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This is an article in the field of mineral materials. The utilization of desulfurized gypsum (FGD) to prepare more widely used hemihydrate gypsum plays a very important role in the resource utilization of industrial by-product gypsum. It can not only avoid the large-scale exploitation of natural gypsum, but also realize the resource utilization of desulfurized gypsum. In the process of converting FGD gypsum into hemihydrate gypsum, appropriate concentration of additive and sodium chloride were used as the reaction solution, and the process was heated and stirred under normal pressure. The effects of sodium chloride concentration, additive concentration, solid-liquid ratio, rotation speed and reaction temperature on the phase conversion time and crystal size of dihydrate to hemihydrate gypsum were studied. The increase of additive and sodium chloride concentration not only sped up the phase conversion process but also had a certain inhibitory effect on the average length and average aspect ratio of hemihydrate gypsum crystals. Higher or lower rotation speed hindered the nucleation and growth of hemihydrate gypsum crystals and affected the collision frequency of Ca2+ and SO42- in the NaCl added solution, thus delaying the formation of hemihydrate gypsum. Decreasing the solid-liquid ratio and increasing the temperature had a certain promoting effect on the phase conversion process. At a lower temperature, due to the insufficient driving force of the phase conversion process, it was difficult to transform FGD gypsum into hemihydrate gypsum. The optimal process conditions for preparing hemihydrate gypsum from FGD gypsum were determined as follows: sodium chloride concentration 10%, additive concentration 10%, solid-liquid ratio 1∶5, rotating speed 300 r/min, reaction temperature 100 ℃. Under the best process conditions, the reaction could be completed in 60 min. The average length of the prepared hemihydrate gypsum crystals was as high as 127 μm, and the average aspect ratio was as high as 19. At the same time, the relationship between the activity of water molecules in the solution, the degree of supersaturation and the reaction temperature was studied, and it was determined that the phase conversion process was determined by the temperature and the degree of supersaturation.

To reveal the role of gut microbiota (GM) in the occurrence and development of idiopathic central precocious puberty (ICPP) using 16S rDNA sequencing and bioinformatics analysis. The Danazol-induced ICPP model was successfully constructed in this study. ZBDH and GnRHa treatments could effectively inhibit ICPP in rats, as manifested by the delayed vaginal opening time, reduced weight, decreased uterine organ coefficient, and decreased uterine wall thickness and corpus luteum number, as well as remarkably reduced serum hormone (LH, FSH, and E2) levels. According to 16S rDNA sequencing analysis results, there was no significant difference in the GM community diversity across different groups; however, the composition of the microbial community and the abundance of the dominant microbial community were dramatically different among groups. ZBDH and GnRHa treatments could effectively reduce the abundance of Muribaculateae and Lactobacillus and promote Prevotella abundance. ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats.

Abstract Background To explore the application value of free omental wrapping and modified pancreaticojejunostomy in pancreaticoduodenectomy (PD). Methods The clinical data of 175 patients who underwent pancreaticoduodenectomy from January 2015 to December 2020 were retrospectively analysed. In total, 86 cases were divided into Group A (omental wrapping and modified pancreaticojejunostomy) and 89 cases were divided into Group B (control group). The incidences of postoperative pancreatic fistula and other complications were compared between the two groups, and univariate and multivariate logistic regression analyses were used to determine the potential risk factors for postoperative pancreatic fistula. Risk factors associated with postoperative overall survival were identified using Cox regression. Results The incidences of grade B/C pancreatic fistula, bile leakage, delayed bleeding, and reoperation in Group A were lower than those in Group B, and the differences were statistically significant (P

Dynamic microtubules play a critical role in cell structure and function. In nervous system, microtubules are the major route for cargo protein trafficking and they specially extend into and out of synapses to regulate synaptic development and plasticity. However, the detailed depolymerization mechanism that regulates dynamic microtubules in synapses and dendrites is still unclear. In this study, we find that KIF2C, a dynamic microtubule depolymerization protein without known function in the nervous system, plays a pivotal role in the structural and functional plasticity of synapses and regulates cognitive function in mice. Through its microtubule depolymerization capability, KIF2C regulates microtubule dynamics in dendrites, and regulates microtubule invasion of spines in neurons in a neuronal activity-dependent manner. Using RNAi knockdown and conditional knockout approaches, we showed that KIF2C regulates spine morphology and synaptic membrane expression of AMPA receptors. Moreover, KIF2C deficiency leads to impaired excitatory transmission, long-term potentiation, and altered cognitive behaviors in mice. Collectively, our study explores a novel function of KIF2C in the nervous system and provides an important regulatory mechanism on how activity-dependent microtubule dynamic regulates synaptic plasticity and cognition behaviors.

Abstract Background Wide applications of nanoparticles (NPs) have raised increasing concerns about safety to humans. Oxidative stress and inflammation are extensively investigated as mechanisms for NPs-induced toxicity. Autophagy and lysosomal dysfunction are emerging molecular mechanisms. Inhalation is one of the main pathways of exposing humans to NPs, which has been reported to induce severe pulmonary inflammation. However, the underlying mechanisms and, more specifically, the interplays of above-mentioned mechanisms in NPs-induced pulmonary inflammation are still largely obscure. Considered that NPs exposure in modern society is often unavoidable, it is highly desirable to develop effective strategies that could help to prevent nanomaterials-induced pulmonary inflammation. Results Pulmonary inflammation induced by intratracheal instillation of silica nanoparticles (SiNPs) in C57BL/6 mice was prevented by PJ34, a poly (ADP-ribose) polymerase (PARP) inhibitor. In human lung bronchial epithelial (BEAS-2B) cells, exposure to SiNPs reduced cell viability, and induced ROS generation, impairment in lysosome function and autophagic flux. Inhibition of ROS generation, PARP and TRPM2 channel suppressed SiNPs-induced lysosome impairment and autophagy dysfunction and consequent inflammatory responses. Consistently, SiNPs-induced pulmonary inflammation was prevented in TRPM2 deficient mice. Conclusion The ROS/PARP/TRPM2 signaling is critical in SiNPs-induced pulmonary inflammation, providing novel mechanistic insights into NPs-induced lung injury. Our study identifies TRPM2 channel as a new target for the development of preventive and therapeutic strategies to mitigate nanomaterials-induced lung inflammation. Graphical abstract

Conducting polymers are promising materials for diverse applications but the fabrication of conducting polymers mostly relies on conventional fabrication techniques. Here the authors introduce a high performance 3D printable conducting polymer ink to take full advantage of advanced 3D printing.

Summary: Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca2+, warm temperature, and oxidative stress. It is critically involved in physiological and pathological processes ranging from inflammation to stroke to neurodegeneration. At present, the channel’s gating and ion permeation mechanisms, such as the location and identity of the selectivity filter, remain ambiguous. Here, we report the cryo-electron microscopy (cryo-EM) structure of human TRPM2 in nanodisc in the ligand-free state. Cryo-EM map-guided computational modeling and patch-clamp recording further identify a quadruple-residue motif as the ion selectivity filter, which adopts a restrictive conformation in the closed state and acts as a gate, profoundly contrasting with its widely open conformation in the Nematostella vectensis TRPM2. Our study reveals the gating of human TRPM2 by the filter and demonstrates the feasibility of using cryo-EM in conjunction with computational modeling and functional studies to garner structural information for intrinsically dynamic but functionally important domains.

Prevailing alternative technologies of vanadium extraction from vanadium slag that suffer from high production costs, energy consumption and serious environmental pollution due to the large production of toxic solid-liquid-gaseous effluents are that non-environmental-friendly. This study implemented a new, cleaner, more effective and environmentally-friendly method of the single cyclic roasting-acid leaching, where vanadium clinker, residue and liquor can be recycled as roasting additive and leaching agent to enhance the roasting-leaching effect. The complete single cyclic roasting-acid leaching process of the chemicals, mechanisms and the maximum roasting conversion efficiency achieved in the case of vanadium is 88.86%–92.39% and leaching efficiency of 93.77%–97.61%. Herein, the recycling and reuse of all the liquor and leaching residue result in the zero-liquid discharge, solid waste reduction, significant cleanliness, and high resource utilization. This work has opened a new pathway of establishing a significantly cleaner production process for environmental sustainability via design and incorporation of inner recycling of wastes into the process in which these wastes are produced. In addition, the thermodynamics and kinetics of the whole single cyclic roasting-acid leaching process analysis can help us understand the mechanisms. All results and conclusions have guiding significance to industrial production of V2O5 from vanadium slag.

Summary: Drugs targeting N-methyl-D-aspartate receptors (NMDARs) have been approved to treat major depressive disorder (MDD); however, the presence of undesirable psychotomimetic and cognitive side effects may limit their utility. In this study, we show that the phosphorylation levels of the GluN2B subunit at tyrosine (Y) 1070 increase in mice after both acute and chronic restraint stress (CRS) exposure. Preventing GluN2B-Y1070 phosphorylation via Y1070F mutation knockin produces effects similar to those of antidepressants but does not affect cognitive or anxiety-related behaviors in subject mice. Mechanistically, the Y1070F mutation selectively reduces non-synaptic NMDAR currents and increases the number of excitatory synapses in the layer 5 pyramidal neurons of medial prefrontal cortex (mPFC) but not in the hippocampus. Altogether, our study identifies phosphorylation levels of GluN2B-Y1070 in the mPFC as a dynamic, master switch guarding depressive behaviors, suggesting that disrupting the Y1070 phosphorylation of GluN2B subunit has the potential for developing new antidepressants.

Abstract Background Suicide has been one of the leading causes of deaths in the United States. One major cause of suicide is psychiatric stressors. The detection of psychiatric stressors in an at risk population will facilitate the early prevention of suicidal behaviors and suicide. In recent years, the widespread popularity and real-time information sharing flow of social media allow potential early intervention in a large-scale population. However, few automated approaches have been proposed to extract psychiatric stressors from Twitter. The goal of this study was to investigate techniques for recognizing suicide related psychiatric stressors from Twitter using deep learning based methods and transfer learning strategy which leverages an existing annotation dataset from clinical text. Methods First, a dataset of suicide-related tweets was collected from Twitter streaming data with a multiple-step pipeline including keyword-based retrieving, filtering and further refining using an automated binary classifier. Specifically, a convolutional neural networks (CNN) based algorithm was used to build the binary classifier. Next, psychiatric stressors were annotated in the suicide-related tweets. The stressor recognition problem is conceptualized as a typical named entity recognition (NER) task and tackled using recurrent neural networks (RNN) based methods. Moreover, to reduce the annotation cost and improve the performance, transfer learning strategy was adopted by leveraging existing annotation from clinical text. Results & conclusions To our best knowledge, this is the first effort to extract psychiatric stressors from Twitter data using deep learning based approaches. Comparison to traditional machine learning algorithms shows the superiority of deep learning based approaches. CNN is leading the performance at identifying suicide-related tweets with a precision of 78% and an F-1 measure of 83%, outperforming Support Vector Machine (SVM), Extra Trees (ET), etc. RNN based psychiatric stressors recognition obtains the best F-1 measure of 53.25% by exact match and 67.94% by inexact match, outperforming Conditional Random Fields (CRF). Moreover, transfer learning from clinical notes for the Twitter corpus outperforms the training with Twitter corpus only with an F-1 measure of 54.9% by exact match. The results indicate the advantages of deep learning based methods for the automated stressors recognition from social media.

Rab3-interacting molecules (RIMs) are a key component of the presynaptic active zone that regulate neurotransmitter release. Here, the authors show that RIM1 also has postsynaptic function to organize NMDA receptors and synaptic response.

As an oxidative stress sensor, transient receptor potential melastatin 2 (TRPM2) channel is involved in many physiological and pathological processes including warmth sensing, ischemia injury, inflammatory diseases and diabetes. Intracellular calcium is critical for TRPM2 channel activation and the IQ-like motif in the N-terminus has been shown to be important by mediating calmodulin binding. Sequence analysis predicted two potential EF-loops in the N-terminus of TRPM2. Site-directed mutagenesis combining with functional assay showed that substitution with alanine of several residues, most of which are conserved in the typical EF-loop, including D267, D278, D288, and E298 dramatically reduced TRPM2 channel currents. By further changing the charges or side chain length of these conserved residues, our results indicate that the negative charge of D267 and the side chain length of D278 are critical for calcium-induced TRPM2 channel activation. G272I mutation also dramatically reduced the channel currents, suggesting that this site is critical for calcium-induced TRPM2 channel activation. Furthermore, D267A mutant dramatically reduced the currents induced by calcium alone compared with that by ADPR, indicating that D267 residue in D267–D278 motif is the most important site for calcium sensitivity of TRPM2. In addition, inside-out recordings showed that mutations at D267, G272, D278, and E298 had no effect on single-channel conductance. Taken together, our data indicate that D267–D278 motif in the N-terminus as a novel EF-loop is critical for calcium-induced TRPM2 channel activation.

To improve the borehole sealing effect of coal seam water infusion, especially that of coal seam with low permeability and high rigidity, this study investigated the performance test optimization of two cement-based sealing materials. The borehole sealing effect of this coal seam requires high-pressure water infusion. Result shows that when the water-cement ratio is 0.4 and the amount of fiber expansive agent is 10%, the new borehole sealing material displays microexpansion. In addition, the 1-day compressive strength reaches 16 MPa. This result satisfies the material compressive strength requirement under 30 MPa high-pressure water infusion. The sealing performance is also excellent. According to the scanning electron microscopy analysis of new borehole and traditional borehole sealing materials, the surface of new borehole sealing material shows no holes and possesses compactness. The sealing effect is superior to that of other traditional sealing materials. This effect can satisfy the sealing requirement of coal seam water infusion. The new borehole sealing material is considerably significant for the improvement of the water infusion effect.

Huntingtin-interacting protein 1-related (HIP1R) protein is considered to be an endocytic adaptor protein like the other two members of the Sla2 family, Sla2p and HIP1. They all contain homology domains responsible for the binding of clathrin, inositol lipids and F-actin. Previous studies have revealed that HIP1R is highly expressed in different regions of the mouse brain and localizes at synaptic structures. However, the function of HIP1R in the nervous system remains unknown. In this study, we investigated HIP1R function in cultured rat hippocampal neurons using an shRNA knockdown approach. We found that, after HIP1R knockdown, the dynamics and density of dendritic filopodia, and dendritic branching and complexity were significantly reduced in developing neurons, as well as the densities of dendritic spines and PSD95 clusters in mature neurons. Moreover, HIP1R deficiency led to significantly reduced expression of the ionotropic glutamate receptor GluA1, GluN2A and GluN2B subunits, but not the GABAA receptor α1 subunit. Similarly, HIP1R knockdown reduced the amplitude and frequency of the miniature excitatory postsynaptic current, but not of the miniature inhibitory postsynaptic current. In addition, the C-terminal proline-rich region of HIP1R responsible for cortactin binding was found to confer a dominant-negative effect on dendritic branching in cultured developing neurons, implying a critical role of cortactin binding in HIP1R function. Taken together, the results of our study suggest that HIP1R plays important roles in dendritic development and excitatory synapse formation and function.

Cu2+ is an essential metal ion that plays a critical role in the regulation of a number of ion channels and receptors in addition to acting as a cofactor in a variety of enzymes. Here, we showed that human melastatin transient receptor potential 2 (hTRPM2) channel is sensitive to inhibition by extracellular Cu2+. Cu2+ at concentrations as low as 3 µM inhibited the hTRPM2 channel completely and irreversibly upon washing or using Cu2+ chelators, suggesting channel inactivation. The Cu2+-induced inactivation was similar when the channels conducted inward or outward currents, indicating the permeating ions had little effect on Cu2+-induced inactivation. Furthermore, Cu2+ had no effect on singe channel conductance. Alanine substitution by site-directed mutagenesis of His995 in the pore-forming region strongly attenuated Cu2+-induced channel inactivation, and mutation of several other pore residues to alanine altered the kinetics of channel inactivation by Cu2+. In addition, while introduction of the P1018L mutation is known to result in channel inactivation, exposure to Cu2+ accelerated the inactivation of this mutant channel. In contrast with the hTRPM2, the mouse TRPM2 (mTRPM2) channel, which contains glutamine at the position equivalent to His995, was insensitive to Cu2+. Replacement of His995 with glutamine in the hTRPM2 conferred loss of Cu2+-induced channel inactivation. Taken together, these results suggest that Cu2+ inactivates the hTRPM2 channel by interacting with the outer pore region. Our results also indicate that the amino acid residue difference in this region gives rise to species-dependent effect by Cu2+ on the human and mouse TRPM2 channels.

The central nervous system (CNS) insults may cause massive demyelination and lead to the release of myelin-associated proteins including its major component myelin basic protein (MBP). MBP is reported to induce glial activation but its effect on neurons is still little known. Here we found that MBP specifically bound to the extracellular surface of the neuronal plasma membrane and induced neurotoxicity in vitro. This effect of MBP on neurons was basicity-dependent because the binding was blocked by acidic lipids and competed by other basic proteins. Further studies revealed that MBP induced damage to neuronal membrane integrity and function by depolarizing the resting membrane potential, increasing the permeability to cations and other molecules, and decreasing the membrane fluidity. At last, artificial liposome vesicle assay showed that MBP directly disturbed acidic lipid bilayer and resulted in increased membrane permeability. These results revealed that MBP induces neurotoxicity through its direct interaction with acidic components on the extracellular surface of neuronal membrane, which may suggest a possible contribution of MBP to the pathogenesis in the CNS disorders with myelin damage.

Inflammatory response following central nervous system (CNS) injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI), i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3)-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-kappaB signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-kappaB activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin) and myelin basic protein (MBP, one of the major proteins of myelin) are not able to activate NF-kappaB signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI.

