Buckrollins1959
Plant cell imaging is critical for agricultural production and plant pathology study. Advanced upconversion nanoparticles (UCNPs) are being developed as fluorescent probes for imaging cells and tissues in vivo and in vitro. Unfortunately, the thick cellulosic walls as barriers together with hemicelluloses and pectin hinder the entrance of macromolecules into the epidermal plant cell. Hence, realizing satisfactory temporal and spatial resolution with UCNPs remains an arduous task. Here, bipyramidal LiErF41%Tm3+@LiYF4 core-shell UCNPs with a super-bright red emission upon 980 nm laser excitation are explored, where the introduction of Tm3+ ions permits alleviation of the energy loss at defective sites and a significant improvement of the upconversion output. The as-obtained bipyramidal UCNPs could readily puncture plant cell walls and further penetrate into cell membranes, facilitating improved tissue imaging of cellular internalization, as demonstrated with the luminescence images obtained by multiphoton laser-scanning microscopy. Hence our work opens up a new avenue for exploring effective upconversion nanoparticles for achieving high resolution imaging of plant tissues.Breast cancer (BC) is a heterogeneous disease distinct from major clinical hindrances, and microRNAs (miRNAs) have been accounted to partake in BC progression. Identifying potential miRNAs and their pathological significance in BC could pave the way for precisely targeted treatments. This study exploits transcriptomic BC miRNA, mRNA cohorts, and prognostic significance via an integrative functional approach. check details miRNA transcriptomic cohorts (GSE45666, GSE40267, and GSE19783) were utilized to disseminate differentially expressed miRNAs (DEmiRNAs) and their expression in the clinicopathological variables of BC. miR-182 was identified as a potent candidate, differentially expressed between each BC stage and its adjacent normal samples. The expression of miR-182 was significantly associated with estrogen receptor (ER) (p = 0.052), and closely related to progesterone receptor (PR) (p = 0.061) and human epidermal growth factor receptor 2 (Her2) (p = 0.077). miRNA-mRNA regulatory targets were predicted using six different databases, namely, TargetScan, miRDB, Diana, miRNet, TargetMiner, and miRWalk. Twenty-four promising mRNA regulatory targets were potentially identified for miR-182 and thus highly enriched with cellular metabolic processes, proteoglycans, and focal adhesion pathways in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Subsequently, the F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) gene was recognized as a hub with the highest connectivity score in the protein-protein interaction network. Furthermore, miR-182 and FBXW7 were associated with poor prognostic clinical outcomes in BC patients. Thus, our integrated functional analysis suggests that miR-182 might lead to a new therapeutic target in BC manifestation.Increasing carbon dioxide (CO2) emissions, resulting in climate change, have driven the motivation to achieve the effective and sustainable conversion of CO2 into useful chemicals and fuels. Taking inspiration from biological processes, synthetic iron-nickel-sulfides have been proposed as suitable catalysts for the hydrogenation of CO2. In order to experimentally validate this hypothesis, here we report violarite (Fe,Ni)3S4 as a cheap and economically viable catalyst for the hydrogenation of CO2 into formate under mild, alkaline conditions at 125 °C and 20 bar (CO2 H2 = 1 1). Calcination of violarite at 200 °C resulted in excellent catalytic activity, far superior to that of Fe-only and Ni-only sulfides. We further report first principles simulations of the CO2 conversion on the partially oxidised (001) and (111) surfaces of stoichiometric violarite (FeNi2S4) and polydymite (Ni3S4) to rationalise the experimentally observed trends. We have obtained the thermodynamic and kinetic profiles for the reaction of carbon dioxide (CO2) and water (H2O) on the catalyst surfaces via substitution and dissociation mechanisms. We report that the partially oxidised (111) surface of FeNi2S4 is the best catalyst in the series and that the dissociation mechanism is the most favourable. Our study reveals that the partial oxidation of the FeNi2S4 surface, as well as the synergy of the Fe and Ni ions, are important in the catalytic activity of the material for the effective hydrogenation of CO2 to formate.Cochlear implants (CIs) restore hearing using an array of electrodes implanted in the cochlea to directly stimulate auditory nerve fibers (ANFs). Hearing outcomes with CIs are dependent on the health of the ANFs. In this research, we developed an approach to estimate the health of ANFs using patient-customized, image-based computational models of CI stimulation. Our stimulation models build on a previous model-based solution to estimate the intra-cochlear electric field (EF) created by the CI. Herein, we propose to use the estimated EF to drive ANF models representing 75 nerve bundles along the length of the cochlea. We propose a method to detect the neural health of the ANF models by optimizing neural health parameters to minimize the sum of squared differences between simulated and the physiological measurements available via patients' CIs. The resulting health parameters provide an estimate of the health of ANF bundles. Experiments with 8 subjects show promising model prediction accuracy, with excellent agreement between neural stimulation responses that are clinically measured and those that are predicted by our parameter optimized models. These results suggest our modeling approach may provide an accurate estimation of ANF health for CI users.The cochlear implant (CI) is a neural prosthetic that is the standard-of-care treatment for severe-to-profound hearing loss. CIs consist of an electrode array inserted into the cochlea that electrically stimulates auditory nerve fibers to induce the sensation of hearing. Competing stimuli occur when multiple electrodes stimulate the same neural pathways. This is known to negatively impact hearing outcomes. Previous research has shown that image-processing techniques can be used to analyze the CI position in CT scans to estimate the degree of competition between electrodes based on the CI user's unique anatomy and electrode placement. The resulting data permits an algorithm or expert to select a subset of electrodes to keep active to alleviate competition. Expert selection of electrodes using this data has been shown in clinical studies to lead to significantly improved hearing outcomes for CI users. Currently, we aim to translate these techniques to a system designed for worldwide clinical use, which mandates that the selection of active electrodes be automated by robust algorithms. Previously proposed techniques produce optimal plans with only 48% success rate. In this work, we propose a new graph-based approach. We design a graph with nodes that represent electrodes and edge weights that encode competition between electrode pairs. We then find an optimal path through this graph to determine the active electrode set. Our method produces results judged by an expert to be optimal in over 95% of cases. This technique could facilitate widespread clinical translation of image-guided cochlear implant programming methods.Atypical choroid plexus papilloma is a rare pediatric brain tumor that has distinct clinical and pathologic features. In this case, we highlight the diagnosis and management of this rare disease. The details of case positioning and execution are discussed. The case review is utilized as an overview of histopathologic findings, to discuss clinical features of the disease, and to highlight areas warranting further investigation. In particular, we provide insight into the typical clinical course post-treatment.
Glioblastoma (GBM) is the most common form of brain tumor and has a uniformly poor prognosis. Development of prognostic biomarkers in easily accessible serum samples have the potential to improve the outcomes of patients with GBM through personalized therapy planning.
In this study pre-treatment serum samples from 30 patients newly diagnosed with GBM were evaluated using a 40-protein multiplex ELISA platform. Analysis of potentially relevant gene targets using The Cancer Genome Atlas database was done using the Glioblastoma Bio Discovery Portal (GBM-BioDP). A ten-biomarker subgroup of clinically relevant molecules was selected using a functional grouping analysis of the 40 plex genes with two genes selected from each group on the basis of degree of variance, lack of co-linearity with other biomarkers and clinical interest. A Multivariate Cox proportional hazard approach was used to analyze the relationship between overall survival (OS), gene expression, and resection status as covariates.
Thirty of 40 ote that proteomic approaches to the development of prognostic assays for treatment of GBM may hold potential clinical value.
These findings demonstrate that proteomic approaches to the development of prognostic assays for treatment of GBM may hold potential clinical value.Genetic counselors are trained to deliver complicated genomic test results to parents of pediatric patients. However, there is limited knowledge on how parents perceive this information and what they understand about the results. This research aims to qualitatively explore parents' experiences receiving genomic test results for their children. As part of formative research for the NYCKidSeq Study, we recruited a purposive sample of parents of 22 children stratified by child race/ethnicity and test result classification (positive, uncertain, or negative) and conducted in-depth interviews using a semi-structured guide. Analysis was conducted using grounded theory's constant comparative method across cases and themes. Parents described different elements of understanding genetics knowledge; significance and meaning of positive, uncertain, or negative results; and implications for the health of their child and family. Parents reported challenges understanding technical details and significance of their child's results but gladly allowed their providers to be custodians of this information. However, of the different elements of understanding described, parents cared most deeply about being able to understand implications for their child's and family's health. These findings suggest that a counseling approach that primarily addresses parents' desire to understand how to best care for their child and family may be more appropriate than an information-heavy approach focused on technical details. Further research is warranted to confirm these findings in larger parent cohorts and to explore ways genetic counseling can support parents' preferences without sacrificing important components of parent understanding and overall satisfaction with their experiences with genomic medicine.Venetoclax with azacitidine (ven/aza) has emerged as a promising regimen for acute myeloid leukemia (AML), with a high percentage of clinical remissions in newly diagnosed patients. However, approximately 30% of newly diagnosed and the majority of relapsed patients do not achieve remission with ven/aza. We previously reported that ven/aza efficacy is based on eradication of AML stem cells through a mechanism involving inhibition of amino acid metabolism, a process which is required in primitive AML cells to drive oxidative phosphorylation. Herein we demonstrate that resistance to ven/aza occurs via up-regulation of fatty acid oxidation (FAO), which occurs due to RAS pathway mutations, or as a compensatory adaptation in relapsed disease. Utilization of FAO obviates the need for amino acid metabolism, thereby rendering ven/aza ineffective. Pharmacological inhibition of FAO restores sensitivity to ven/aza in drug resistant AML cells. We propose inhibition of FAO as a therapeutic strategy to address ven/aza resistance.