Inhibition of Heat Shock Protein 90 by 17-AAG Reduces Inflammation via P2X7 Receptor/NLRP3 Inflammasome Pathway and Increases Neurogenesis After Subarachnoid Hemorrhage in Mice

Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular disease that usually has a poor prognosis. Heat shock proteins (HSPs) have been implicated in the mechanisms of SAH-associated damage, including increased inflammation and reduced neurogenesis. The aim of this study was to investigate the effects of HSP90 inhibition on inflammation and neurogenesis in a mouse model of experimental SAH induced by endovascular surgery. Western blotting showed HSP90 levels to be decreased, while neurogenesis, evaluated by 5-bromo-2’-deoxyuridine (BrdU) immunohistochemistry, was decreased in the hippocampuses of SAH mice. SAH also induced pro-inflammatory factors such as interleukin-1β (IL-1β), capase-1 and the NLRP3 inflammasome. However, intraperitoneal administration of the specific HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) reduced the levels of HSP90, NLRP3, ASC, caspase-1 and IL-1β, while increasing the levels of brain-derived neurotrophic factor and doublecortin (DCX), as well as the number of BrdU-positive cells in SAH mice. In addition, 17-AGG improved short- and long-term neurobehavioral outcomes. The neuroprotective and anti-inflammatory effects of 17-AGG were reversed by recombinant HSP90 (rHSP90); this detrimental effect of HSP90 was inhibited by the specific P2X7 receptor (P2X7R) inhibitor A438079, indicating that SAH-induced inflammation and inhibition of neurogenesis were likely mediated by HSP90 and the P2X7R/NLRP3 inflammasome pathway. HSP90 inhibition by 17-AAG may be a promising therapeutic strategy for the treatment of SAH

The effect of extended hours dialysis on sleep quality in a randomised trial

Poor sleep quality is common in haemodialysis patients and associated with worse outcomes. In this pre-specified analysis, we examined the impact of extended hours haemodialysis on sleep quality.The ACTIVE Dialysis trial randomized 200 participants to extended (≥24 hours/week) or standard (target 12-15 hours) hours haemodialysis over 12 months. Sleep quality was measured in the Kidney Disease Quality of Life Short Form 1.3 (KDQOL-SF) by overall sleep quality score (0-10, 10 = "very good") and the sleep subscale (0-100, 100 = 'best possible sleep') every three months via blinded telephone interviewer. The average intervention effect was calculated by mixed linear regression adjusted by time point and baseline score. Factors predicting sleep quality were assessed by multivariate regression analysis.Overall sleep quality score and sleep subscale at baseline were similar in both groups (5.9 [95%CI 5.4-6.4] vs 6.3 [5.9-6.8]; 65.0 [60.9-69.1] vs 63.2 [59.1-67.3]; extended and standard hours respectively). Extended hours haemodialysis led to a non-significant improvement in overall sleep quality score (average intervention effect 0.44 (-0.01-0.89), p=0.053) and sleep subscale (average intervention effect 3.58 (-0.02-7.18), p= 0.051). Poor sleep quality was associated with being female and with current smoking. Sleep quality was positively associated with EuroQol-5D (EQ5D) and the SF-36 Physical Component and Mental Component Summary Scores but not with hospitalisations.Sleep quality was not significantly improved by extended hours dialysis in this study. Sleep quality is positively correlated with quality of life in haemodialysis patients and is poorer in women and current smokers

Disrupted Functional Brain Connectivity in Partial Epilepsy: A Resting-State fMRI Study

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy

Observation of χc1\chi_{c1} decays into vector meson pairs ϕϕ\phi\phi, ωω\omega\omega, and ωϕ\omega\phi

Decays of $\chi_{c1}$ to vector meson pairs $\phi\phi$, $\omega\omega$ and $\omega\phi$ are observed for the first time using $(106\pm4)\times 10^6$ \psip events accumulated at the BESIII detector at the BEPCII $e^+e^-$ collider. The branching fractions are measured to be $(4.4\pm 0.3\pm 0.5)\times 10^{-4}$, $(6.0\pm 0.3\pm 0.7)\times 10^{-4}$, and $(2.2\pm 0.6\pm 0.2)\times 10^{-5}$, for $\chi_{c1}\to \phi\phi$, $\omega\omega$, and $\omega\phi$, respectively. The observation of $\chi_{c1}$ decays into a pair of vector mesons $\phi\phi$, $\omega\omega$ and $\omega\phi$ indicates that the hadron helicity selection rule is significantly violated in $\chi_{cJ}$ decays. In addition, the measurement of $\chi_{cJ}\to \omega\phi$ gives the rate of doubly OZI-suppressed decay. Branching fractions for $\chi_{c0}$ and $\chi_{c2}$ decays into other vector meson pairs are also measured with improved precision.Comment: 4 pages, 2 figure

Precision measurement of the branching fractions of J/psi -> pi+pi-pi0 and psi' -> pi+pi-pi0

We study the decays of the J/psi and psi' mesons to pi+pi-pi0 using data samples at both resonances collected with the BES III detector in 2009. We measure the corresponding branching fractions with unprecedented precision and provide mass spectra and Dalitz plots. The branching fraction for J/psi -> pi+pi-pi0 is determined to be (2.137 +- 0.004 (stat.) +0.058-0.056 (syst.) +0.027-0.026 (norm.))*10-2, and the branching fraction for psi' -> pi+pi-pi0 is measured as (2.14 +- 0.03 (stat.) +0.08-0.07 (syst.) +0.09-0.08 (norm.))*10-4. The J/psi decay is found to be dominated by an intermediate rho(770) state, whereas the psi' decay is dominated by di-pion masses around 2.2 GeV/c2, leading to strikingly different Dalitz distributions.Comment: 15 pages, 2 figure

First Observation of the Decays chi_{cJ} -> pi^0 pi^0 pi^0 pi^0

We present a study of the P-wave spin -triplet charmonium chi_{cJ} decays (J=0,1,2) into pi^0 pi^0 pi^0 pi^0. The analysis is based on 106 million \psiprime decays recorded with the BESIII detector at the BEPCII electron positron collider. The decay into the pi^0 pi^0 pi^0 pi^0 hadronic final state is observed for the first time. We measure the branching fractions B(chi_{c0} -> pi^0 pi^0 pi^0 pi^0)=(3.34 +- 0.06 +- 0.44)*10^{-3}, B(chi_{c1} -> pi^0 pi^0 pi^0 pi^0)=(0.57 +- 0.03 +- 0.08)*10^{-3}, and B(chi_{c2} -> pi^0 pi^0 pi^0 pi^0)=(1.21 +- 0.05 +- 0.16)*10^{-3}, where the uncertainties are statistical and systematical, respectively.Comment: 7 pages, 3 figure

Study of J/ψ→ppˉJ/\psi\to p\bar{p} and J/ψ→nnˉJ/\psi\to n\bar{n}

The decays $J/\psi\to p\bar{p}$ and $J/\psi\to n\bar{n}$ have been investigated with a sample of 225.2 million $J/\psi$ events collected with the BESIII detector at the BEPCII $e^+e^-$ collider. The branching fractions are determined to be $\mathcal{B}(J/\psi\to p\bar{p})=(2.112\pm0.004\pm0.031)\times10^{-3}$ and $\mathcal{B}(J/\psi\to n\bar{n})=(2.07\pm0.01\pm0.17)\times10^{-3}$. Distributions of the angle $\theta$ between the proton or anti-neutron and the beam direction are well described by the form $1+\alpha\cos^2\theta$, and we find $\alpha=0.595\pm0.012\pm0.015$ for $J/\psi\to p\bar{p}$ and $\alpha=0.50\pm0.04\pm0.21$ for $J/\psi\to n\bar{n}$. Our branching-fraction results suggest a large phase angle between the strong and electromagnetic amplitudes describing the $J/\psi\to N\bar{N}$ decay.Comment: 16 pages, 13 figures, the 2nd version, submitted to PR

Giant regular polyhedra from calixarene carboxylates and uranyl

Self-assembly of large multi-component systems is a common strategy for the bottom-up construction of discrete, well-defined, nanoscopic-sized cages. Icosahedral or pseudospherical viral capsids, built up from hundreds of identical proteins, constitute typical examples of the complexity attained by biological self-assembly. Chemical versions of the so-called 5 Platonic regular or 13 Archimedean semi-regular polyhedra are usually assembled combining molecular platforms with metals with commensurate coordination spheres. Here we report novel, self-assembled cages, using the conical-shaped carboxylic acid derivatives of calix[4]arene and calix[5]arene as ligands, and the uranyl cation UO22+ as a metallic counterpart, which coordinates with three carboxylates at the equatorial plane, giving rise to hexagonal bipyramidal architectures. As a result, octahedral and icosahedral anionic metallocages of nanoscopic dimensions are formed with an unusually small number of components

First observation of the M1 transition ψ(3686)→γηc(2S)\psi(3686)\to \gamma\eta_c(2S)

Using a sample of 106 million \psi(3686) events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium S-wave spin-triplet and the radially excited S-wave spin-singlet states: \psi(3686)\to\gamma\eta_c(2S). Analyses of the processes \psi(2S)\to \gamma\eta_c(2S) with \eta_c(2S)\to \K_S^0 K\pi and K^+K^-\pi^0 gave an \eta_c(2S) signal with a statistical significance of greater than 10 standard deviations under a wide range of assumptions about the signal and background properties. The data are used to obtain measurements of the \eta_c(2S) mass (M(\eta_c(2S))=3637.6\pm 2.9_\mathrm{stat}\pm 1.6_\mathrm{sys} MeV/c^2), width (\Gamma(\eta_c(2S))=16.9\pm 6.4_\mathrm{stat}\pm 4.8_\mathrm{sys} MeV), and the product branching fraction (\BR(\psi(3686)\to \gamma\eta_c(2S))\times \BR(\eta_c(2S)\to K\bar K\pi) = (1.30\pm 0.20_\mathrm{stat}\pm 0.30_\mathrm{sys})\times 10^{-5}). Combining our result with a BaBar measurement of \BR(\eta_c(2S)\to K\bar K \pi), we find the branching fraction of the M1 transition to be \BR(\psi(3686)\to\gamma\eta_c(2S)) = (6.8\pm 1.1_\mathrm{stat}\pm 4.5_\mathrm{sys})\times 10^{-4}.Comment: 7 pages, 1 figure, 1 tabl

Study of χcJ\chi_{cJ} radiative decays into a vector meson

The decays $\chi_{cJ}\to\gamma V$ ($V=\phi, \rho^0, \omega$) are studied with a sample of radiative \psip\to\gamma\chi_{cJ} events in a sample of (1.06\pm0.04)\times 10^{8} \psip events collected with the BESIII detector. The branching fractions are determined to be: ${\cal B}(\chi_{c1}\to \gamma\phi)=(25.8\pm 5.2\pm 2.3)\times 10^{-6}$, ${\cal B}(\chi_{c1}\to \gamma\rho^0)=(228\pm 13\pm 22)\times 10^{-6}$, and ${\cal B}(\chi_{c1}\to \gamma\omega)=(69.7\pm 7.2\pm 6.6)\times 10^{-6}$. The decay $\chi_{c1}\to \gamma\phi$ is observed for the first time. Upper limits at the 90% confidence level on the branching fractions for $\chi_{c0}$ and \chict decays into these final states are determined. In addition, the fractions of the transverse polarization component of the vector meson in $\chi_{c1}\to \gamma V$ decays are measured to be $0.29_{-0.12-0.09}^{+0.13+0.10}$ for $\chi_{c1}\to \gamma\phi$, $0.158\pm 0.034^{+0.015}_{-0.014}$ for $\chi_{c1}\to \gamma\rho^0$, and $0.247_{-0.087-0.026}^{+0.090+0.044}$ for $\chi_{c1}\to \gamma\omega$, respectively. The first errors are statistical and the second ones are systematic.Comment: 8 pages, 3 figure