Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.

BACKGROUND: Olfactory dysfunction occurs frequently in Parkinson's disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. METHODS: MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R-) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. RESULTS: Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R- HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. CONCLUSIONS: This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Overexpression of OsACL5 triggers environmentally-dependent leaf rolling and reduces grain size in rice.

Major polyamines include putrescine, spermidine, spermine and thermospermine, which play vital roles in growth and adaptation against environmental changes in plants. Thermospermine (T-Spm) is synthetised by ACL5. The function of ACL5 in rice is still unknown. In this study, we used a reverse genetic strategy to investigate the biological function of OsACL5. We generated several knockout mutants by pYLCRISPR/Cas9 system and overexpressing (OE) lines of OsACL5. Interestingly, the OE plants exhibited environmentally-dependent leaf rolling, smaller grains, lighter 1000-grain weight and reduction in yield per plot. The area of metaxylem vessels of roots and leaves of OE plants were significantly smaller than those of WT, which possibly caused reduction in leaf water potential, resulting in leaf rolling with rise in the environmental temperature and light intensity and decrease in humidity. Additionally, the T-Spm contents were markedly increased by over ninefold whereas the ethylene evolution was reduced in OE plants, suggesting that T-Spm signalling pathway interacts with ethylene pathway to regulate multiple agronomic characters. Moreover, the osacl5 exhibited an increase in grain length, 1000-grain weight, and yield per plot. OsACL5 may affect grain size via mediating the expression of OsDEP1, OsGS3 and OsGW2. Furthermore, haplotypes analysis indicated that OsACL5 plays a conserved function on regulating T-Spm levels during the domestication of rice. Our data demonstrated that identification of OsACL5 provides a theoretical basis for understanding the physiological mechanism of T-Spm which may play roles in triggering environmentally dependent leaf rolling; OsACL5 will be an important gene resource for molecular breeding for higher yield.

Bioinformatics analysis of KLF2 as a potential prognostic factor in ccRCC and association with epithelial-mesenchymal transition.

Clear cell renal cell carcinoma (ccRCC) is a primary pathological subtype of RCC and has poor clinical outcome. Krüppel-like factors (KLFs), which are zinc-finger proteins, may be involved in ccRCC development and progression. KLFs belong to the zinc-finger family of DNA-binding transcription factors and regulate transcription of downstream target genes. KLFs are involved in cancer development. The present study aimed to investigate the role of KLFs in ccRCC prognosis. The Cancer Genome Atlas database and multifactorial analysis showed that KLFs were widely expressed in pan-cancers and KLF2 was an independent protective factor for ccRCC prognosis. Patients with low KLF2 expression had a low survival probability and expression of KLF2 was downregulated in patients with ccRCC with high pathological grade (II + III vs. I). In addition, western blot and reverse transcription-quantitative PCR revealed that KLF2 was expressed at low levels in ccRCC cell lines and overexpression of KLF2 inhibited cell migration. In addition, KLF2 expression was negatively correlated with methylation. KLF2 expression was elevated following treatment of ccRCC cells with DNA methyltransferase inhibitor. A prognostic risk index prediction model was constructed based on multiple Cox regression. The receiver operating characteristic curve was 0.780 (area under curve >0.5). Furthermore, Gene Ontology enrichment analysis showed that 'cell adhesion' and 'junction' were negatively correlated with KLF2 and that high-risk group exhibited significantly activated 'epithelial-mesenchymal transition'. Western blot analysis showed that overexpression of KLF2 increased expression of E-cadherin, while decreasing levels of N-cadherin and vimentin. The present study highlighted the role of KLFs in ccRCC prognosis prediction and provides a research base for the search of validated prognostic biological markers for ccRCC.

eIF4E1 Regulates Arabidopsis Embryo Development and Root Growth by Interacting With RopGEF7.