Scandium, as a typical dispersed element, plays an important role in modern technology. The liquid-liquid microextraction of scandium from an aqueous solution is carried out with C16H35O3P (EHEHPA) as the extraction agent with kerosene as the diluent. The effects of pH of an aqueous solution, outer-inner rotor distance (D), the height of inner rotor (H), speed of the inner rotor (R), the flow velocity of the organic phase (QO), and the ratio of organic phase to the aqueous phase (O/A) on extraction efficiency, mass transfer coefficient and equilibrium mechanism of Sc3+ are analyzed investigated. The results of this study revealed that the removal rate of Sc3+ in the aqueous phase reaches more than 97%. To investigate the influence of NaOH concentration on the extraction process, NaOH solution is selected as a stripping agent for reverse extraction of the loaded organic phase. [ABSTRACT FROM AUTHOR]

Herein, fluosilicic acid, a by-product generated from the wet process of phosphoric acid, is successfully used to synthesize silica substrate. Then three novel adsorbents calcium silicate hydrates (CSH), Al modified CSH (Al-CSH) and F modified CSH (F-CSH) are synthesized from this silica substrate and used as adsorbents to remove Cr(III). Consequently, the largest surface area and abundant pore structure render Al-CSH the best performance for Cr(III) removal. The combination of characterization (X-ray diffraction, Brunauer–Emmett–Teller, scanning electron microscopy, X-ray photoelectron spectroscopy, and UV–Vis] and kinetic experiments reveal the adsorption of Al-CSH proceeds through an ion-exchange mechanism, which follows pseudo-second-order kinetics and Langmuir adsorption model. Moreover, the obtained Cr-bearing Al-CSH could be converted into an efficient photocatalyst by annealing at 300°C/Air, which shows excellent degradation efficiency of 94% for methylene blue during five cycles. This work proposes a route “waste → adsorbent → catalyst”, which is significant for waste utilization and water purification. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage caused by a ruptured intracranial aneurysm (RIA) is a devastating condition with significant morbidity and mortality. Despite the fact that RIAs can be prevented by microsurgical clipping or endovascular coiling, there are no reliable means of effectively predicting IA patients at risk for rupture. The purpose of our study was to discover differentially-expressed glycoproteins in IAs with or without rupture as potential biomarkers to predict rupture. Methods: Forty age/gender-matched patients with RIA, unruptured IA (UIA), healthy controls (HCs) and disease controls (DCs) (discovery cohort, n = 10 per group) were recruited and a multiplex quantitative proteomic method, iTRAQ (isobaric Tagging for Relative and Absolute protein Quantification), was used to quantify relative changes in the lectin-purified glycoproteins in CSF from RIAs and UIAs compared to HCs and DCs. Then we verified the proteomic results in an independent set of samples (validation cohort, n = 20 per group) by enzyme-linked immunosorbent assay. Finally, we evaluated the specificity and sensitivity of the candidate marker with receiver operating characteristic (ROC) curve methods. Results: The proteomic findings identified 294 proteins, 40 of which displayed quantitative changes unique to RIA, 13 to UIA, and 20 to IA. One of these proteins, receptor tyrosine kinase Axl, was significantly increased in RIA, as confirmed in CSF from the discovery cohort as well as in CSF and plasma from the validation cohort (p <0.05). Spearman's correlation analysis revealed that the CSF and plasma Axl levels were strongly correlated (r = 0.93, p <0.0001). The ROC curve indicated an optimal CSF Axl threshold of 0.12 nM for discriminating RIA from UIA with corresponding sensitivity/specificity of 73.33%/90% and an area under the curve (AUC) of 0.89 (95% CI: 0.80-0.97, p < 0.0001). The optimal threshold for plasma Axl was 1.7 nM with corresponding sensitivity/ specificity of 50%/80% and an AUC of 0.71 (95% CI: 0.54-0.87, p = 0.027). Conclusions: Both CSF and plasma Axl levels are significantly elevated in RIA patients. Axl might serve as a promising biomarker to predict the rupture of IA. [ABSTRACT FROM AUTHOR]

Long-term potentiation of glutamatergic transmission has been observed after physiological learning or pathological injuries in different brain regions, including the spinal cord, hippocampus, amygdala, and cortices. The insular cortex is a key cortical region that plays important roles in aversive learning and neuropathic pain. However, little is known about whether excitatory transmission in the insular cortex undergoes plastic changes after peripheral nerve injury. Here, we found that peripheral nerve ligation triggered the enhancement of AMPA receptor (AMPAR)-mediated excitatory synaptic transmission in the insular cortex. The synaptic GluA1 subunit of AMPAR, but not the GluA2/3 subunit, was increased after nerve ligation. Genetic knock-in mice lacking phosphorylation of the Ser845 site, but not that of the Ser831 site, blocked the enhancement of the synaptic GluA1 subunit, indicating that GluA1 phosphorylation at the Ser845 site by protein kinase A (PKA) was critical for this upregulation after nerve injury. Furthermore, A-kinase anchoring protein 79/150 (AKAP79/ 150) and PKA were translocated to the synapses after nerve injury. Genetic deletion of adenylyl cyclase subtype 1 (AC1) prevented the translocation of AKAP79/150 and PKA, as well as the upregulation of synaptic GluA1-containing AMPARs. Pharmacological inhibition of calcium-permeable AMPAR function in the insular cortex reduced behavioral sensitization caused by nerve injury. Our results suggest that the expression of AMPARs is enhanced in the insular cortex after nerve injury by a pathway involving AC1, AKAP79/150, and PKA, and such enhancement may at least in part contribute to behavioral sensitization together with other cortical regions, such as the anterior cingulate and the prefrontal cortices. [ABSTRACT FROM AUTHOR]

Inflammatory response following central nervous system (CNS) injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI), i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3)-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-κB signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-κB activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin) and myelin basic protein (MBP, one of the major proteins of myelin) are not able to activate NF-κB signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI. [ABSTRACT FROM AUTHOR]

The predispersed solvent extraction (PDSE) is a new method for separating solutes from aqueous solution, and for its high extraction ratio, the PDSE presents huge potential for the extraction from dilute solution. In the present paper, colloidal liquid aphrons are successfully generated using kerosene as a solvent, di(2-ethylhexyl)phosphoric acid (D2EHPA) as an extractant, sodium dodecyl benzene sulfate (SDBS) as surfactant in the aqueous phase, and polyoxyethylene sorbitol anhydride monolaurate (Tween-20) in oil phase. The extraction of Mg2+from ammonium dihydrogen phosphate solution is studied by using colloidal liquid aphrons (CLA) and colloidal gas aphrons (CGA) in a semibatch extraction column. To study the extraction ratio and advantages of the PDSE process in the removal of Mg2+, various parameters, initial Mg2+concentration, D2EHPA volume fraction, reaction temperature, phase volume ratio, mass fractions of dodecyl trimethylammonium bromide (HTAB), mass fractions of SDBS, mass fractions of Tween-20, and initial pH of NH4H2PO4solution, are studied and optimized. The results show that Mg2+in NH4H2PO4solution can be effectively removed by the PDSE process. An extraction ratio of more than 86.3% is attained at the optimized parameters, and superior-grade NH4H2PO4(MAP) can be obtained by two levels of extraction. [ABSTRACT FROM AUTHOR]

Using histamine and the H3 receptor antagonist thioperamide, the roles of histamine receptors in NMDA-induced necrosis were investigated in rat cultured cortical neurons. Within 3 h of intense NMDA insult, most neurons died by necrosis. Histamine reversed the neurotoxicity in a concentration-dependent manner and showed peak protection at a concentration of 10−7 m. This protection was antagonized by the H2 receptor antagonists cimetidine and zolantidine but not by the H1 receptor antagonists pyrilamine and diphenhydramine. In addition, the selective H2 receptor agonist amthamine mimicked the protection by histamine. This action was prevented by cimetidine but not by pyrilamine. 8-Bromo-cAMP also mimicked the effect of histamine. In contrast, both the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine and the cAMP-dependent protein kinase inhibitor N-[2-( p-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide reversed the protection by histamine. Thioperamide also attenuated NMDA-induced excitotoxicity, which was reversed by the H3 receptor agonist (R)-α-methylhistamine but not by pyrilamine and cimetidine. In addition, the protection by thioperamide was inhibited by the GABAA receptor antagonists picrotoxin and bicuculline. Further study demonstrated that the protection by thioperamide was due to increased GABA release in NMDA-stimulated samples. These results indicate that not only the H2 receptor/cAMP/cAMP-dependent protein kinase pathway but also the H3 receptor/GABA release pathway can attenuate NMDA-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of oxygen–glucose deprivation (OGD) on degranulation and histamine release of mast cells. Cultured mast cells were exposed to OGD for 1, 2, 4, 8, or 16 h. At 2 h of OGD exposure, the degranulation percentage of mast cells had increased and subsequently showed a progressive further increase, associated with a similar change in lactate dehydrogenase release. Histamine release increased significantly from 1 h of OGD exposure. These results indicate that OGD induces mast cells to degranulate, possibly via a cytotoxic response. This in vitro ischemic model of mast cells might clarify their roles in the pathological processes induced by cerebral ischemia. [ABSTRACT FROM AUTHOR]

This work introduced a novel microchannel extractor. The extraction system was intended to extract lanthanum nitrate aqueous solution with 2-ethylhexyl phosphoric acid-2-ethylhexyl ester (EHEHPA). Different feeding methods and inner rotors were explored first. The results showed that parallel feeding and inner rotors engraved with spiral stripes were more favorable for extraction. Next, the effect of various factors on the extraction was explored, including the aqueous phase pH, rotational inner rotor speed (R) and the fluid volumetric flow rate (Q). The results showed that these factors are closely related to the extraction. Finally, the experiment was verified by CFD numerical simulation, the simulation result was consistent with the experiment. In this device, active mixing was introduced into the microchannel extraction, which significantly improved the extraction efficiency. Under certain conditions, the extraction efficiency of this device exceeded stirring extraction equilibrium. Moreover, the extraction in the device is faster than with conventional stirring extraction. These advantages provide a possibility for highly efficient extraction of rare earth elements. [ABSTRACT FROM AUTHOR]

The article presents a study which showed that late endosomes promote actin-cytoskeleton remodeling through cytosolic translocation of immature protease cathepsin D (cathD) during microglia migration. Late endosomes are a type of prelysosomal organelles. Also cited are the identification of cathD as a key lysosomal molecule, and its role in the activity of actin-severing protein cofilin to maintain globular-actin (G-actin) monomers.

The crystallization of ammonium dihydrogen phosphate (MAP) is largely affected by certain metal ions such as Fe (III), and the influence seems to be pointed at both ends. Therefore, the industrial-grade MAP products can only be obtained by purifying the neutralized MAP solution from wet-process phosphoric acid (WPA). The extraction kinetics of Fe (III) from MAP solution using di-2-ethylhexyl phosphoric acid (D2EHPA) in sulfonated kerosene measured by the Lewis cell. The extraction mechanism is discussed and confirmed on the basis of the dimeric model of D2EHPA in non-polar solution. From the temperature dependence of reaction rate, the value of Ea and Kf are calculated and the extraction regimes are deduced to be mixed controlled with diffusion and chemical reaction for Fe (III). Ultimately, the rate equation for the extraction reaction of Fe (III) with D2EHPA is obtained as follows: Rf = 0.08cFe3+1.2cH2A2 0.81cH+-0.85. [ABSTRACT FROM AUTHOR]

Activation of the transient receptor potential melastatin 2 (TRPM2) channel occurs during the response to oxidative stress under physiological conditions as well as in pathological processes such as ischemia and diabetes. Accumulating evidence indicates that adenosine diphosphate ribose (ADPR) is the most important endogenous ligand of TRPM2. However, although it is known that ADPR binds to the NUDT9 homology (NUDT9-H) domain in the intracellular C-terminal region, the molecular mechanism underlying ADPR binding and activation of TRPM2 remains unknown. In this study, we generate a structural model of the NUDT9-H domain and identify the binding pocket for ADPR using induced docking and molecular dynamics simulation. We find a subset of 11 residues--H1346, T1347, T1349, L1379, G1389, S1391, E1409, D1431, R1433, L1484, and H1488--that are most likely to directly interact with ADPR. Results from mutagenesis and electrophysiology approaches support the predicted binding mechanism, indicating that ADPR binds tightly to the NUDT9-H domain, and suggest that the most significant interactions are the van der Waals forces with S1391 and L1484, polar solvation interaction with E1409, and electronic interactions (including π-π interactions) with H1346, T1347, Y1349, D1431, and H1488. These findings not only clarify the roles of a range of newly identified residues involved in ADPR binding in the TRPM2 channel, but also reveal the binding pocket for ADPR in the NUDT9-H domain, which should facilitate structure-based drug design for the TRPM2 channel. [ABSTRACT FROM AUTHOR]

N-Methyl-D-aspartate receptor (NMDAR) synaptic incorporation changes the number of NMDARs at synapses and is thus critical to various NMDAR-dependent brain functions. To date, the molecules involved in NMDAR trafficking and the underlying mechanisms are poorly understood. Here, we report that myosin IIb is an essential molecule in NMDAR synaptic incorporation during PKC- or θ burst stimulation-induced synaptic plasticity. Moreover, we demonstrate that myosin light chain kinase (MLCK)-dependent actin reorganization contributes to NMDAR trafficking. The findings from additional mutual occlusion experiments demonstrate that PKC and MLCK share a common signaling pathway in NMDAR-mediated synaptic regulation. Because myosin IIb is the primary substrate of MLCK and can regulate actin dynamics during synaptic plasticity, we propose that the MLCK- and myosin IIb-dependent regulation of actin dynamics is required for NMDAR trafficking during synaptic plasticity. This study provides important insights into a mechanical framework for understanding NMDAR trafficking associated with synaptic plasticity. [ABSTRACT FROM AUTHOR]

