The Role of 7,8-Dihydroxyflavone in Preventing Dendrite Degeneration in Cortex After Moderate Traumatic Brain Injury

Our previous research showed that traumatic brain injury (TBI) induced by controlled cortical impact (CCI) not only causes massive cell death, but also results in extensive dendrite degeneration in those spared neurons in the cortex. Cell death and dendrite degeneration in the cortex may contribute to persistent cognitive, sensory, and motor dysfunction. There is still no approach available to prevent cells from death and dendrites from degeneration following TBI. When we treated the animals with a small molecule, 7,8-dihydroxyflavone (DHF) that mimics the function of brain-derived neurotrophic factor (BDNF) through provoking TrkB activation reduced dendrite swellings in the cortex. DHF treatment also prevented dendritic spine loss after TBI. Functional analysis showed that DHF improved rotarod performance on the third day after surgery. These results suggest that although DHF treatment did not significantly reduced neuron death, it prevented dendrites from degenerating and protected dendritic spines against TBI insult. Consequently, DHF can partially improve the behavior outcomes after TBI

An Efficient Universal Noise Removal Algorithm Combining Spatial Gradient and Impulse Statistic

We propose a novel universal noise removal algorithm by combining spatial gradient and a new impulse statistic into the trilateral filter. By introducing a reference image, an impulse statistic is proposed, which is called directional absolute relative differences (DARD) statistic. Operation was carried out in two stages: getting reference image and image denoising. For denoising, we introduce the spatial gradient into the Gaussian filtering framework for Gaussian noise removal and integrate our DARD statistic for impulse noise removal, and finally we combine them together to create a new trilateral filter for mixed noise removal. Simulation results show that our noise detector has a high classification rate, especially for salt-and-pepper noise. And the proposed approach achieves great results both in terms of quantitative measures of signal restoration and qualitative judgments of image quality. In addition, the computational complexity of the proposed method is less than that of many other mixed noise filters

Medical treatment and long-term outcome of chronic atrial fibrillation in the aged with chest distress: a retrospective analysis versus sinus rhythm

Although “chest distress” is the most frequent complication in the aged with chronic atrial frbrillation (AF) in clinical practice, there are few data on the association between chronic AF and coronary artery disease (CAD) in the aged in terms of medical treatment and long-term outcome. We assessed coronary artery lesions in such patients and evaluated the efficacy of medical treatment in long-term follow-ups. Of 315 elderly patients (mean age: 77.39 ± 6.33 years) who had undergone coronary angiography for chest distress, 297 exhibited sinus rhythm (SR), whereas 18 patients exhibited chronic AF. Patients with AF were followed for 4.22 ± 2.21 years. Average diastolic blood pressure (DBP) of AF patients was observed to be markedly less than that of patients with SR (57.33 ± 6.87 mmHg vs 71.08 ± 10.54 mmHg, t-test: P < 0.01). Compared with SR patients, severe stenosis of the coronary artery in AF patients was reduced (73.06% vs 44.44%, Chi-square test: P < 0.01). AF patients with chest distress had high CHADS2 score (3.72 ± 1.27), but only 33.3% patients received oral anticoagulants, and such patients had a significantly lower rate of revascularization (21.43% vs 55.63%, Chi-square test: P < 0.01), and higher rate of all-cause death (22.22% vs 4.38%, Chi-square test: P < 0.01) and thromboembolism (16.67% vs 1.68%, Chi-square test: P < 0.01) in the long-term follow-ups compared with SR patients. Chest distress in the aged with AF was related to insufficient coronary blood supply that was primarily due to a reduced DBP rather than to occult CAD. Adequate and safe medical therapy was difficult to achieve in these patients. Such patients typically have a poor prognosis, and optimal therapeutic strategies to treat them are urgently needed

Protective effect of Macleaya cordata isoquinoline alkaloids on lipopolysaccharide-induced liver injury in broilers

Objective This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. Methods Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. Results Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Conclusion Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers

Concept for a Future Super Proton-Proton Collider

Following the discovery of the Higgs boson at LHC, new large colliders are being studied by the international high-energy community to explore Higgs physics in detail and new physics beyond the Standard Model. In China, a two-stage circular collider project CEPC-SPPC is proposed, with the first stage CEPC (Circular Electron Positron Collier, a so-called Higgs factory) focused on Higgs physics, and the second stage SPPC (Super Proton-Proton Collider) focused on new physics beyond the Standard Model. This paper discusses this second stage.Comment: 34 pages, 8 figures, 5 table

STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells

Production of TGF-β by T cells is key to various aspects of immune homeostasis, with defects in this process causing or aggravating immune-mediated disorders. The molecular mechanisms that lead to TGF-β generation by T cells remain largely unknown. To address this issue, we take advantage of the fact that intestinal helminths stimulate Th2 cells besides triggering TGF-β generation by T lymphocytes and regulate immune-mediated disorders. We show that the Th2 cell-inducing transcription factor STAT6 is necessary and sufficient for the expression of TGF-β propeptide in T cells. STAT6 is also necessary for several helminth-triggered events in mice, such as TGF-β-dependent suppression of alloreactive inflammation in graft-versus-host disease. Besides STAT6, helminth-induced secretion of active TGF-β requires cleavage of propeptide by the endopeptidase furin. Thus, for the immune regulatory pathway necessary for TGF-β production by T cells, our results support a two-step model, composed of STAT6 and furin

SimRank*: effective and scalable pairwise similarity search based on graph topology

Given a graph, how can we quantify similarity between two nodes in an effective and scalable way? SimRank is an attractive measure of pairwise similarity based on graph topologies. Its underpinning philosophy that “two nodes are similar if they are pointed to (have incoming edges) from similar nodes” can be regarded as an aggregation of similarities based on incoming paths. Despite its popularity in various applications (e.g., web search and social networks), SimRank has an undesirable trait, i.e., “zero-similarity”: it accommodates only the paths of equal length from a common “center” node, whereas a large portion of other paths are fully ignored. In this paper, we propose an effective and scalable similarity model, SimRank*, to remedy this problem. (1) We first provide a sufficient and necessary condition of the “zero-similarity” problem that exists in Jeh and Widom’s SimRank model, Li et al. ’s SimRank model, Random Walk with Restart (RWR), and ASCOS++. (2) We next present our treatment, SimRank*, which can resolve this issue while inheriting the merit of the simple SimRank philosophy. (3) We reduce the series form of SimRank* to a closed form, which looks simpler than SimRank but which enriches semantics without suffering from increased computational overhead. This leads to an iterative form of SimRank*, which requires O(Knm) time and O(n2) memory for computing all (n2) pairs of similarities on a graph of n nodes and m edges for K iterations. (4) To improve the computational time of SimRank* further, we leverage a novel clustering strategy via edge concentration. Due to its NP-hardness, we devise an efficient heuristic to speed up all-pairs SimRank* computation to O(Knm~) time, where m~ is generally much smaller than m. (5) To scale SimRank* on billion-edge graphs, we propose two memory-efficient single-source algorithms, i.e., ss-gSR* for geometric SimRank*, and ss-eSR* for exponential SimRank*, which can retrieve similarities between all n nodes and a given query on an as-needed basis. This significantly reduces the O(n2) memory of all-pairs search to either O(Kn+m~) for geometric SimRank*, or O(n+m~) for exponential SimRank*, without any loss of accuracy, where m~≪n2 . (6) We also compare SimRank* with another remedy of SimRank that adds self-loops on each node and demonstrate that SimRank* is more effective. (7) Using real and synthetic datasets, we empirically verify the richer semantics of SimRank*, and validate its high computational efficiency and scalability on large graphs with billions of edges

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

ZEB2 Mediates Multiple Pathways Regulating Cell Proliferation, Migration, Invasion, and Apoptosis in Glioma

BACKGROUND: The aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2) in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Expression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot. RESULTS: The expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (P<0.001). In addition, high levels of ZEB2 protein were positively correlated with pathology grade classification (P = 0.024) of glioma patients. Knockdown of ZEB2 by siRNA suppressed cell proliferation, migration and invasion, as well as induced cell apoptosis in glioma cells. Furthermore, ZEB2 downregulation was accompanied by decreased expression of CDK4/6, Cyclin D1, Cyclin E, E2F1, and c-myc, while p15 and p21 were upregulated. Lowered expression of ZEB2 enhanced E-cadherin levels but also inhibited β-Catenin, Vimentin, N-cadherin, and Snail expression. Several apoptosis-related regulators such as Caspase-3, Caspase-6, Caspase-9, and Cleaved-PARP were activated while PARP was inhibited after ZEB2 siRNA treatment. CONCLUSION: Overexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells