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Nucleic acid aptamers are small fragments of DNA or RNA molecules binding specifically to targets, which can be obtained through in vitro screening via systematic evolution of ligands by exponential enrichment (SELEX). Lactate dehydrogenase (LDH) is an important tumor marker, whose level in patients is of great significance for diagnosis of many diseases. Here, we report the identification of LDH aptamers by 9 rounds of screening from a length-mixed single-stranded DNA library using the SELEX technology. After the 3rd and 7th rounds of aptamer screening, affinity was significantly improved, and fluorescence quantitative analysis showed stronger affinity for the aptamers selected from the 7th to 9th rounds of screening. After high-throughput sequencing, motif analysis, and secondary structure prediction, we finally chose and further investigated 15 candidate LDH aptamer sequences with obvious differences in secondary structure in the 7th to 9th rounds of screening. Among them, LDH7-1, LDH7-9, LDH8-2, and LDH9-1 were shown to bind to LDH protein with high affinity and specificity with Kd less then 25 nM. This study provides new ideas for rapid detection of LDH protein content and enzyme activity, thus contributing to the development of rapid medical detection.Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a pandemic affecting many countries and millions of people. Physicians have encountered some rare and challenging cases related to SARS-CoV-2, a novel virus with still many unknowns. In order to share our experience of a such clinical picture, we present here a child with SARS-CoV-2-induced macrophage activation syndrome in the setting of juvenile idiopathic arthritis.The pathology of primary ciliary dyskinesia (PCD) is predominantly attributed to impairment of motile cilia. However, PCD patients also have perplexing functional defects in myeloid cells, which lack motile cilia. Here, we show that coiled-coil domain-containing protein 103 (CCDC103), one of the genes that, when mutated, is known to cause PCD, is required for the proliferation and directed migration of myeloid cells. CCDC103 is expressed in human myeloid cells, where it colocalizes with cytoplasmic microtubules. Zebrafish ccdc103/schmalhans (smh) mutants have macrophages and neutrophils with reduced proliferation, abnormally rounded cell morphology and an inability to migrate efficiently to the site of sterile wounds, all of which are consistent with a loss of cytoplasmic microtubule stability. Furthermore, we demonstrate that direct interactions between CCDC103 and sperm associated antigen 6 (SPAG6), which also promotes microtubule stability, are abrogated by CCDC103 mutations from PCD patients, and that spag6 zebrafish mutants recapitulate the myeloid defects observed in smh mutants. In summary, we have illuminated a mechanism, independent of motile cilia, to explain functional defects in myeloid cells from PCD patients. This article has an associated First Person interview with the first author of the paper.
Joint profiling of single-cell transcriptomics and epigenomics data enables us to characterize cell states and transcriptomics regulatory programs related to cellular heterogeneity. However, the highly different features on sparsity, heterogeneity, and dimensionality between multi-omics data have severely hindered its integrative analysis.
We proposed deep cross-omics cycle attention (DCCA) model, a computational tool for joint analysis of single-cell multi-omics data, by combining variational autoencoders (VAEs) and attention-transfer. Specifically, we show that DCCA can leverage one omics data to fine-tune the network trained for another omics data, given a dataset of parallel multi-omics data within the same cell. Studies on both simulated and real datasets from various platforms, DCCA demonstrates its superior capability (i) dissecting cellular heterogeneity; (ii) denoising and aggregating data; and (iii) constructing the link between multi-omics data, which is used to infer new transcriptional regulatory relations. In our applications, DCCA was demonstrated to have a superior power to generate missing stages or omics in a biologically meaningful manner, which provides a new way to analyze and also understand complicated biological processes.
DCCA source code is available at https//github.com/cmzuo11/DCCA, and has been deposited in archived format at https//doi.org/10.5281/zenodo.4762065.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
Gamification is increasingly being used to promote healthy behaviors. However, it has not been well tested among patients with chronic conditions and over longer durations.
To test the effectiveness of behaviorally designed gamification interventions to enhance support, collaboration, or competition to promote physical activity and weight loss among adults with uncontrolled type 2 diabetes.
A 4-arm randomized clinical trial with a 1-year intervention was conducted from January 23, 2017, to January 27, 2020, with remotely monitored intervention. Analyses were conducted between February 10 and October 6, 2020. Participants included 361 adults with type 2 diabetes with hemoglobin A1c levels greater than or equal to 8% and body mass index greater than or equal to 25.
All participants received a wearable device, smart weight scale, and laboratory testing. Participants in the control group received feedback from their devices but no other interventions. Participants in the gamification arms conducted goal sicalTrials.gov Identifier NCT02961192.
Unreported clinical trial results represent a violation of human rights. Oncology trials account for nearly 30% of interventional biopharmaceutical clinical studies registered on ClinicalTrials.gov and are the most numerous among all disciplines.
To analyze the reporting of results among all interventional oncology trials registered on ClinicalTrials.gov from 2007 through 2017.
This cohort study analyzed all clinical studies registered between June 1, 2007, and May 8, 2017, on ClinicalTrials.gov, the largest public clinical trial registry in the world. Trials with a recruitment status of completed or terminated and a primary completion date of on or before September 30, 2017, were selected. Data were analyzed between February 20, 2021, and February 26, 2021.
The main outcome was the percentage of trials that reported results either on ClinicalTrials.gov or in journal publications within 24 months of the primary completion date. Selleckchem BMS309403 Journal publication was ascertained by searching ClinicalTrials.gov for a link to the publication, PubMed using national clinical trial number, and Embase using national clinical trial number and filters.
Homepage: https://www.selleckchem.com/products/bms309403.html
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