3,721 research outputs found
Human Circulating MicroRNA-1 and MicroRNA-126 as Potential Novel Indicators for Acute Myocardial Infarction
Circulating miRNAs have been shown as promising biomarkers for various pathologic conditions. The aim of this study was to clarify that circulating miR-1 and miR-126 in human plasma might be useful as biomarkers in acute myocardial infarction (AMI). In our study, after pre-test, two candidate miRNAs were detected by using real-time RT-PCR. Cardiac troponin I (cTnI) concentrations were measured by ELISA assay in plasma from patients with AMI (n=17) and healthy subjects (n=25), simultaneously. Increased miR-1 and decreased miR-126 in plasma from patients with AMI after the onset of symptoms compared with healthy subjects were found. A remarkable finding in this study is that miR-1, miR-126 and cTnI expression levels exhibited the same trend. Our results suggest that the plasma concentrations of miR-1 and miR-126 may be useful indicators for AMI
Trimetazidine Attenuates Cardiac Dysfunction in Endotoxemia and Sepsis by Promoting Neutrophil Migration
Aims: Cardiac dysfunction can be a fatal complication during severe sepsis. The migration of neutrophils is significantly impaired during severe sepsis. We sought to determine the role of trimetazidine (TMZ) in regulation of neutrophil migration to the heart in a mouse model of sepsis and endotoxemia, and to identify the mechanism whereby TMZ confers a survival advantage.Methods and Results: C57/BL6 mice were (1) injected with LPS followed by 24-h TMZ administration, or (2) treated with TMZ (20 mg/kg/day) for 1 week post cecal ligation and puncture (CLP) operation. Echocardiography and Millar system detection showed that TMZ alleviated cardiac dysfunction and histological staining showed the failure of neutrophils migration to heart in both LPS- and CLP-induced mice. Bone marrow transplantation revealed that TMZ-pretreated bone marrow cells improved LPS- and CLP-induced myocardial dysfunction and enhanced neutrophil recruitment in heart. In CXCL2-mediated chemotaxis assays, TMZ increased neutrophils migration via AMPK/Nrf2-dependent up-regulation of CXCR2 and inhibition of GRK2. Furthermore, using luciferase reporter gene and chromatin immunoprecipitation assays, we found that TMZ promoted the binding of the Nrf2 and CXCR2 promoter regions directly. Application of CXCR2 inhibitor completely reversed the protective effects of TMZ in vivo. Co-culture of neutrophils and cardiomyocytes further validated that TMZ decreased LPS-induced cardiomyocyte pyroptosis by targeting neutrophils.Conclusion: Our findings suggested TMZ as a potential therapeutic agent for septic or endotoxemia associated cardiac dysfunction in mice.STUDY HIGHLIGHTSÂ What is the current knowledge on the topic?Migration of neutrophils is significantly impaired during severe sepsis, but the underlying mechanisms remain unknown.What question did this study address?The effects of TMZ on cardiac dysfunction via neutrophils migration.What this study adds to our knowledgeTMZ attenuated LPS-induced cardiomyocyte pyroptosis and cardiac dysfunction by promoting neutrophils recruitment to the heart tissues via CXCR2.How this might change clinical pharmacology or translational scienceOur findings suggested TMZ as a potential therapeutic agent for septic cardiac dysfunction
Altaicalarins A−D, Cytotoxic Bisabolane Sesquiterpenes from Ligularia altaica
Four new bisabolane sesquiterpenes, altaicalarins A–D (1–4) and three known analogues (5–7) were isolated from the roots and rhizomes of Ligularia altaica. The structures were elucidated by spectroscopic methods including 2D NMR techniques, and the structure of 1 was confirmed by single-crystal X-ray diffraction. The isolated compounds were also evaluated for cytotoxic activity against human lung carcinoma (A-549), human breast adenocarcinoma (MCF-7), epidermoid carcinoma of the nasopharynx (KB), and vincristine-resistant nasopharyngeal (KBVIN) cell lines, and 1 was found to show significant cytotoxicity with EC50 values of 3.4, 0.8, 1.0, and 0.9 µg/mL, respectively
Deja Vu: Contextual Sparsity for Efficient LLMs at Inference Time
Large language models (LLMs) with hundreds of billions of parameters have
sparked a new wave of exciting AI applications. However, they are
computationally expensive at inference time. Sparsity is a natural approach to
reduce this cost, but existing methods either require costly retraining, have
to forgo LLM's in-context learning ability, or do not yield wall-clock time
speedup on modern hardware. We hypothesize that contextual sparsity, which are
small, input-dependent sets of attention heads and MLP parameters that yield
approximately the same output as the dense model for a given input, can address
these issues. We show that contextual sparsity exists, that it can be
accurately predicted, and that we can exploit it to speed up LLM inference in
wall-clock time without compromising LLM's quality or in-context learning
ability. Based on these insights, we propose DejaVu, a system that uses a
low-cost algorithm to predict contextual sparsity on the fly given inputs to
each layer, along with an asynchronous and hardware-aware implementation that
speeds up LLM inference. We validate that DejaVu can reduce the inference
latency of OPT-175B by over 2X compared to the state-of-the-art
FasterTransformer, and over 6X compared to the widely used Hugging Face
implementation, without compromising model quality. The code is available at
https://github.com/FMInference/DejaVu
Differential Effects Of Conifer And Broadleaf Litter Inputs On Soil Organic Carbon Chemical Composition Through Altered Soil Microbial Community Composition
A strategic selection of tree species will shift the type and quality of litter input, and subsequently magnitude and composition of the soil organic carbon (SOC) through soil microbial community. We conducted a manipulative experiment in randomized block design with leaf litter inputs of four native subtropical tree species in a Pinus massoniana plantation in southern China and found that the chemical composition of SOC did not differ significantly among treatments until after 28 months of the experiment. Contrasting leaf litter inputs had significant impacts on the amounts of total microbial, Gram-positive bacterial, and actinomycic PLFAs, but not on the amounts of total bacterial, Gramnegative bacterial, and fungal PLFAs. There were significant differences in alkyl/O-alkyl C in soils among the leaf litter input treatments, but no apparent differences in the proportions of chemical compositions (alkyl, O-alkyl, aromatic, and carbonyl C) in SOC. Soil alkyl/O-alkyl C was significantly related to the amounts of total microbial, and Gram-positive bacterial PLFAs, but not to the chemical compositions of leaf litter. Our findings suggest that changes in forest leaf litter inputs could result in changes in chemical stability of SOC through the altered microbial community composition
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