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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.