5,881 research outputs found
Characterization and identification of in vitro metabolites of (-)-epicatechin using ultra-high performance liquid chromatography-mass spectrometry
Purpose: To characterize and identify metabolites of (-)-epicatechin in microsomal fraction of rat hepatocytes (MFRHs). Methods: A single incubation of (-)-epicatechin (1 mL, 50 µg/mL) in MFRH (0.5 mg/mL) was used for the generation of metabolites. Thereafter, the sample was subjected to protein precipitation prior to analysis with ultra-high performance liquid chromatography coupled to linear ion-trap orbitrap mass spectrometry (UHPLC-LTQ-Orbitap MS). Results: Nine metabolites of (-)-epicatechin were characterized on the basis of high resolution mass measurement, MS spectra and literature data. Based on their structures, the major metabolic routes of (-)-epicatechin in MFRHs were identified as hydroxylation, dihydroxylation and glycosylation. Conclusion: This is the first report on metabolites of (-)-epicatechin in MFRHs, and it is helpful in gaining deeper insight into the metabolism of (-)-epicatechin in vivo. The results will also provide guidance in research on the pharmacokinetics of new drugs. Keywords: (-)-Epicatechin, Metabolites, Hydroxylation, Dihydroxylation, Glycosylation, Rat liver microsomes, Pharmacokinetic studie
Life fingerprints of nuclear reactions in the body of animals
Nuclear reactions are a very important natural phenomenon in the universe. On the earth, cosmic rays constantly cause nuclear reactions. High energy beams created by medical devices also induce nuclear reactions in the human body. The biological role of these nuclear reactions is unknown. Here we show that the in vivo biological systems are exquisite and sophisticated by nature in influence on nuclear reactions and in resistance to radical damage in the body of live animals. In this study, photonuclear reactions in the body of live or dead animals were induced with 50-MeV irradiation. Tissue nuclear reactions were detected by positron emission tomography (PET) imaging of the induced beta+ activity. We found the unique tissue "fingerprints" of beta+ (the tremendous difference in beta+ activities and tissue distribution patterns among the individuals) are imprinted in all live animals. Within any individual, the tissue "fingerprints" of 15O and 11C are also very different. When the animal dies, the tissue "fingerprints" are lost. The biochemical, rather than physical, mechanisms could play a critical role in the phenomenon of tissue "fingerprints". Radiolytic radical attack caused millions-fold increases in 15O and 11C activities via different biochemical mechanisms, i.e. radical-mediated hydroxylation and peroxidation respectively, and more importantly the bio-molecular functions (such as the chemical reactivity and the solvent accessibility to radicals). In practice biologically for example, radical attack can therefore be imaged in vivo in live animals and humans using PET for life science research, disease prevention, and personalized radiation therapy based on an individual's bio-molecular response to ionizing radiation
DGI: Easy and Efficient Inference for GNNs
While many systems have been developed to train Graph Neural Networks (GNNs),
efficient model inference and evaluation remain to be addressed. For instance,
using the widely adopted node-wise approach, model evaluation can account for
up to 94% of the time in the end-to-end training process due to neighbor
explosion, which means that a node accesses its multi-hop neighbors. On the
other hand, layer-wise inference avoids the neighbor explosion problem by
conducting inference layer by layer such that the nodes only need their one-hop
neighbors in each layer. However, implementing layer-wise inference requires
substantial engineering efforts because users need to manually decompose a GNN
model into layers for computation and split workload into batches to fit into
device memory. In this paper, we develop Deep Graph Inference (DGI) -- a system
for easy and efficient GNN model inference, which automatically translates the
training code of a GNN model for layer-wise execution. DGI is general for
various GNN models and different kinds of inference requests, and supports
out-of-core execution on large graphs that cannot fit in CPU memory.
