87,556 research outputs found

    Intramolecular (4 + 3) cycloadditions of oxidopyridinium ions : towards daphnicyclidin A

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    [EMBARGOED UNTIL 5/1/2024] N-alkylation of alkyl 5-hydroxynicotinates with electrophiles containing diene functionality produces salts , which can undergo intramolecular (4 + 3) cycloaddition reactions when heated in the presence of a base. Initially, a three-carbon tether was used to connect the pyridinium ion and the diene. However, synthesizing related compounds with a two-carbon tether proved to be much more challenging. To overcome this obstacle, a dimethylenecyclopentane was successfully synthesized, and a sulfur dioxide protection was introduced. Using these compounds, the researchers were able to successfully achieve the cycloaddition reaction, leading directly to the ABC tricyclic ring system, as well as the ABCE tetracyclic ring system found in the alkaloid daphnicyclidin A.Includes bibliographical references

    Research on automatic grinding platform for rare earth ingot casting

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    Aiming at the problems of low grinding efficiency and difficulty in ensuring grinding uniformity of rare earth metal ingots, a rare earth metal ingot grinding system was designed. Based on Creo software and ANSYS/Workbench software, the kinematics analysis, modal analysis and transient dynamics analysis were carried out on the walking mechanism and flipping mechanism of automatic displacement platform of grinding system. The results show that the rare earth metal ingot grinding system has good stability and is beneficial to improving the grinding quality

    DataSheet_1_Development of a prognostic Neutrophil Extracellular Traps related lncRNA signature for soft tissue sarcoma using machine learning.pdf

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    BackgroundSoft tissue sarcoma (STS) is a highly heterogeneous musculoskeletal tumor with a significant impact on human health due to its high incidence and malignancy. Long non-coding RNA (lncRNA) and Neutrophil Extracellular Traps (NETs) have crucial roles in tumors. Herein, we aimed to develop a novel NETsLnc-related signature using machine learning algorithms for clinical decision-making in STS.MethodsWe applied 96 combined frameworks based on 10 different machine learning algorithms to develop a consensus signature for prognosis and therapy response prediction. Clinical characteristics, univariate and multivariate analysis, and receiver operating characteristic curve (ROC) analysis were used to evaluate the predictive performance of our models. Additionally, we explored the biological behavior, genomic patterns, and immune landscape of distinct NETsLnc groups. For patients with different NETsLnc scores, we provided information on immunotherapy responses, chemotherapy, and potential therapeutic agents to enhance the precision medicine of STS. Finally, the gene expression was validated through real-time quantitative PCR (RT-qPCR).ResultsUsing the weighted gene co-expression network analysis (WGCNA) algorithm, we identified NETsLncs. Subsequently, we constructed a prognostic NETsLnc signature with the highest mean c-index by combining machine learning algorithms. The NETsLnc-related features showed excellent and stable performance for survival prediction in STS. Patients in the low NETsLnc group, associated with improved prognosis, exhibited enhanced immune activity, immune infiltration, and tended toward an immunothermal phenotype with a potential immunotherapy response. Conversely, patients with a high NETsLnc score showed more frequent genomic alterations and demonstrated a better response to vincristine treatment. Furthermore, RT-qPCR confirmed abnormal expression of several signature lncRNAs in STS.ConclusionIn conclusion, the NETsLnc signature shows promise as a powerful approach for predicting the prognosis of STS. which not only deepens our understanding of STS but also opens avenues for more targeted and effective treatment strategies.</p

    Table4_TNIK regulation of interferon signaling and endothelial cell response to virus infection.docx

