Polyelectrolyte Bilayer-Based Transparent and Flexible Memristor for Emulating Synapses.

Memristors will be critical components in the next generation of digital technology and artificial synapses. Researchers are investigating innovative mechanistic understanding of the memristor devices based on low-cost, solution-processable, and organic materials as promising candidates. Here, we demonstrate a novel polyelectrolyte-based memristor device, which is simply prepared by spin-coating poly(acrylic acid) (PAA) and polyethylenimine (PEI) on an indium tin oxide (ITO) substrate followed by a magnetron sputtering of the ITO as the top electrode.

Neuroprotective effects of aucubin on hydrogen peroxide-induced toxicity in human neuroblastoma SH-SY5Y cells via the Nrf2/HO-1 pathway.

Background: When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis.

Purpose: The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (HO)-induced injury in SH-SY5Y cells in vitro.

Icariin reduces Glu-induced excitatory neurotoxicity via antioxidative and antiapoptotic pathways in SH-SY5Y cells.

Excessive glutamate (Glu) can lead to significant effects on neural cells through the generation of neurotoxic or excitotoxic cascades. Icariin (ICA) is a main active ingredient of Chinese Medicine Berberidaceae epimedium L., and has many biological activities, such as antiinflammation, antioxidative stress, and anti-depression.

Paeoniflorin ameliorates depressive-like behavior in prenatally stressed offspring by restoring the HPA axis- and glucocorticoid receptor- associated dysfunction.

Background: Prenatal stress (PS) can increase the risk of nervous, endocrine and metabolic diseases and induce depression in offspring. Paeoniflorin (PA) is an amorphous glucoside isolated from the aqueous extract of roots of the peony plant (Paeonia lactiflora Pall.) and exerts various pharmacological effects in the nervous system.

Imperatorin ameliorates learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling in prenatally-stressed female offspring.

Prenatal stress (PS) can lead to impaired spatial learning and memory in offspring. Imperatorin (IMP) is a naturally occurring furanocoumarin with many pharmacological properties. However, the effects of IMP on cognitive impairment induced by PS and the underlying molecular mechanisms remain unclear.

Icariin ameliorates learning and memory impairments through ERK/CaMKIIα/CREB signaling and HPA axis in prenatally stressed female offspring.

Background: Prenatal stress (PS) leads to a wide variety of behavioral and emotional aberration observed in later life, particularly in the impairment of spatial learning and memory in offspring. Icariin (ICA) is a naturally occurring furanocoumarin and exhibits many pharmacological properties, including potent improvement on learning and memory.

Purpose: We pretend to investigate the improvement of ICA on learning and memory impairment in PS.

Impact of fertilization on ammonia volatilization and NO emissions in an open vegetable field.

A field experiment with different nitrogen fertilization rates and mitigation measures was conducted in an open-ground vegetable field on the North China Plain to investigate the effects of nitrogen application level and management practices on ammonia volatilization and NO emission. Reducing the nitrogen fertilization rate by 20% and by 50% decreased ammonia volatilization by 25.7% and 48.

Copine-6 Binds to SNAREs and Selectively Suppresses Spontaneous Neurotransmission.

Recent studies suggest that spontaneous and action potential-evoked neurotransmitter release processes are independently regulated. However, the mechanisms that uncouple the two forms of neurotransmission remain unclear. In cultured mouse and rat neurons, we show that the two C2 domain-containing protein copine-6 is localized to presynaptic terminals and binds to synaptobrevin2 as well as other SNARE proteins in a Ca-dependent manner.

Active nuclear import and passive nuclear export are the primary determinants of TDP-43 localization.

ALS (Amyotrophic Lateral Sclerosis) is a neurodegenerative disease characterized by the redistribution of the RNA binding protein TDP-43 in affected neurons: from predominantly nuclear to aggregated in the cytosol. However, the determinants of TDP-43 localization and the cellular insults that promote redistribution are incompletely understood. Here, we show that the putative Nuclear Export Signal (NES) is not required for nuclear egress of TDP-43.

Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties.

Pertuzumab is an antihuman HER2 antibody developed for HER2 positive breast cancer. Glycosylation profiles are always the important issue for antibody based therapy. Previous findings have suggested the impact of glycosylation profiles on the function of antibodies, like pharmacodynamics, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets.

Presynaptic nerve terminals are highly specialized vesicle-trafficking machines. Neurotransmitter release from these terminals is sustained by constant local recycling of synaptic vesicles independent from the neuronal cell body. This independence places significant constraints on maintenance of synaptic protein complexes and scaffolds.

Synaptotagmin-1- and Synaptotagmin-7-Dependent Fusion Mechanisms Target Synaptic Vesicles to Kinetically Distinct Endocytic Pathways.

Synaptic vesicle recycling is essential for maintaining normal synaptic function. The coupling of exocytosis and endocytosis is assumed to be Ca dependent, but the exact role of Ca and its key effector synaptotagmin-1 (syt1) in regulation of endocytosis is poorly understood. Here, we probed the role of syt1 in single- as well as multi-vesicle endocytic events using high-resolution optical recordings.

Establishment of a fluorescence-based method to evaluate endocytosis of desialylated glycoproteins in vitro.

Insufficient sialylation can result in rapid clearance of therapeutic glycoproteins by intracellular degradation, which is mainly mediated by asialoglycoprotein receptors (ASGPRs) on hepatic cells. In contrast, for glycoproteins, a long half-life is often related to high level of terminal sialic acid. These could be extremely important for insufficient sialylated biomedicines in clinic, and development of therapeutic glycoproteins in laboratory.

How Do RIM-BPs Link Voltage-Gated Ca(2+) Channels to Evoked Neurotransmitter Release?

Coupling between voltage-gated Ca(2+) influx and synaptic vesicle exocytosis is essential for rapid evoked neurotransmission. Acuna et al. show that the knockout of RIM-BPs, which are key structural components of this coupling, decreases the reliability of evoked neurotransmitter release.

The OPN gene polymorphism confers the susceptibility and response to Ara-C based chemotherapy in Chinese AML patients.

Aim: To investigate the possible association between the Osteopontin (OPN) gene polymorphisms and the susceptibility and chemotherapy response of acute myeloid leukemia patients.

Methods: A total of 381 patients with de nova AML and 430 healthy controls were enrolled. All patients received Ara-C-based standard induction chemotherapy regimens, and the treatment response was evaluated.

Changes in portal hemodynamics after TIPS in liver cirrhosis and portal hypertension.

Objective: The objective of this study is to analyze the changes in portal hemodynamics that occurs in portal hypertension before and after transjugular intrahepatic portosystemic shunt (TIPS), to investigate the relationship between these changes and portal pressure (PP) and to determine the significance of sonographic parameters in measuring PP.

Methods: Ultrasonography of the portal and splenic veins and direct measurement of the PP were performed in 92 patients before and after TIPS. The differences observed in the portal and splenic vein diameters, the blood flow velocity in the portal and splenic veins and the PP were measured, and the correlations between PP and the other parameters were assessed using the SPSS 13 (SPSS Inc.

VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission.

Synaptic vesicles in the brain harbor several soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) proteins. With the exception of synaptobrevin2, or VAMP2 (syb2), which is directly involved in vesicle fusion, the role of these SNAREs in neurotransmission is unclear. Here we show that in mice syb2 drives rapid Ca(2+)-dependent synchronous neurotransmission, whereas the structurally homologous SNARE protein VAMP4 selectively maintains bulk Ca(2+)-dependent asynchronous release.

I(h) "run-up" in rat neocortical neurons and transiently rat or human HCN1-expressing HEK293 cells.

Hyperpolarization-activated cyclic nucleotide-gated ion channels (HCN) are key determinants of CNS functions. Here we describe an increase in hyperpolarization-activated current (I(h)) at the beginning of whole-cell recordings in rat layer 5 cortical neurons. For a closer investigation of this I(h) increase, we overexpressed the predominant layer 5 rat subunit HCN1 in HEK293 cells.

Laparoscopic splenectomy and periesophagogastric devascularization with endoligature for portal hypertension in children.

Background: Bleeding from esophagogastric varices is an importment complication of portal hypertension. Recently, significant progress in laparoscopic technology has enabled the devascularization of the lower esophagus and upper stomach in a less invasive way. In this article, we report our preliminary experience with laparoscopic splenectomy and periesophagogastric devascularization by endoligature and its effectiveness for bleeding varices with hypersplenism in children.

Cholesterol depletion induces anoikis-like apoptosis via FAK down-regulation and caveolae internalization.

Caveolae (lipid rafts), microdomains of the plasma membrane, are known to contain various signalling molecules and consequently are involved in the regulation of many biological functions. To investigate the role of the caveolae in cell survival and adhesion, we disrupted the caveolae by depletion of cholesterol, a major lipid component of the caveolae, with methyl-beta cyclodextrin (MbetaCD) treatment of A431 cells. We found that cholesterol depletion induced an anoikis-like cell death involving actin reorganization, resulting in a decrease in cell spreading and an increase in cell detachment, which was reversed by cholesterol addition.

Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents.

Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-beta cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation.