MRI signal intensity differentiation of brainstem encephalitis induced by Enterovirus 71: a classification approach for acute and convalescence stages

Additional file 3. After tick the segment region, Medflovan show the segmentation region of lesion

New Findings, Classification and Long-Term Follow-Up Study Based on MRI Characterization of Brainstem Encephalitis Induced by Enterovirus 71

Background To report the diversity of MRI features of brainstem encephalitis (BE) induced by Enterovirus 71. This is supported by implementation and testing of our new classification scheme in order to improve the diagnostic level on this specific disease. Methods Neuroimaging of 91 pediatric patients who got EV71 related BE were hospitalized between March, 2010 to October, 2012, were analyzed retrospectively. All patients underwent pre- and post-contrast MRI scan. Thereafter, 31 patients were randomly called back for follow-up MRI study during December 2013 to August 2014. The MRI signal patterns of BE primary lesion were analyzed and classified according to MR signal alteration at various disease stages. Findings in fatal and non-fatal cases were compared, and according to the MRI scan time point during the course of this disease, the patients’ conditions were classified as 1) acute stage, 2) convalescence stage, 3) post mortem stage, and 4) long term follow-up study. Results 103 patients were identified. 11 patients did not undergo MRI, as they died within 48 hours. One patient died on 14th day without MR imaging. 2 patients had postmortem MRI. Medical records and imaging were reviewed in the 91 patients, aged 4 months to 12 years, and two cadavers who have had MRI scan. At acute stage: the most frequent pattern (40 patients) was foci of prolonged T1 and T2 signal, with (15) or without (25) contrast enhancement. We observed a novel pattern in 4 patients having foci of low signal intensity on T2WI, with contrast enhancement. Another pattern in 10 patients having foci of contrast enhancement without abnormalities in T1WI or T2WI weighted images. Based on 2 cases, the entire medulla and pons had prolonged T1 and T2 signal, and 2 of our postmortem cases demonstrated the same pattern. At convalescence stage, the pattern observed in 4 patients was foci of prolonged T1 and T2 signal without contrast enhancement. Follow-up MR study of 31 cases showed normal in 26 cases, and demonstrated foci of prolonged T1 and T2 signal with hyper-intensity on FLAIR in 3 cases, or of prolonged T1 and T2 signal with hypo-intensity on FLAIR in 2 cases. Most importantly, MR findings of each case were thoroughly investigated and classified according to phases and MRI signal alteration. Conclusions This study has provided enhanced and useful information for the MRI features of BE induced by EV71, apart from common practice established by previous reports. In addition, a classification scheme that summarizes all types of features based on the MRI signal at the four different stages of the disease would be helpful to improve the diagnostic level

Pathological Role of Peptidyl-Prolyl Isomerase Pin1 in the Disruption of Synaptic Plasticity in Alzheimer’s Disease

Synaptic loss is the structural basis for memory impairment in Alzheimer’s disease (AD). While the underlying pathological mechanism remains elusive, it is known that misfolded proteins accumulate as β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles decades before the onset of clinical disease. The loss of Pin1 facilitates the formation of these misfolded proteins in AD. Pin1 protein controls cell-cycle progression and determines the fate of proteins by the ubiquitin proteasome system. The activity of the ubiquitin proteasome system directly affects the functional and structural plasticity of the synapse. We localized Pin1 to dendritic rafts and postsynaptic density (PSD) and found the pathological loss of Pin1 within the synapses of AD brain cortical tissues. The loss of Pin1 activity may alter the ubiquitin-regulated modification of PSD proteins and decrease levels of Shank protein, resulting in aberrant synaptic structure. The loss of Pin1 activity, induced by oxidative stress, may also render neurons more susceptible to the toxicity of oligomers of Aβ and to excitation, thereby inhibiting NMDA receptor-mediated synaptic plasticity and exacerbating NMDA receptor-mediated synaptic degeneration. These results suggest that loss of Pin1 activity could lead to the loss of synaptic plasticity in the development of AD

Synthesis, cytotoxicity and proteomics studies of artemisinin derivatives

abstractpublished_or_final_versionChemistryDoctoralDoctor of Philosoph

Effect of divalent metals on phytase activity and enzymatic kinetics of As-hyperaccumulation ferns

Phytase secreted by plant roots can hydrolyse phytate to provide phosphorus (P) for plants growth. To ensure the plant growth and to reduce the pollution caused by heavy metal in environment, this paper studies the phytase activity in environment. The activity of phytase in the environment is directly related to the bioavailability of phytate. The catalytic reaction between phytase and phytate is affected by divalent metal ions in the environment, due to Zn2+, Cu2+, Fe2+ and Ca2+ can easy to form a stable chelate with phytate. Through the enzymatic kinetic equations, Zn2+ and Ca2+ can cause conformational changes of enzyme molecules, resulting in catalytic function loss, and partial competition between Cu2+/Fe2+ and substrates can affect the catalytic efficiency of phytase. The results showed that the effects of different divalent metal ions on phytase activity were Zn2+ > Cu2+ > Fe2+ > Ca2+. The phytase activity showed twice-inhibition after interacting others divalent metal ions with Ca2+ and existed the enlarge inhibition effect between Zn2+/Cu2+ and Ca2+, but there was an antagonistic effect between Fe2+ and Ca2+, which may be related to the replacement ability between different divalent metal ions and the ability of binding phytase

Acoustic guided-mode resonances in a metamaterial

We theoretically analyze and numerically demonstrate that guided-mode resonance (GMR) effects can be achieved in acoustic systems. Similar to its optical counterpart, the acoustic GMR-like effects can support multiple narrow bandwidth transmission dips at a broad range of frequencies and give rise to strongly localized acoustic pressure fields in the acoustic waveguide layer. The discussed fundamental phenomena will allow a broad range of applications, including the design of filters, sensors, and other novel acoustic devices

Discovery of Novel Small-Molecule Inhibitors of PD-1/PD-L1 Interaction via Structural Simplification Strategy

Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-molecule inhibitors of PD-1/PD-L1 pathways. Even though many small-molecule inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small molecules. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC50 = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (KD = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-positive T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study

Nonheme Iron-Mediated Amination of C(sp³)–H Bonds. Quinquepyridine-Supported Iron-Imide/Nitrene Intermediates by Experimental Studies and DFT Calculations

The 7-coordinate complex [Fe­(qpy)­(MeCN)₂]­(ClO₄)₂ (<b>1</b>, qpy = 2,2′:6′,2″:6″,2′′′:6′′′,2′′′′-quinquepyridine) is a highly active nonheme iron catalyst for intra- and intermolecular amination of C­(sp³)–H bonds. This complex effectively catalyzes the amination of limiting amounts of not only benzylic and allylic C­(sp³)–H bonds of hydrocarbons but also the C­(sp³)–H bonds of cyclic alkanes and cycloalkane/linear alkane moieties in sulfamate esters, such as those derived from menthane and steroids cholane and androstane, using PhINR or “PhI­(OAc)₂ + H₂NR” [R = Ts (<i>p</i>-toluenesulfonyl), Ns (<i>p</i>-nitrobenzenesulfonyl)] as nitrogen source, with the amination products isolated in up to 93% yield. Iron imide/nitrene intermediates [Fe­(qpy)­(NR)­(X)]^<i>n</i>+ (<b>C</b>_<b>X</b>, X = NR, solvent, or anion) are proposed in these amination reactions on the basis of experimental studies including ESI-MS analysis, crossover experiments, Hammett plots, and correlation with C–H bond dissociation energies and with support by DFT calculations. Species consistent with the formulations of [Fe­(qpy)­(NTs)₂]²⁺ (<b>C</b>_<b>NTs</b>) and [Fe­(qpy)­(NTs)]²⁺ (<b>C</b>) were detected by high-resolution ESI-MS analysis of the reaction mixture of <b>1</b> with PhINTs (4 equiv). DFT calculations revealed that the reaction barriers for H-atom abstraction of cyclohexane by the ground state of 7-coordinate <b>C</b>_<b>NTs</b> and ground state of <b>C</b> are 15.3 and 14.2 kcal/mol, respectively, in line with the observed high activity of <b>1</b> in catalyzing the C–H amination of alkanes under mild conditions