Eukaryotic translation initiation factor 4E1 (eIF4E1) is required for the initiation of protein synthesis. The biological function of eIF4E1 in plant-potyvirus interactions has been extensively studied. However, the role of eIF4E1 in Arabidopsis development remains unclear. In this study, we show that eIF4E1 is highly expressed in the embryo and root apical meristem. In addition, eIF4E1 expression is induced by auxin. eIF4E1 mutants show embryonic cell division defects and short primary roots, a result of reduced cell divisions. Furthermore, our results show that mutation in eIF4E1 severely reduces the accumulation of PIN-FORMED (PIN) proteins and decreases auxin-responsive gene expression at the root tip. Yeast two-hybrid assays identified that eIF4E1 interacts with an RAC/ROP GTPase activator, RopGEF7, which has been previously reported to be involved in the maintenance of the root apical meristem. The interaction between eIF4E1 and RopGEF7 is confirmed by protein pull-down and bimolecular fluorescent complementation assays in plant cells. Taken together, our results demonstrated that eIF4E1 is important for auxin-regulated embryo development and root growth. The eIF4E1-RopGEF7 interaction suggests that eIF4E1 may act through ROP signaling to regulate auxin transport, thus regulating auxin-dependent patterning.

Anesthetic Effect of Dexmedetomidine in Clinical Functional Neurosurgery.

Background: Dexmedetomidine is a highly selective and efficient α2-adrenoceptor agonist with good antianxiety, analgesic, hypnotic, and sedative effects without causing respiratory depression. Aim: To investigate the anesthetic effect of dexmedetomidine in clinical neurosurgery. Methods: A total of 94 patients who received functional neurosurgical treatment in our hospital from March 2019 to October 2020 were selected and divided into the study and control groups. Routine anesthesia was adopted in the control group, while dexmedetomidine was used in the study group. Perioperative hemodynamic indicators such as mean arterial pressure, heart rate, and peripheral capillary oxygen saturation, cognitive function score, pain score VAS, stress response index level, and incidence of adverse reactions were compared between the two groups. Results: Before surgery (T0), no significant differences in MAP, HR, and SpO2 were observed between the two groups. However, at the beginning of the operation (T1), 30 min after the operation (T2), and immediately after the operation (T3), these indicators in the study group were significantly higher than in the control group. The postoperative MMSE of the study group 3 d later was significantly higher than that of the control group. The VAS scores after the operation of the study group were lower than those of the control group. The serum cortisol (COR) and aldosterone (ALD) levels in the study group were not significantly different from those in the control group before surgery. The levels of each index in the two groups were higher than those before and 24 h after surgery. The incidence rate of adverse reactions in the study group was lower. Conclusion: The application of dexmedetomidine in clinical functional neurosurgery is safe and can maintain hemodynamic stability and reduce the degree of stress response, cognitive impairment, and pain caused by invasive surgery.

The Anesthetic Effect and Safety of Dexmedetomidine in Cesarean Section: A Meta-Analysis.

Objective: To evaluate the anesthetic effect and safety of dexmedetomidine in cesarean section. Methods: The Cochrane Library, EMBASE, and PubMed databases (established until September 2020) were searched by computer. Two authors independently screened and extracted literature related to the application of dexmedetomidine in the cesarean section according to inclusion and exclusion criteria. The control group received either subarachnoid block (lumbar anesthesia) or combined lumbar anesthesia and epidural anesthesia (combined lumbar epidural anesthesia) with bupivacaine or combined bupivacaine and fentanyl. The observation group was additionally given dexmedetomidine based on the control group, to analyze the anesthetic effect and safety of dexmedetomidine in cesarean section. Results: A total of 580 cesarean delivery women were included in 8 studies, and the results showed that the peak time of sensory block in the observation group was shorter than that in the control group (standard mean difference = -0.28; 95% confidence interval: -0.48, -0.08; P = 0.006), sensory block lasted longer than that in the control group (standard mean difference = 1.49; 95% confidence interval: 1.21, 1.78; P < 0.00001), the sedation rate was higher than that in the control group, the onset of the first postoperative pain was significantly delayed compared with that in the control group, and the incidence of postoperative pain, nausea and vomiting, postoperative chills, and fever was lower than that in the control group (P < 0.05). Conclusion: Dexmedetomidine combined with lumbar anesthesia or combined lumbar epidural anesthesia for women in cesarean section has more clinical benefits and better safety.

Influence of coracoglenoid space on scapular neck fracture stability: biomechanical study.

BACKGROUND: The anatomical variation of the coracoglenoid space has the potential to influence the stability of scapular neck fractures. This paper aimed to investigate the mechanical mechanism underlying the influence of different coracoglenoid space types on scapular neck fractures by morphometric analysis and biomechanical experiments. METHODS: The morphology of 68 dried scapulae (left: 36; right: 32) was studied. Two variables, the length of the coracoglenoid distance (CGD) and the coracoglenoid notch (CGN), were measured. The distribution of CGN/CGD × 100% was used to identify the morphology of the coracoglenoid space. Each specimen was tested for failure under static axial compression loading. The average failure load, stiffness, and energy were calculated. RESULTS: Two coracoglenoid space types were identified. The incidence of Type I (''hook'' shape) was 53%, and that of Type II (''square bracket'' shape) was 47%. The CGD and CGN were significantly higher for type I than type II (13.81 ± 0.74 mm vs. 11.50 ± 1.03 mm, P < 0.05; 4.74 ± 0.45 mm vs. 2.61 ± 0.45 mm, P < 0.05). The average maximum failure load of the two types was 1270.82 ± 318.85 N and 1529.18 ± 467.29 N, respectively (P = 0.011). The stiffness and energy were significantly higher for type II than type I (896.75 ± 281.14 N/mm vs. 692.91 ± 217.95 N/mm, P = 0.001; 2100.38 ± 649.54 N × mm vs. 1712.71 ± 626.02 N × mm, P = 0.015). CONCLUSIONS: There was great interindividual variation in the anatomical morphology of the coracoglenoid space. Type I (hook-like) spaces bore lower forces, were less stiff, and bore less energy, which may constitute an anatomical predisposition to scapular neck fractures.

Extracellular Matrix-Associated Pathways Promote the Progression of Gastric Cancer by Impacting the Dendritic Cell Axis.

BACKGROUND: Gastric cancer (GC) is the third most frequent malignant tumour in the Chinese population, let alone the whole world. Recently, most prognostic models have only focused on the levels of several genes, miRNAs, lncRNAs, gene mutations, or DNA methylation; however, the activation status of biological pathways is more stable and can reflect the comprehensive inner conditions of tumours. METHODS: We collected samples from the Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort and GSE62254 cohort, with a total of 594 patients. We employed GSEA to first compare the diverse activated signalling pathways between dead GC patients and living patients. The least absolute shrinkage and selection operator (LASSO) regression analysis was subsequently performed by the "glmnet" package to generate a prognostic signature. RESULTS: We extracted a total of 218 genes from the KEGG Focal Adhesion and KEGG ECM Receptor Interaction pathways, which showed significant activation in dead GC patients in two enrolled cohorts, for subsequent LASSO analysis. In the TCGA-STAD cohort, patients in the high-risk group faced a significantly poorer prognosis than those in the low-risk group (P < 0.001, HR: 4.62, 95% CI: 3.447-6.183), with an AUC of 0.694. In the GSE62254 cohort, the HR value was 4.94 (95% CI: 3.413-7.165), and the AUC value was as high as 0.834. A high-risk score and poor prognosis correlated with infiltrated dendritic cells, and the receptor of IFN-α was also positively linked with the risk score, as well as poor prognosis. GC patients with high-risk scores were more likely to respond to CTLA4 treatment but not PD1 treatment. CONCLUSION: Taken together, we established and verified an extracellular matrix prognostic model of gastric cancer patients. The model can be used to evaluate the risk of death of GC patients, as well as the response to anti-CTLA4 immunotherapy.

Maternal Nicotine Exposure Alters Hippocampal Microglia Polarization and Promotes Anti-inflammatory Signaling in Juvenile Offspring in Mice.

Accumulating evidence reveal that maternal smoking or perinatal nicotine replacement therapy impairs hippocampal neurogenesis, neural development, and cognitive behaviors in the offspring. Microglia is a source of non-neural regulation of neuronal development and postnatal neurogenesis. In this study, we explored the impact of nicotine on the microglia during the development of hippocampus. Developmental nicotine exposure in a mouse model was conducted by supplementing nicotine in the drinking water to mother mice during gestation and lactation period. We found that juvenile offspring with maternal nicotine exposure presented physical and neurobehavioral development delay and an increase in anxiety-like behavior in the open field test on postnatal day (PND) 20. To further detect possible developmental neurotoxic effects of nicotine in offspring and underlying mechanism, whole genome microarray analysis of the expression profile of the hippocampus was performed on postnatal day 20. Significant alterations in the expression of genes related to inflammatory, neurotransmitter, and synapsis were observed in the hippocampus after maternal nicotine exposure, as compared to the vehicle control. Concurrently, an increase in microglial markers and the presence of M2 polarity state in the hippocampus of the nicotine offspring were observed by histological analysis and confocal z-stacking scanning. The M2 microglial polarization state was further confirmed with in vitro primary microglia culture by cytokine array, and double-positive expression of BDNF/Iba1 in microglia by immunohistochemical staining in the juvenile offspring hippocampus was visualized. We also found that nicotine offspring showed an increase of neurite length in the molecular layer and CA1 by Tuj1 staining, as well as an increase in the expression of synapse associated protein, PSD95, but the expression of NeuroD1 in CA1 and CA3 reduced. In summary, maternal nicotine exposure dysregulates immune-related genes expression by skewing the polarity of M2 microglia in the hippocampus, which may cause abnormal cognitive and behavioral performance in the offspring.

Texture analysis based on U-Net neural network for intracranial hemorrhage identification predicts early enlargement.

BACKGROUND AND OBJECTIVE: Early hemorrhage enlargement in hypertensive cerebral hemorrhage indicates a poor prognosis. This study aims to predict the early enlargement of cerebral hemorrhage through the intelligent texture analysis of cerebral hemorrhage after segmentation. METHODS: A total of 54 patients with hypertensive intracerebral hemorrhage were selected and divided into enlarged hematoma (enlarged group) and non-enlarged hematoma (negative group). The U-Net Neural network model and contour recognition were used to extract the brain parenchymal region, and Mazda texture analysis software was used to extract regional features. The texture features were reduced by Fisher coefficient (Fisher), classification error probability combined average correlation coefficients (POE + ACC), and mutual information (MI) to select the best feature parameters. B11 module was used to analyze the selected features. The misclassified rate of feature parameters screened by different dimensionality reduction methods was calculated. RESULTS: The neural network based on U-Net can accurately identify the lesion of cerebral hemorrhage. Among the 54 patients, 18 were in the enlarged group and 36 in the negative group. The parameters of gray level co-occurrence matrix and gray level run length matrix can be used to predict the enlargement of intracerebral hemorrhage. Among the features screened by Fisher, POE + ACC and MI, the texture features of MI showed the lowest misclassified rate, which was 0. CONCLUSION: The texture analysis based on U-Net neural network is helpful to predict the early expansion of hypertensive cerebral hemorrhage, and the parameters of gray level co-occurrence matrix and gray level run length matrix under MI dimensionality reduction have the most excellent predictive value.

Blockade of 5-Hydroxytryptamine 2A Receptor Attenuates Precipitation of Naloxone-Induced Withdrawal Symptoms in Opioid-Exposed Mice.

Heroin dependency has become a global problem and has caused significant clinical and socioeconomic burdens along with devastating medical consequences. Chronic drug exposure alters the expression and functional activity of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) in the brain. Furthermore, pharmacological blockade of 5-HT2ARs reduces cue-induced cocaine craving behaviors. In this study, we explored the influence of 5-HT2ARs on heroin-withdrawal behaviors in mice. Black C57BL/6J mice were given gradually increasing (10-50 mg/kg over 4.5 days) doses of heroin to induce heroin dependency, after which naloxone was given to precipitate withdrawal symptoms. MDL100907, a selective and potent 5-HT2AR antagonist, attenuated naloxone-precipitated withdrawal symptoms in these mice. In addition, 5-HT2AR protein levels increased significantly in the medial prefrontal cortex (mPFC), while phosphorylation of extracellular signal-regulated kinase (p-ERK) decreased in the mPFC after heroin exposure. In conclusion, these results suggest that 5-HT2ARs might be involved in the development of opioid dependency and that pharmacological blocking of 5-HT2ARs might be a new therapeutic strategy for heroin dependency.

Increased risk of Ventriculostomy-Associated hemorrhage in patients treated with antiplatelet agents for stent-assisted coiling of ruptured intracranial aneurysms.

PURPOSE: The aim of this study is to evaluate the impact of antiplatelet agents for stent-assisted coiling, including intravenous (IV) tirofiban as an antiplatelet premedication, on rates of external ventricular drain (EVD)-related hemorrhage in acutely ruptured intracranial aneurysms. The impact of IV tirofiban in particular was also evaluated. METHODS: Rates of radiographically identified hemorrhage associated with EVD placement were compared between patients who received an antiplatelet agent for stent-assisted coil embolization (SACE), and patients who did not receive an antiplatelet agent between June 2013 and June 2019. RESULTS: 78 patients treated for a ruptured aneurysm which required an EVD were included. A total of 46 patients who underwent stent-assisted coiling and received IV tirofiban and oral asipirin and clopidogrel (DAPT) were included in the antiplatelet group, while 32 who underwent single coiling and received no antiplatelet therapy were included in the control group. Overall, EVD-related hemorrhage occurred in 13 patients (16.67%): 11 (23.91%) in the antiplatelet group and 2 (6.25%) in the control group (p = 0.040). Of 37 patients who underwent computed tomography after SACE, but before the use of DAPT, 8 (21.62%) exhibited EVD-related hemorrhage after IV tirofiban therapy (p = 0.070 vs. control group). EVD-related hemorrhage was not significantly different between patients with EVD placement after coil embolization versus before coil embolization (p = 0.124). In the subgroup analysis for the antiplatelet group, we did not observed increased EVD-related hemorrhage in patients receiving EVD placement after administration of antiplatelet agents (8/27 [29.63%]) versus before administration of antiplatelet agents (3/19 [15.79%]). CONCLUSION: Patients with ruptured aneurysm who receive an antiplatelet agent for stent-assisted coiling are at a higher risk for EVD-related hemorrhage. The order of EVD placement and EVT, as well as the order of EVD placement and antiplatelet initiation do not appear to be significantly different regarding the outcome of EVD-related hemorrhage.HighlightsPatients with ruptured aneurysm who receive an antiplatelet agent for stent-assisted coiling are at a higher risk for EVD-related hemorrhage.There was a trend towards higher EVD related haemorrhage when tirofiban was used but it did not reach statisitical significance.The order of EVD-whether before vs after endovascular treatment, or before vs after antiplatelet therapy did not influence the EVD-related hemorrhage rates.

Maternal Nicotine Exposure During Gestation and Lactation Period Affects Behavior and Hippocampal Neurogenesis in Mouse Offspring.

Cigarette smoking or nicotine exposure during pregnancy is associated with numerous obstetrical, fetal, and developmental complications, as well as an increased risk of adverse health consequences in the adult offspring. In this study, we examined the effects of maternal nicotine exposure during perinatal and lactation stages on behavioral performance and hippocampal neurogenesis in the adolescent stage of offspring mice. Female C57BL/mice received nicotine in drinking water (200 µg/ml nicotine) or vehicle (1% saccharin) starting from 2 weeks premating until the offspring were weaned on postnatal day 20. Experiments started on postnatal day 35. Female offspring with maternal nicotine exposure presented an increase in anxiety-like behavior in an open-field test. BrdU assay revealed that nicotine offspring presented an increase in cell proliferation in hippocampal dentate gyrus, but the number of BrdU+ cells was decreased in one week and further decreased in three weeks. The occurrence of disarray of DCX+ cells increased in both male and female nicotine offspring. The density of microglial marker protein Iba1 was significantly increased in the nicotine offspring. Furthermore, the expression of microglia marker Iba1, the CX3CL1, CX3CR1, and downstream molecules PKA and p-ErK were significantly increased in the nicotine group. In summary, maternal nicotine exposure affects both hippocampal neurogenesis and microglial activity in the adolescent offspring.

