• Udsen Joensen opublikował 1 rok, 3 miesiące temu

    32-0.69, p  less then  0.01), and not. The admission of patients classified as priority levels III/IV to ICU-RRT considerably jeopardized the admission of patients with priority levels I/II to these settings. The results found open new avenues for organizing public policies and improving ICU-RRT triage.A multiple receptor tyrosine kinase inhibitor, sunitinib, is a first-line therapy for clear cell renal cell carcinoma (CCRCC). Unfortunately, it has the major challenges of low initial response rate and resistance after about one year of treatment. Here we evaluated a microRNA (miRNA) and its target responsible for sunitinib resistance. Using miRNA profiling, we identified miR-96-5p upregulation in tumors from sunitinib-resistant CCRCC patients. By bioinformatic analysis, PTEN was selected as a potential target of miR-96-5p, which showed low levels in tumors from sunitinib-resistant CCRCC patients. Furthermore, PTEN and miR-96-5p levels were negatively correlated in a large The Cancer Genome Atlas kidney renal clear cell carcinoma cohort and high miR-96 and low PTEN represented poor prognosis in this cohort. Additionally, four-week sunitinib treatment increased miR-96-5p and decreased PTEN only in tumors from a sunitinib-resistant patient-derived xenograft model. We found a novel miR-96-5p binding site in the PTEN 3′ UTR and confirmed direct repression by luciferase reporter assay. Furthermore, we demonstrated that repression of PTEN by miR-96-5p increased cell proliferation and migration in sunitinib-treated cell lines. These results highlight the direct suppression of PTEN by miR-96-5p and that high miR-96-5p and low PTEN are partially responsible for sunitinib resistance and poor prognosis in CCRCC.Genetic Leukoencephalopathies (gLEs) are heritable white matter disorders that cause progressive neurological abnormalities. A founder mutation in the human endolysosomal trafficking protein VPS11 has been identified in Ashkenazi Jewish patients manifesting classic gLE symptoms of hypomyelination, developmental delay, motor and systemic deficits. In this study, we characterized the visual and sensorimotor function of two zebrafish vps11 mutant lines the previously reported vps11(plt), and a new vps11(-/-) null mutant line, using behavioral analysis to track larval motor responses to visual and acoustic stimuli. We found that mutant larvae from both vps11(plt) and vps11(-/-) lines were able to visually distinguish light and dark, but showed a progressive loss of a normal sensorimotor response to visual stimuli from 5 days post fertilization (dpf) to 7dpf. Additionally, optokinetic response analysis performed at 5dpf indicated that the mutants were significantly visually impaired. Both mutant lines also displayed a progressively lower sensorimotor response to a singular acoustic stimulus from 5-7dpf. Next, we tested the habituation response of the mutant lines to series of acoustic taps. We found both mutant lines habituated faster than their siblings, and that vps11(plt) mutants habituated faster than the vps11(-/-) mutants. Together, these data suggest that loss of Vps11 function results in progressive visual and sensorimotor abnormalities in the zebrafish vps11(plt) and vps11(-/-) mutant lines. This is the first study to characterize behavioral deficits in a vertebrate model of Vps11-dependent gLE. The mutants and behavioral assays described here could be a valuable model system in which to test potential pharmacological interventions for gLE.The threat of a nuclear attack has increased in recent years highlighting the benefit of developing additional therapies for the treatment of victims suffering from Acute Radiation Syndrome (ARS). In this work, we evaluated the impact of a PEGylated thrombopoietin mimetic peptide, JNJ-26366821, on the mortality and hematopoietic effects associated with ARS in mice exposed to lethal doses of total body irradiation (TBI). JNJ-26366821 was efficacious as a mitigator of mortality and thrombocytopenia associated with ARS in both CD2F1 and C57BL/6 mice exposed to TBI from a cobalt-60 gamma-ray source. Single administration of doses ranging from 0.3 to 1 mg/kg, given 4, 8, 12 or 24 h post-TBI (LD70 dose) increased survival by 30-90% as compared to saline control treatment. At the conclusion of the 30-day study, significant increases in bone marrow colony forming units and megakaryocytes were observed in animals administered JNJ-26366821 compared to those administered saline. In addition, enhanced recovery of FLT3-L levels was observed in JNJ-26366821-treated animals. Probit analysis of survival in the JNJ-26366821- and saline-treated cohorts revealed a dose reduction factor of 1.113 and significant increases in survival for up to 6 months following irradiation. These results support the potential use of JNJ-26366821 as a medical countermeasure for treatment of acute TBI exposure in case of a radiological/nuclear event when administered from 4 to 24 h post-TBI.The present research involves removing copper and nickel ions from synthesized wastewater by using a simple, cheap, cost-effective, and sustainable activated green waste tea residue (AGWTR) adsorption coupled with electrocoagulation (ADS/EC) process in the presence of iron electrodes. By considering previous studies, their adsorbents used for treating their wastewaters firstly activate them by applying either chemicals or activating agents. However, our adsorbent was prepared without applying neither chemicals nor any activating agents. The operating parameters such as pH, hydraulic retention time, adsorbent dose, initial concentration, current density, and operating cost for both metals were optimized. In ADS/EC, the removal efficiency was obtained as 100% for copper and 99.99% for nickel ions. After the ADS/EC process, Fourier