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Sustaining the steady state for highly active non‐stoichiometric iridium (Ir)‐based oxide (IrOx) at low Ir loading remains challenging primarily due to the continuous oxidation and sequent dissolution of Ir active sites during the oxygen evolution reaction (OER). In this context, a new iridium–cerium (Ce) substitution solid solution oxide (SSO) has been developed, featuring uniformly dispersed Ir atoms within Ce dioxide (CeO2) matrix as electron buffer, which delivers remarkable acidic OER catalytic activity and enhanced stability. The electron‐buffering capacity of CeO2 facilitates the charge transfer toward Ir atoms, leading to abundant active low‐valence Ir sites and effectively prevent their oxidation and dissolution. As a result, Ir─Ce SSO demonstrates an overpotential of merely 238 mV@10 mA cm−2. Proton exchange membrane water electrolyzer employing Ir─Ce SSO at a low Ir loading of 396 µgIr cm−2 operates consistently for over 100 h@500 mA cm−2. Density functional theory (DFT) calculations corroborate that the electron‐buffering effect of CeO2 enriches the density of IrIII and substantially increases the dissolution energy barrier of Ir atoms. This study presents a viable approach to addressing the issues of instability and low efficiency in Ir‐based OER electrocatalysts for acidic water electrolysis. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with symptoms including social deficits, anxiety, and communication difficulties. However, ASD pathogenic mechanisms are poorly understood. Mutations of CUL3 , which encodes Cullin 3 (CUL3), a component of an E3 ligase complex, are thought of as risk factors for ASD and schizophrenia (SCZ). CUL3 is abundant in the brain, yet little is known of its function. Here, we show that CUL3 is critical for neurodevelopment. CUL3-deficient mice exhibited social deficits and anxiety-like behaviors with enhanced glutamatergic transmission and neuronal excitability. Proteomic analysis revealed eIF4G1, a protein for Cap-dependent translation, as a potential target of CUL3. ASD-associated cellular and behavioral deficits could be rescued by pharmacological inhibition of the eIF4G1 function and chemogenetic inhibition of neuronal activity. Thus, CUL3 is critical to neural development, neurotransmission, and excitation-inhibition (E-I) balance. Our study provides novel insight into the pathophysiological mechanisms of ASD and SCZ. • Cul3 mutant mice exhibits social behavioral deficits and anxiety-like behaviors • CUL3 deficiency impairs neurotransmission, excitability, and E-I balance • Protein translation and synaptic vesicle turnover are increased in Cul3 mutant mice • Inhibiting protein translation rescues social behavior and neurotransmission deficits Mutations of CUL3 , a component of an E3 ligase complex, are thought of as risk factors for autism spectrum disorders (ASDs) and schizophrenia. Here, Dong et al. show CUL3 deficiency in mice causes social deficits and anxiety-like behaviors and enhances glutamatergic transmission and neuronal excitability. Proteomic analysis reveals eIF4G1, a protein for Cap-dependent translation, as a potential target of CUL3 deficiency. Pharmacological inhibition of eIF4G1 and chemogenetic inhibition of neuronal activity attenuates ASD-associated cellular and behavioral deficits. [ABSTRACT FROM AUTHOR]

The study investigated the effects of feed efficiency (residual feed intake, RFI and residual intake and gain, RIG) on the production performance of small-sized meat ducks. Ninety ducks with intermediate and extreme (high and low) RFI values were selected from 1,083 male ducks of similar body weight, and the 3 groups were then redivided according to RIG. For both efficiency measures, the feed conversion ratio (FCR) and average daily feed intake (ADFI) of efficient ducks were significantly lower than those of inefficient ducks (P < 0.05), while the residual body weight gain (RG) was significantly higher in efficient ducks (P < 0.05). Inefficient-RFI animals showed greater skin fat yield (P < 0.05), but no other differences in carcass traits were observed (P > 0.05). RIG had positive effects on the pH 1 value of the breast muscle (P < 0.05), but feed efficiency did not affect the other meat quality traits (P > 0.05). With regard to blood biochemical parameters, efficient ducks had significantly lower triglycerides (TG) (P < 0.05). Correlation analysis demonstrated that RFI was positively correlated with average daily feed intake and feed conversion ratio (P < 0.05), while RIG exhibited a strong negative correlation with both (P < 0.05). The average daily body weight gain was positively correlated with RIG (P < 0.05). RIG had a positive effect on the pH 1 value of the breast muscle (P < 0.05). Furthermore, triglyceride and high-density lipoprotein cholesterol levels correlated with both efficiency classifications (P < 0.05). Overall, the efficiency measures did not affect the carcass and meat quality of small-sized meat ducks but could identify ducks with lower feed consumption and fast growth. [ABSTRACT FROM AUTHOR]

Aims Opioid addiction is associated with long-term adaptive changes in the brain that involve protein expression. The carboxyl-terminal of the μ opioid receptor (MOR-C) is important for receptor signal transduction under opioid treatment. However, the proteins that interact with MOR-C after chronic morphine exposure remain unknown. The brain cDNA library of chronic morphine treatment rats was screened using rat MOR-C to investigate the regulator of opioids dependence in the present study. Main methods The brain cDNA library from chronic morphine-dependent rats was constructed using the SMART (Switching Mechanism At 5′ end of RNA Transcript) technique. Bacterial two-hybrid system was used to screening the rat MOR-C interacting proteins from the cDNA library. RT-qPCR and immunoblotting were used to determine the variation of MOR-C interacting proteins in rat brain after chronic morphine treatment. Column overlay assays, immunocytochemistry and coimmunoprecipitation were used to demonstrate the interaction of MOR-C and p75NTR-associated cell death executor (NADE). Key findings 21 positive proteins, including 19 known proteins were screened to interact with rat MOR-C. Expression of several of these proteins was altered in specific rat brain regions after chronic morphine treatment. Among these proteins, NADE was confirmed to interact with rat MOR-C by in vitro protein–protein binding and coimmunoprecipitation in Chinese hamster ovary (CHO) cells and rat brain with or without chronic morphine treatment. Significance Understanding the rat MOR-C interacting proteins and the proteins variation under chronic morphine treatment may be critical for determining the pathophysiological basis of opioid tolerance and addiction. [ABSTRACT FROM AUTHOR]

Heat perception enables acute avoidance responses to prevent tissue damage and maintain body thermal homeostasis. Unlike other modalities, how heat signals are processed in the spinal cord remains unclear. By single-cell gene profiling, we identified ErbB4, a transmembrane tyrosine kinase, as a novel marker of heat-sensitive spinal neurons in mice. Ablating spinal ErbB4+ neurons attenuates heat sensation. These neurons receive monosynaptic inputs from TRPV1+ nociceptors and form excitatory synapses onto target neurons. Activation of ErbB4+ neurons enhances the heat response, while inhibition reduces the heat response. We showed that heat sensation is regulated by NRG1, an activator of ErbB4, and it involves dynamic activity of the tyrosine kinase that promotes glutamatergic transmission. Evidence indicates that the NRG1-ErbB4 signaling is also engaged in hypersensitivity of pathological pain. Together, these results identify a spinal neuron connection consisting of ErbB4+ neurons for heat sensation and reveal a regulatory mechanism by the NRG1-ErbB4 signaling. [Display omitted] • Spinal ErbB4+ neurons are activated by heat and synapsed by TRPV1+ nociceptors • Heat sensation is reduced by ErbB4+ neuron ablation or inhibition • Augmented effect on heat sensation by inhibiting ErbB4+, SST+, and CCK+ neurons together • NRG1-ErbB4 signaling promotes heat sensation and hypersensitivity How heat signals are processed in the spinal cord remains unclear. Wang et al. found that ErbB4+ excitatory interneurons are activated by noxious heat, and they participate in heat sensation in mice. In addition, the neuregulin-ErbB4 signaling regulates heat sensation and contributes to heat hypersensitivity under pathological conditions. [ABSTRACT FROM AUTHOR]

A tunable and efficient strategy was adopted to synthesize highly porous nano-structured CuO−carbonized composites (CuxO@C) using Cu3(BTC)2 as a sacrificial template. The as-synthesized CuO nanocomposites exhibited hollow octahedral structures, a large surface area (89.837 m2 g−1) and a high proportion of Cu2O active sites distributed on a carbon frame. Based on DFT calculations, both the Cu atoms on the surface (CuS) and oxygen vacancy (OV) exhibited strong chemical reactivity. On the perfect CuO (111), the CuS transferred charge to O atoms on the surface and SO2 molecules. A strong adsorption energy (−1.41 eV) indicated the existence of the chemisorption process. On the oxygen-deficient CuO (111), the O2 preferably adsorbed on OV and then formed SO3 by bonding with SO2, followed by the cleavage of the O−O bond. Furthermore, the CuO nanocomposites exhibited an excellent ratio of S/Cu in SO2 removal experiments compared with CuO nanoparticles produced by coprecipitation. [ABSTRACT FROM AUTHOR]

ABSTRACT Thienorphine is a new nonselective partial agonist of opioid receptors, which is currently under a Phase II clinical trial in China as a new treatment for opioid dependence. In this study, we compared the effect of thienorphine with morphine on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of the rat dentate gyrus (DG). Furthermore, the effect of thienorphine on the synaptic structure of the CA1 hippocampal region and the expression of synaptophysin was investigated. Results indicated interesting differences between thienorphine and morphine on the modulation of hippocampal synaptic plasticity. Chronic thienorphine treatment facilitated LTP in the LPP-DG cell synapses more than chronic morphine treatment. Morphometric measurement and analysis showed that chronic thienorphine administration decreased the length of the active zone and reduced the thickness of CA1 postsynaptic densities compared with the saline group (control), but were elevated compared with the morphine group. Furthermore, the expression of hippocampal synaptophysin was increased with chronic thienorphine administration but reduced with chronic morphine treatment. Taken together, our study clearly demonstrates that chronic thienorphine treatment enhances LTP, modulates hippocampal synaptic structure, and increases the expression of hippocampal synaptophysin. Therefore, further study is warranted to investigate thienorphine as a new treatment for opioid dependence. Synapse 67:779-785, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Trafficking of α‐Amino‐3–hydroxy‐5–methylisoxazole‐4–propionic acid (AMPA) receptors (AMPARs), mediated by AMPAR interacting proteins, enabled neurons to maintain tuning capabilities at rest or active state. α/β-Hydrolase domain-containing 6 (ABHD6), an endocannabinoid hydrolase, was an AMPAR auxiliary subunit found to negatively regulate the surface delivery of AMPARs. While ABHD6 was found to prevent AMPAR tetramerization in endoplasmic reticulum, ABHD6 was also reported to localize at postsynaptic site. Yet, the role of ABHD6 interacting with AMPAR at postsynaptic site, and the physiological significance of ABHD6 regulating AMPAR trafficking remains elusive. Here, we generated the ABHD6 knockout (ABHD6KO) mice and found that deletion of ABHD6 selectively enhanced AMPAR-mediated basal synaptic responses and the surface expression of postsynaptic AMPARs. Furthermore, we found that loss of ABHD6 impaired hippocampal long-term depression (LTD) and synaptic downscaling in hippocampal synapses. AMPAR internalization assays revealed that ABHD6 was essential for neuronal activity-dependent endocytosis of surface AMPARs, which is independent of ABHD6's hydrolase activity. The defects of AMPAR endocytosis and LTD are expressed as deficits in learning flexibility in ABHD6KO mice. Collectively, we demonstrated that ABHD6 is an endocytic accessory protein promoting AMPAR endocytosis, thereby contributes to the formation of LTD, synaptic downscaling and reversal learning. • Deletion of ABHD6 increases AMPAR-mediated basal synaptic responses in hippocampal CA1 neurons. • Deletion of ABHD6 impairs long-term depression in hippocampal Schaffer collateral pathway. • ABHD6 is required for homeostatic synaptic downscaling in cultured hippocampal neurons. • ABHD6 is essential for activity-dependent endocytosis of surface AMPARs. • ABHD6KO mice show deficits in reversal learning tests. [ABSTRACT FROM AUTHOR]

Dopamine (DA) transmission is critical to motivation, movement, and emotion. Unlike glutamatergic and GABAergic synapses, the development of DA synapses is less understood. We show that bassoon (BSN) clusters along DA axons in the core of nucleus accumbens (NAcc) were increased in neonatal stages and reduced afterward, suggesting DA synapse elimination. Remarkably, DA neuron-specific ablating neuregulin 3 (NRG3), a protein whose levels correlate with BSN clusters, increased the clusters and impaired DA release and behaviors related to DA transmission. An unbiased screen of transmembrane proteins with the extracellular domain (ECD) of NRG3 identified Caspr3 (contactin associate-like protein 3) as a binding partner. Caspr3 was enriched in striatal medium spiny neurons (MSNs). NRG3 and Caspr3 interact in trans , which was blocked by Caspr3-ECD. Caspr3 null mice displayed phenotypes similar to those in DAT- Nrg3 f/f mice in DA axonal BSN clusters and DA transmission. Finally, in vivo disruption of the NRG3-Caspr3 interaction increased BSN clusters. Together, these results demonstrate that DA synapse development is controlled by trans interaction between NRG3 in DA neurons and Caspr3 in MSNs, identifying a novel pair of cell adhesion molecules for brain circuit wiring. [Display omitted] • Correlation of NRG3 with DA axonal bassoon clusters during development • Ablation of NRG3 increased DA axonal bassoon clusters and DA transmission • Caspr3 interacts in trans with NRG3 in the striatum • Disruption of the NRG3-Caspr3 interaction increased DA bassoon clusters on MSNs Cui et al. show that Neuregulin3 in dopaminergic neurons interacts with Caspr3 from medium spiny neurons in trans and controls the development of dopaminergic axonal bassoon clusters. Disruption of this NRG3-Caspr3 interaction increases dopamine release and impairs the behaviors related to dopaminergic transmission. [ABSTRACT FROM AUTHOR]

• Several new hydrophobic deep eutectic solvents (DESs) were prepared • A high efficient microextraction method was developed based on hydrophobic DESs • Successfully used for the determination of bisphenols from food-contacted plastics • The proposed method was simple, efficient and environment-friendly As a new kind of green solvents for potential replacement of traditional volatile organic compounds, deep eutectic solvents (DESs) have been attracting more and more attention in various applications. In this work, three types of hydrophobic DESs were synthesized by simple mixing of trioctylmethyl ammonium chloride (used as hydrogen bond acceptor) with decanoic acid, ketoprofen and gemfibrozil (hydrogen bond donors), respectively, at different molar ratios. In order to evaluate the solvent characteristics of these DESs, some of the physical properties such as melting point, density, viscosity, and water contact angle were determined. Then, these hydrophobic DESs were used for the vortex-assisted liquid-liquid microextraction of bisphenol-type contaminants in water, followed by quantitative determination of bisphenols contents with high performance liquid chromatography (HPLC-FLD) coupled with fluorescence detection. For this purpose, four bisphenols, namely, 2, 2-bis(4-hydroxydiphenyl)propane (BPA), 2, 2-bis (4-hydroxyphenyl)butane (BPB), 4, 4′-(1-phenylethylidene)bisphenol (BPAP) and 4, 4′-cyclohexylidenebisphenol (BPZ) were selected as model contaminants. It was found that the enrichment factors of the proposed method were in the range from 97 to 112, depending on the structure of the analytes. Under optimal experimental conditions, the linearity ranges of the method varied from 0.3 to 700 µg L−1 with linear correlation coefficients (R2) higher than 0.996. The limit of detections (LODs) and limit of quantifications (LOQs) were in the range of 0.3-0.5 µg L−1 and 0.06-0.08 µg L−1, respectively. Furthermore, the developed method was successfully used in the extraction and determination of four bisphenols from food-contacted plastic samples. [ABSTRACT FROM AUTHOR]

Synapses are the connections between neurons in the central nervous system (CNS) or between neurons and other excitable cells in the peripheral nervous system (PNS), where electrical or chemical signals rapidly travel through one cell to another with high spatial precision. Synaptic analysis, based on synapse numbers and fine morphology, is the basis for understanding neurological functions and diseases. Manual analysis of synaptic structures in electron microscopy (EM) images is often limited by low efficiency and subjective bias. We developed a multifunctional synaptic analysis system based on several advanced deep learning (DL) models. The system achieved synapse counting in low-magnification EM images and synaptic ultrastructure analysis in high-magnification EM images. The synapse counting system based on ResNet18 and a Faster R-CNN model had a mean average precision (mAP) of 92.55%. For synaptic ultrastructure analysis, the Faster R-CNN model based on ResNet50 achieved a mAP of 91.60%, the DeepLab v3 + model based on ResNet50 enabled high performance in presynaptic and postsynaptic membrane segmentation with a global accuracy of 0.9811, and the Faster R-CNN model based on ResNet18 achieved a mAP of 91.41% for synaptic vesicle detection. The proposed multifunctional synaptic analysis system may help to overcome the experimental bias inherent in manual analysis, thereby facilitating EM image–based synaptic function studies. • DL models achieve high performance for synaptic analysis using EM images. • Faster R-CNN model achieved accurate synapse counting in low-magnification EM images. • Integration of multiple DL models enables efficient synaptic ultrastructure analysis. • High-magnification EM provides accurate membrane segmentation and vesicle detection. [ABSTRACT FROM AUTHOR]

Abstract: Several lines of evidence demonstrate that glutamatergic system plays an important role in drug addiction. The present study was designed to investigate the effects of Chicago sky blue 6B (CSB6B), a vesicular glutamate transporters (VGLUTs) inhibitor, on methamphetamine (METH)-induced behaviors in mice. Mice were induced behavioral sensitization to METH by subcutaneous injection of 1mg/kg METH once daily for 7 days and then challenged with 1mg/kg METH in 14th day. Intracerebroventricular administration of CSB6B (7.5μg) 2.5h prior to METH was to observe its effects on METH -induced behavioral sensitization. Our results showed that the expressions of behavioral sensitization were significantly attenuated by intracerebroventricular administration of CSB6B 2.5h prior to METH either during the development period or before methamphetamine challenge in mice, while CSB6B itself had no effect on locomotor activity. Meanwhile, pretreatment of CSB6B also attenuated hyperactivity caused by a single injection of METH in mice. These results demonstrated that CSB6B, a VGLUTs inhibitor, attenuated acute METH-induced hyperactivity and chronic METH-induced behavioral sensitization, which indicated that VGLUTs were involved in the effect of chronic METH-induced behavioral sensitization and may be a new target against the addiction of METH. [Copyright &y& Elsevier]

Abstract: Andrographolides, a type of diterpene lactone, are widely known to have anti-inflammatory and anti-oxidative properties. CHP1002, a synthetic derivative of andrographolide, has similar anti-inflammatory action in mouse ear swelling test and rat paw edema test. In the present study, the mechanism of anti-inflammatory effects of CHP1002 was investigated in RAW264.7 macrophages. CHP1002 potently suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CHP1002 reduced the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 (PGE2). CHP1002 induced heme oxygenase-1 (HO-1) expression via activation of extracellular signal-regulated kinase (ERK) and NF-E2 related factor 2 transcription factor (Nrf2). Down-regulation of LPS-induced iNOS and COX-2 expressions was partially reversed by the HO-1 inhibitor zinc protoporphyrin (ZnPP). In addition, CHP1002 significantly attenuated LPS-induced TNF-α, IL-1β and IL-6 production. CHP1002 effectively induced HO-1 and was capable of inhibiting some macrophage-derived pro-inflammatory mediators, which may be closely correlated with its anti-inflammatory action. [Copyright &y& Elsevier]

• The roles of Ca2+/Mg2+ in PHACUF induced NF fouling were deeply studied. • Hydrophobic in appearance for PHACUF with a higher charge density than HA. • Mg2+ was more effective than Ca2+ in intensifying PHACUF size and NF fouling. • O 1s bonding energy shift and ITC data also provided powerful evidences. This study was conducted to systematically investigate how Ca2+/Mg2+ interacted with the preserved humic acid components after UF filtration (PHACUF) to cause fouling of nanofiltration (NF) membrane. Inherent characteristics including molecular weight distribution, charge, wettability, hydrodynamic size of PHACUF and its fractions under predetermined conditions and differences in PHACUF-induced NF membrane fouling behaviors, surface characteristics in the absence/presence of Ca2+/Mg2+ were analysed and explored, respectively. Microinteraction forces between PHACUF and Ca2+/Mg2+ were also compared. The results manifested that contrary to many typical reports about HA foulant, Mg2+ exhibited superior charge screening effect with PHACUF, and performance in accelerating hydrodynamic colloid size, dense membrane fouling compared to Ca2+. O 1s bonding energy shift and ITC data provided powerful and quantified evidences that Mg2+ could coordinate with PHACUF more effectively and cause more serious fouling deposits on NF membrane surfaces than Ca2+, presumably due to its favorable specific charge and binding ability. In terms of its own components, HOA fraction seems destined to preferentially bond with most of Ca2+ and Mg2+ ions and constitute a high proportion of membrane fouling loading because it possesses the highest charge density and content compared with other fractions in near-actual natural surface water circumstance. [ABSTRACT FROM AUTHOR]