Experimental results show that DGI consistently outperforms layer-wise
inference across different datasets and hardware settings, and the speedup can
be over 1,000x.Comment: 10 pages, 10 figure
Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia
To investigate the effect of pentoxifylline (PTX) on spermatogenesis dysfunction induced by intermittent hypobaric hypoxia (IHH) and unveil the underlying mechanism, experimental animals were assigned to Control, IHH+Vehicle, and IHH+PTX groups and exposed to 4 cycles of 96 h of hypobaric hypoxia followed by 96 h of normobaric normoxia for 32 days. PTX was administered for 32 days. Blood and tissue samples were collected 7 days thereafter. Serum malondialdehyde levels were used to assess lipid peroxidation; ferric-reducing antioxidant power (FRAP), superoxide dismutase, and catalase and glutathione peroxidase enzyme activities were assessed to determine antioxidant capacity in various samples. Testis histopathology was assessed after hematoxylin-eosin staining by Johnsen’s testicular scoring system. Meanwhile, testosterone synthase and vimentin amounts were assessed by immunohistochemistry. Sperm count, motility, and density were assessed to determine epididymal sperm quality. IHH treatment induced significant pathological changes in testicular tissue and enhanced serum lipid peroxide levels, while reducing serum FRAP, antioxidant enzyme activities, and testosterone synthase expression. Moreover, IHH impaired epididymal sperm quality and vimentin structure in Sertoli cells. Oral administration of PTX improved the pathological changes in the testis. IHH may impair spermatogenesis function of testicular tissues by inducing oxidative stress, but this impairment could be attenuated by administration of PTX
Atomic resolution imaging of the two-component Dirac-Landau levels in a gapped graphene monolayer
The wavefunction of massless Dirac fermions is a two-component spinor. In
graphene, a one-atom-thick film showing two-dimensional Dirac-like electronic
excitations, the two-component representation reflects the amplitude of the
electron wavefunction on the A and B sublattices. This unique property provides
unprecedented opportunities to image the two components of massless Dirac
fermions spatially. Here we report atomic resolution imaging of the
two-component Dirac-Landau levels in a gapped graphene monolayer by scanning
tunnelling microscopy and spectroscopy. A gap of about 20 meV, driven by
inversion symmetry breaking by the substrate potential, is observed in the
graphene on both SiC and graphite substrates. Such a gap splits the n = 0
Landau level (LL) into two levels, 0+ and 0-. We demonstrate that the amplitude
of the wavefunction of the 0- LL is mainly at the A sites and that of the 0+ LL
is mainly at the B sites of graphene, characterizing the internal structure of
the spinor of the n = 0 LL. This provides direct evidence of the two-component
nature of massless Dirac fermions.Comment: 4 Figures in main text and 4 Figures in S
Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury
Acute kidney injury (AKI) is a syndrome of abrupt loss of renal functions. The underlying pathological mechanisms of AKI remain largely unknown. BCL2-interacting protein 3 (BNIP3) has dual functions of regulating cell death and mitophagy, but its pathophysiological role in AKI remains unclear. Here, we demonstrated an increase of BNIP3 expression in cultured renal proximal tubular epithelial cells following oxygen-glucose deprivation-reperfusion (OGD-R) and in renal tubules after renal ischemia-reperfusion (IR)-induced injury in mice. Functionally, silencing Bnip3 by specific short hairpin RNAs in cultured renal tubular cells reduced OGD-R-induced mitophagy, and potentiated OGD-R-induced cell death. In vivo, Bnip3 knockout worsened renal IR injury, as manifested by more severe renal dysfunction and tissue injury. We further showed that Bnip3 knockout reduced mitophagy, which resulted in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and enhanced cell death and inflammatory response in kidneys following renal IR. Taken together, these findings suggest that BNIP3-mediated mitophagy has a critical role in mitochondrial quality control and tubular cell survival during AKI
Direct generation of time-energy-entangled W triphotons in atomic vapor
Sources of entangled multiphotons are not only essential for fundamental
tests of quantum foundations, but are also the cornerstone of a variety of
optical quantum technologies today. Over past three decades, tremendous efforts
have been devoted to creating multiphoton entanglement by multiplexing existing
biphoton sources with linear optics and postselections. Different from all
previous protocols, here we report, for the first time, the observation of
continuous-mode time-energy-entangled W-class triphotons with an unprecedented
generation rate directly through the process of spontaneous six-wave mixing
(SSWM) in a four-level triple-Lambda atomic vapor cell. Facilitated by
electromagnetically induced transparency and coherence control, our SSWM scheme
enables versatile narrowband triphoton generation with many intriguing
properties including long temporal coherence and controllable waveforms, ideal
for implementing long-distance quantum communications, networking, and
information processing by interfacing photons and atoms. Most importantly, our
work paves a way for the development of a reliable and efficient genuine
triphoton source, thus making the research on multiphoton entanglement within
easy reach.Comment: welcome the comment
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