Gadegaardlancaster5138

Gene therapy research has advanced to clinical trials, but it is hampered by unstable nucleic acids packaged inside carriers and there is a lack of specificity towards targeted sites in the body. This study aims to address gene therapy limitations by encapsidating a plasmid synthesizing a short hairpin RNA (shRNA) that targets the anti-apoptotic Bcl-2 gene using truncated hepatitis B core antigen (tHBcAg) virus-like particle (VLP). A shRNA sequence targeting anti-apoptotic Bcl-2 was synthesized and cloned into the pSilencer 2.0-U6 vector. Tezacaftor in vitro The recombinant plasmid, namely PshRNA, was encapsidated inside tHBcAg VLP and conjugated with folic acid (FA) to produce FA-tHBcAg-PshRNA VLP. Electron microscopy revealed that the FA-tHBcAg-PshRNA VLP has an icosahedral structure that is similar to the unmodified tHBcAg VLP. Delivery of FA-tHBcAg-PshRNA VLP into HeLa cells overexpressing the folate receptor significantly downregulated the expression of anti-apoptotic Bcl-2 at 48 and 72 h post-transfection. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay demonstrated that the cells' viability was significantly reduced from 89.46% at 24 h to 64.52% and 60.63%, respectively, at 48 and 72 h post-transfection. As a conclusion, tHBcAg VLP can be used as a carrier for a receptor-mediated targeted delivery of a therapeutic plasmid encoding shRNA for gene silencing in cancer cells.A novel integrated sensor for the simultaneous measurement of layer refractive index and thickness based on evanescent fields is proposed. The theoretical limits for the accuracy of the sensor were examined for the example of a TiO2 layer. The influence of production tolerance on the accuracy was evaluated. In the experimental part of this work, a sensor chip containing nanowire and nanorib waveguides realized in silicon on insulator technology was used to demonstrate the detection of refractive index and thickness of a TiO2 atomic layer deposition (ALD) layer.The set of measures to contain the diffusion of COVID-19 instituted by the European governments gave an unparalleled opportunity to improve our understanding of the transport and industrial sectors' contribution to urban air pollution. The purpose of this study was to assess the impacts of the lockdown measures on air quality and pollutant emissions in Valencia, Spain. For this reason, we determined if there was a significant difference in the concentration levels of different particulate matter (PM) sizes, PM10, PM2.5, and NOx, NO2, NO, and O3, between the period of restrictions in 2020 and the same period in 2019. Our findings indicated that PM pollutant levels during the lockdown period were significantly different from the same period of the previous year, even if there is variability in the different local areas. The highest variations reduction in the PM10 and PM2.5 levels were observed for the València Centre, València Avd Francia, and València Pista de Silla (all of the urban traffic type) in which there was a reduction of 58%-42%, 56%-53%, and 60%-41% respectively. Moreover, consistent with recent studies, we observed a significant reduction in nitric oxide levels in all the air monitoring stations. In all seven monitoring stations, it was observed, in 2020, NOx, NO2, and NO concentrations decreased by 48.5%-49.8%-46.2%, 62.1%-67.4%-45.7%, 37.4%-35.7%-35.3%, 60.7%-67.7%-47.1%, 65.5%-65.8%-63.5%, 60.0%-64.5%-41.3%, and 60.4%-61.6%-52.5%, respectively. Lastly, overall O3 levels decreased during the lockdown period, although this phenomenon was more closely related to weather conditions. Overall, no significant differences were observed between the meteorological conditions in 2019 and 2020. Our findings suggest that further studies on the effect of human activities on air quality are needed and encourage the adoption of a holistic approach to improve urban air quality.Background and Objectives The prognosis of metastatic or unresectable gastric cancer is dismal, and the benefits of the palliative resection of primary tumors with noncurative intent remain controversial. This study aimed to evaluate the impact of palliative gastrectomy (PG) on overall survival in gastric cancer patients. Materials and Methods One hundred forty-eight gastric cancer patients who underwent PG or a nonresection (NR) procedure between January 2011 and 2017 were retrospectively reviewed to select and analyze clinicopathological factors that affected prognosis. Results Fifty-five patients underwent primary tumor resection with palliative intent, and 93 underwent NR procedures owing to the presence of metastatic or unresectable disease. The PG group was younger and more female dominant. In the PG group, R1 and R2 resection were performed in two patients (3.6%) and 53 patients (96.4%), respectively. The PG group had a significantly longer median overall survival than the NR group (28.4 vs. 7.7 months, p less then 0.001). Multivariate analyses revealed that the overall survival was significantly better after palliative resection (hazard ratio (HR), 0.169; 95% confidence interval (CI), 0.088-0.324; p less then 0.001) in patients with American Society of Anesthesiologists Physical Status (ASA) scores ≤1 (HR, 0.506; 95% CI, 0.291-0.878; p = 0.015) and those who received postoperative chemotherapy (HR, 0.487; 95% CI, 0.296-0.799; p = 0.004). Among the patients undergoing palliative resection, the presence of less then 15 positive lymph nodes was the only significant predictor of better overall survival (HR, 0.329; 95% CI, 0.121-0.895; p = 0.030). Conclusions PG might lead to the prolonged survival of certain patients with incurable gastric cancer, particularly those with less-extensive lymph-node metastasis.In this work, the fracture mechanics properties of polyamide (PA) specimens manufactured by the selective laser sintering (SLS) technology are investigated, in which an embedded crack-like notch was inserted in the design and produced during the additive manufacturing (AM) phase. To cover a wide variety of mode I/II mixity levels, the inclined asymmetrical semicircular specimen subjected to three points loading (IASCB) was employed. The investigation was carried out by analyzing the full displacement field in the proximity of the crack tip by means of the digital image correlation (DIC) technique. To characterize the material, which exhibits a marked elastic-plastic behavior, the quantity J-integral was evaluated by two different methods the first one exploits the full fields measured by the DIC, whereas the second one exploits the experimental load-displacement curves along with FEM analysis. The DIC methodology was experimentally validated and proposed as an alternative method to evaluate the J-integral. It is especially suited for conditions in which it is not possible to use the conventional LDC method due to complex and possibly unknown loading conditions.