transform infrared (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM) and Energy-dispersive X-ray spectroscopy (EDS) analysis were used to characterize the adsorbent green waste tea residue. The adsorption isotherm and kinetic model results showed that the Langmuir and the pseudo-second-order were well-fitted to the experimental adsorption data better than the Freundlich and pseudo-first-order models for both Cu2+ and Ni2+ with their maximum adsorption capacity of 15.6 and 15.9 mg g-1, respectively. The above results give an option to recycle the metal-based industrial effluents, tea industry-based wastes, enabling a waste-to-green technique for adsorbing and removing the heavy metals and other pollutants in water.As global water resources are decreasing and the demand for it is constantly increasing, the problem of proper water management is becoming more pressing. Poland is one of the largest producers of vegetables in Europe, including carrots, with significant exports. However its freshwater resources are relatively small. The paper presents the results of research on the water footprint (WF) life cycle assessment (LCA) in conventional and organic carrot production. The methodology of calculating WF was used in accordance with PN-EN ISO 14046. It was found, e.g., that WF for organic production of carrot (WF = 1.9 m3 ha-1) is over five times lower, as compared to conventional production (WF = 10.4 m3 ha-1). In the case of conventional production, the fertilization process (67.0-67.7%) has the greatest impact on the shaping of WF in the individual impact categories, i.e. Human Health, Ecosystem Quality and resources. In organic production, the WF-shaping factor is carrot harvesting (41.9-43.1%). The research can be used to develop pro-ecological carrot production technologies, as well as to shape sustainable development plans in agricultural areas. It can also be used to outline policy directions regarding foreign trade in water-consuming agricultural products.Better sensitivity of a biosensor could boost up the detection limit of analytes, thus a must in the fields of bio-sensing and bio-detection. To further enhance the sensitivity of a biosensor, in this work, we design an oblique-flat-sheet metamaterial perfect absorber (MPA) to concentrate the hot spots within air between the oblique flat sheet and the continuous ground metal, thus enabling fully interaction between analytes and hot spots. The corresponding field distributions in simulation corroborated our assumption and its sensitivity could be up to 1049 nm/RIU. Then, we fabricated the sample by e-beam lithography process for a seed layer and simply tilting the sample during deposition to obtain oblique flat sheets. When considering the stochastic nature of the deposited multiple oblique flat sheets, we modified the metallic upper resonator of the MPA from the single oblique-flat-sheet into randomly distributed oblique-wire-bundle (OWB) and in simulation, its sensitivity is boosted up to 3319 nm/RIU. In experiments, the measured sensitivity is 1329 nm/RIU under different concentrations of glucose solutions that is four times larger than the 330 nm/RIU of the planar MPA. The higher sensitivity was attributed to that the OWB MPA could provide hot spots within air not only between OWB and grounded metal but also among wires. Moreover, the OWB could also trap and concentrate the analytes locally.It is well known that azobenzene-containing polymers (azopolymers) are sensitive to the polarization orientation of the illuminating radiation, with the resulting photoisomerization inducing material transfer at both the meso- and macroscale. As a result, azopolymers are efficient and versatile photonic materials, for example, they are used for the fabrication of linear diffraction gratings, including subwavelength gratings, microlens arrays, and spectral filters. Here we propose to use carbazole-containing azopolymer thin films to directly visualize the longitudinal component of the incident laser beam, a crucial task for the realization of 3D structured light yet remaining experimentally challenging. We demonstrate the approach on both scalar and vectorial states of structured light, including higher-order and hybrid cylindrical vector beams. In addition to detection, our results confirm that carbazole-containing azopolymers are a powerful tool material engineering with the longitudinal component of the electric field, particularly to fabricate microstructures with unusual morphologies that differentiate from the total intensity distribution of the writing laser beam.Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants and children. The present study aimed to investigate the effects of miR-146a on RSV replication and the related mechanisms.

    We pretreated A549 and HEp-2 cells and young rats with miR-146a mimic before infection with RSV. The expressions of miR-146a and RSV-F mRNA in cells and lung tissues were detected by RT-qPCR, and production of IL-1β, IL-6, IL-18, and TNF-α in bronchial alveolar lavage fluid (BALF) were determined by ELISA. The expression level of TRAF-6 and activation of the JNK/ERK/MAPK/NF-κB signaling pathway was detected by Western blotting.

    RSV infection significantly reduced miR-146a levels in both A549 and HEp-2 cells and rat lung tissues. RSV infection resulted in accelerated growth, increased release of inflammatory cytokines, increased expression of TRAF-6, and activation of the JNK pathway in cells, and the lung inflammatory infiltration and the pathological score increased in rats. Overexpression of miR-146a targeted down-regulation of TRAF-6 expression and JNK/ERK/MAPK/NF-κB pathway induced by RSV infection, reduced the production of inflammatory cytokines IL-1β, IL-6 and TNF-α, and alleviate lung injury in young rats.

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