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    BackgroundTraf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored.MethodsLeveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs.ResultsExamination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log (p-value) >11], downregulation of IFN-related genes, and inhibition of Hypercytokinemia/Hyperchemokinemia [-log (p-value) >8]. The validation process encompassed qRT-PCR to evaluate mRNA expression of crucial IFN-related genes, immunoblotting to gauge STAT1 and STAT2 protein levels, and ELISA for the quantification of IFN and cytokine secretion in siTNIK-depleted ECs. These assessments consistently revealed substantial reductions upon TNIK depletion. When transducing HUVECs with replication incompetent E1-E4 deleted adenovirus expressing green fluorescent protein (Ad-GFP), it was demonstrated that TNIK depletion did not affect the uptake of Ad-GFP. Nonetheless, TNIK depletion induced cytopathic effects (CPE) in ECs transduced with wild-type human adenovirus serotype 5 (Ad-WT).SummaryOur findings suggest that TNIK plays a crucial role in regulating the EC response to virus infections through modulation of the IFN pathway.</p

    Seasonal variations of metals and metalloids in atmospheric particulate matter (PM2.5) in the urban megacity Hanoi

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    International audienceFine particulate matter (PM2.5) in the atmosphere is of particular concern due to its adverse effects on human health and its impact on global warming. southeast Asia is a hot spot for fossil fuel combustion with recurrent release of large plumes spreading over the ocean and neighbouring countries. Due to the complex mixture of PM2.5, the atmospheric sources contribution related to local and regional emissions in Hanoi (northern Vietnam) is still ill-constrained. Here, we present a year-round study (November 2019 to December 2020) with measurements of 18 metals and metalloids (MM) and lead isotopes in the PM2.5 fraction to quantify weather-related atmospheric inputs and to assess risk to human health. Anthropogenic inputs from fossil fuel combustion accounted for about 80% in PM2.5. We found high PM2.5-bound MM concentrations often exceeding national and global standards with a low risk of chronic inhalation and carcinogenicity, mainly attributable to Cr. During winter monsoon (northeastern winds), stable weather conditions led to the enrichment of long-range air mass transport of local particulate emissions. During the summer monsoon (southeastern winds), warm and moist winds reduced coal contribution in PM2.5. Our study highlights the need for a strict implementation of policies to control hazardous MM emissions by reducing fossil fuel combustion. On the one hand, reducing coal-related activities could reduce Cr emissions and therefore improve the risks to human health. On the other hand, public policies should encourage conversion to green transport in order to reduce petrol combustion and thus limit global warming

    Descriptive statistics.

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    As the world’s largest emitter of carbon, China has implemented a series of environmental regulatory policies to reduce emissions. However, most of these environmental regulations have been at the expense of increased corporate environmental costs. Therefore, research on how to efficiently control these costs is of significant practical importance. This paper uses the China’s carbon trading policy (CTP) implemented in 2013 as a quasi-natural experiment, utilizing data from Chinese listed manufacturing firms between 2008 and 2020. Employing a difference-in-differences (DID) model, the study investigates the impact of market-incentive environmental regulatory policies (ERP) on environmental costs. The findings reveal that CTP significantly reduced the environmental costs of firms, confirming the positive and vital role market-incentive ERP can play in environmental protection and cost control. These conclusions remain robust after a series of stability tests. Mechanism analysis suggests that the cost reductions brought by market-incentive ERP are primarily achieved through increasing green innovation. Heterogeneity analysis shows that non-state-owned enterprises (non-SOEs), key polluting firms, firms with lower financial constraints, and firms with lower total production efficiency benefit more from market-incentive environmental regulatory policies. This study provides new empirical evidence for government policy-making aimed at achieving long-term sustainable development.</div

    The value of the accelerated approval pathway: Real-world outcomes associated with reducing the time between innovations - supplementary material

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    Supplementary table 1. Patient selection and attrition.Supplementary table 2. Patient characteristics.Supplementary table 3. Proportion of patients surviving to the AA date in real-world database and population level.Supplementary figure </p

    T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID

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    BackgroundAs about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.MethodTo this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later.ResultsNone of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016).ConclusionsOur observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID

    Extracting the speed of sound in the strongly interacting matter created in ultrarelativistic lead-lead collisions at the LHC