The number and subunit composition of synaptic N-methyl- D-aspartate receptors (NMDARs) play critical roles in synaptic plasticity, learning, and memory and are implicated in neurological disorders. Tyrosine phosphorylation provides a powerful means of regulatingNMDARfunction, but the underling mechanism remains elusive. In this study we identified a tyrosine site on the GluN2B subunit, Tyr-1070, which was phosphorylated by a proto-oncogene tyrosine-protein (Fyn) kinase and critical for the surface expression of GluN2B-containing NMDARs. The phosphorylation of GluN2B at Tyr-1070 was required for binding of Fyn kinase to GluN2B, which up-regulated the phosphorylation of GluN2B at Tyr-1472. Moreover, our results revealed that the phosphorylation change of GluN2B at Tyr-1070 accompanied the Tyr-1472 phosphorylation and Fyn associated with GluN2B in synaptic plasticity induced by both chemical and contextual fear learning. Taken together, our findings provide a new mechanism for regulating the surface expression of NMDARs with implications for synaptic plasticity. [ABSTRACT FROM AUTHOR]

In this paper, the liquid-liquid equilibrium (LLE) and tie-line data of the system containing 1-butanol + water + tri-n-butyl phosphate (TBP) + ammonium chloride have been studied at 298.15, 308.15 and 318.15 K under atmospheric pressure. The influence of temperature and different concentrations of ammonium chloride have been investigated. In addition, nonrandom two-liquid (NRTL) model is applied to the system, and the relevant interaction parameters are regressed with the experimental data. The quality of the correlation is measured by the rmsd (rmsd≤0.0131). The results show that the calculated values by NRTL model are in agreement with the determination of LLE data of the studied system in the investigated conditions. [ABSTRACT FROM AUTHOR]

Zinc ion (Zn2+) is an endogenous allosteric modulator that regulates the activity of a wide variety of ion channels in a reversible and concentration-dependent fashion. Here we used patch clamp recording to study the effects of Zn2+ on the melastatin transient receptor potential 2 (TRPM2) channel. Zn2+ inhibited the human (h) TRPM2 channel currents, and the steady-state inhibition was largely not reversed upon washout and concentration-independent in the range of 30-1000 μm, suggesting that Zn2+ induces channel inactivation. Zn2+ inactivated the channels fully when they conducted inward currents, but only by half when they passed outward currents, indicating profound influence of the permeant ion on Zn2+ inactivation. Alanine substitution scanning mutagenesis of 20 Zn2+-interacting candidate residues in the outer pore region of the hTRPM2 channel showed that mutation of Lys952 in the extracellular end of the fifth transmembrane segment and Asp1002 in the large turret strongly attenuated or abolished Zn2+ inactivation, and mutation of several other residues dramatically changed the inactivation kinetics. The mouse (m) TRPM2 channels were also inactivated by Zn2+, but the kinetics were remarkably slower. Reciprocal mutation of His995 in the hTRPM2 channel and the equivalent Gln992 in the mTRPM2 channel completely swapped the kinetics, but no such opposing effects resulted from exchanging another pair of species-specific residues, Arg961/Ser958. We conclude from these results that Zn2+ inactivates the TRPM2 channels and that residues in the outer pore are critical determinants of the inactivation. [ABSTRACT FROM AUTHOR]

The cytoplasmic C-terminal domains of NR2 subunits have been proposed to modulate the assembly and trafficking of NMDA receptors. However, questions remain concerning which domains in the C terminus ofNR2 subunits control the assembly of receptor complexes and how the assembled complexes are selectively trafficked through the various cellular compartments such as endoplasmic reticulum (ER) to the cell surface. In the present study, we found that the three amino acid tail after the TM4 region ofNR2 subunits is necessary for surface expression of functional NMDA receptors, while truncations with only two amino acids following the TM4 region (NR2Δ2) completely eliminated surface expression of the NMDA receptor on co-expression with NR1-1a in HEK293 cells. FRET (fluorescence resonance energy transfer) analysis showed that these NR2Δ2 truncations are able to form homomers and heteromers on co-expression with NR1-1a. Furthermore, when NR2A2 subunits were cotransfected with either the NR1-4a or NR1-1aAAA mutant, lacking the ER retention motif (RRR), functional NMDA receptors were detected in the transfected HEK293 cells. Unexpectedly, we found that the replacement of five residues after TM4 with alanines gave results indistinguishable from those of NR2BΔ5 (EHLFY), demonstrating the short tail following the TM4 of NR2 subunits is not sequence-specific-dependent. Taken together, our results show that the C terminus of the NR2 subunits is not necessary for the assembly of NMDA receptor complexes, whereas a three amino acid long cytoplasmic tail following the TM4 of NR2 subunits is sufficient to overcome the ER retention existing in the C terminus of NR1, allowing the assembled NMDA receptors to reach the cell surface. [ABSTRACT FROM AUTHOR]