoms is proposed after modifying the Raman molecules on the as-prepared magnetic-plasmonic nanoparticles. Importantly, one-sided silver growth occurred in an environment where gold facets are blocked by Raman molecules; otherwise, the gold growth is layer-by-layer. Moreover, simultaneous reduction by gold and silver ions allowed for the formation of a uniform bimetallic layer. The enhancement factor of the nanoparticles with a bimetallic layer is approximately 107 . PR-619 The SERS probes functionalized cyclic peptides are employed for targeted cancer-cell imaging and separation. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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