Zinc Accumulation Aggravates Cerebral Ischemia/Reperfusion Injury Through Inducing Endoplasmic Reticulum Stress.

Zinc is highly enriched in the central nervous system. Numerous evidences suggest that high concentration of zinc acts as a critical mediator of neuronal death in the ischemic brain, however, the possible mechanisms of neurotoxicity of zinc during cerebral ischemia/reperfusion (I/R) remain elusive. Endoplasmic reticulum (ER) is a storage location of intracellular zinc. ER stress related genes were up-regulated during zinc-induced neuronal death in vascular-type senile dementia. In the present study, we investigated whether intracellular accumulated zinc aggravates I/R injury through ER stress and ER stress-associated apoptosis. Male Sprague-Dawley rats were subjected to 90 min middle cerebral artery occlusion (MCAO) and received either vehicle or zinc chelator TPEN 15 mg/kg. The expression of ER stress related factors glucose-regulated protein 78 (GRP78) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α), ER stress related apoptotic proteins CCAAT-enhancer-binding protein homologous protein (CHOP) and caspase-12, as well as anti-apoptotic factor B-cell lymphoma-2 (Bcl-2) were assessed 24 h after reperfusion. Our results showed that the levels of GRP78 and p-eIF2α, as well as CHOP and caspase-12, were increased in ischemic brain, indicating that cerebral I/R triggers ER stress. Furthermore, GRP78, CHOP and caspase-12 were all colocalized with the zinc-specific dyes NG, suggesting that there is certain relationship between cytosolic labile zinc and ER stress following cerebral ischemia. Chelating zinc with TPEN reversed the expression of GRP78, p-eIF2α in ischemic rats. Moreover, CHOP and NeuN double staining positive cells, as well as caspase-12 and TUNEL double staining positive cells were also decreased after TPEN treatment, indicating that chelating zinc might inhibit ER stress and decreased ER stress associated neuronal apoptosis. In addition, TPEN treatment reversed the downregulated level of Bcl-2, which localized in the ER membrane and involved in the dysfunction of ER, confirming that the anti-apoptosis effects of chelating zinc following I/R are exerted via inhibition of the ER stress. Taken together, this study demonstrated that excessive zinc activates ER stress and zinc induced neuronal cell death is at least partially due to ER stress specific neuronal apoptosis in ischemic penumbra, which may provide an important mechanism of cerebral I/R injury.

Highly sensitive and multiplexed miRNA analysis based on digitally encoded silica microparticles coupled with RCA-based cascade amplification.

Currently, miRNA analysis is significant for understanding miRNA regulation networks and clinical diagnostics and therapy. Analytical strategies feasible for multiplex miRNA-sensitive analysis are still in high demand. Herein, we propose a novel strategy for miRNA analysis by coupling cascade amplification with digitally encoded silica microparticles. The microparticles are precisely fabricated in a digital form through a one-step deposition strategy and are highly efficient for multiplex analysis. The cascade amplification composed of RCA and nicking-assisted strand-displacement amplification (SDA) exhibits high amplification efficiency and requires no complicated sequence design, thus improving the compatibility with base-stacking hybridization on our microparticles. Parallel and sensitive analyses for let-7a and miR-21 in one pot without mutual interference have been achieved with both high sensitivity (LOD, ∼0.5 fM) and wide dynamic range (10 pM-1 fM). Moreover, our strategy exhibits high specificity for miRNAs of homologous sequence and good anti-interference ability in a complex sample matrix. Considering that there are up to 128 (27) kinds of microparticles available, our strategy can be applied for dozens of miRNA-sensitive analyses in one pot, and it has great potential for miRNA signature analysis as well as widespread clinical applications.

A New Variational Bayesian Adaptive Extended Kalman Filter for Cooperative Navigation.

To solve the problem of unknown state noises and uncertain measurement noises inherent in underwater cooperative navigation, a new Variational Bayesian (VB)-based Adaptive Extended Kalman Filter (VBAEKF) for master⁻slave Autonomous Underwater Vehicles (AUV) is proposed in this paper. The Inverse Wishart (IW) distribution is used to model the predicted error covariance and measurement noise covariance matrix. The state, together with the predicted error covariance and measurement noise covariance matrix, can be adaptively estimated based on VB approximation. The performance of the proposed algorithm is demonstrated through a lake trial, which shows the advantage of the proposed algorithm.

Reabsorption of intervertebral disc prolapse after conservative treatment with traditional Chinese medicine: A case report.

BACKGROUND: Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation (LIDH) within a few weeks. CASE SUMMARY: Computed tomography and magnetic resonance imaging (MRI) of the lumbar region of a 25-year-old male diagnosed with LIDH showed prolapse of the L5/S2 disc. The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge. The patient elected a conservative treatment regimen that included traditional Chinese medicine (TCM), acupuncture, and massage. During a follow-up period of more than 12 mo, good improvement in pain was reported without complications. MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation. CONCLUSION: A conservative treatment regimen of TCM, acupuncture, and massage promoted reabsorption of a prolapsed disc.