Construction of an experimental millerⅢ gingival retraction animal model in beagle dogs / 口腔疾病防治

Objective @#To construct a Miller class Ⅲ gingival recession animal model and to lay the foundation for exploring the treatment of Miller class Ⅲ gingival recession. @*Methods@#Two adult male beagle dogs were selected, and four teeth from each beagle dog were selected to establish an experimental Miller class Ⅲ gingival recession model. The root surface was revealed by removing the soft and hard tissues of the buccal side. The success of the model was determined by measuring the vertical gingival retraction (VGR), horizontal retraction (HGR), keratosis tissue width (KTW), gingival tissue thickness (GTT), and probing depth (PD) at 1, 2, 4, 6, and 8 weeks after modeling. @*Results@#After observing the clinical indexes, the PDs before and after the modeling were all smaller than 3 mm and no deep-period pockets were formed. The VGR before modeling was 0 mm, and the VGR range after modeling was 5-6.38 mm. A comparison of the before and after modeling results showed that this difference was statistically significant (P < 0.05). The postoperative VGR results were grouped according to timepoint. A comparison between the two groups showed that the differences at 2, 4, 6 and 8 weeks postoperatively were not statistically significant (P > 0.05). The HGR before the modeling was 0 mm, and the HGR fluctuated around 10.5 mm after the modeling, and this difference was statistically significant (P < 0.05). The HGR results were grouped by timepoint after surgery, and a one-way analysis of showed that the differences between the two groups were not statistically significant (P > 0.05). The KTW range before modeling was 6~9 mm, and it fluctuated around 2 mm after modeling, and this difference was statistically significant (P < 0.05). The KTW results were grouped by timepoint after surgery, and they indicated that significant differences did not occur between the groups postoperatively (P > 0.05). The pre-modeling GTT was 1.5 mm, and the GTT range after modeling was 1.5-2 mm. The preoperative and postoperative GTT results were grouped by timepoint, and the results showed that significant differences did not occur between 1 week and 2 weeks after surgery (P = 0.123), although a statistically significant difference was observed at 1 week postoperatively between this group and the other groups (P < 0.05).@*Conclusion@#The method used in this experiment can successfully build a Miller class III gingival recession animal model, and the model remains stable after wound healing.

Prussian Blue Analogue with Fast Kinetics Through Electronic Coupling for Sodium Ion Batteries.

Alternative battery systems based on the chemistry of sodium are being considered to offer sustainability and cost-effectiveness. Herein, a simple and new method is demonstrated to enable nickel hexacyanoferrate (NiHCF) Prussian blue analogues (PBA) nanocrystals to be an excellent host for sodium ion storage by functionalization with redox guest molecule. The method is achieved by using NiHCF PBA powders infiltrated with the 7,7,8,8-tetracyanoquinododimethane (TCNQ) solution. Experimental and ab initio calculations results suggest that TCNQ molecule bridging with Fe atoms in NiHCF Prussian blue analogue leads to electronic coupling between TCNQ molecules and NiHCF open-framework, which functions as an electrical highway for electron motion and conductivity enhancement. Combining the merits including high electronic conductivity, open framework structure, nanocrystal, and interconnected mesopores, the NiHCF/TCNQ shows high specific capacity, fast kinetics and good cycling stability, delivering a high specific capacity of 35 mAh g-1 after 2000 cycles, corresponding a capacity loss of 0.035% decay per cycle.

A two-step etching route to ultrathin carbon nanosheets for high performance electrical double layer capacitors.

Two-dimensional (2D) carbon materials have attracted intense research interest for electrical double layer capacitors (EDLCs) due to their high aspect ratio and large surface area. Herein, we propose an exfoliation-chlorination route for preparing ultrathin carbon nanosheets by using ternary layered carbide Ti3AlC2 as the precursor. Due to the large intersheet space of exfoliated layered carbide (MXene), the as-prepared carbon nanosheets exhibit a thickness of 3-4 nm and a large specific surface area of 1766 m(2) g(-1) with hierarchical porosity. These features significantly improve the ion-accessible surface area for charge storage and shorten the ion transport length in the thin dimension. As a result, the carbon nanosheets show a high specific capacitance (220 F g(-1) at 0.5 A g(-1)), remarkable high power capability (79% capacitance retention at 20 A g(-1)) when measured in a symmetrical two-electrode configuration in an aqueous electrolyte. The method described in this work provides a new route to prepare 2D electrode materials from a bulk precursor, thus exploiting their full potential for EDLCs.

Self-sacrifice Template Formation of Hollow Hetero-Ni7S6/Co3S4 Nanoboxes with Intriguing Pseudo-capacitance for High-performance Electrochemical Capacitors.

Herein, we report a simple yet efficient self-sacrifice template protocol to smartly fabricate hollow hetero-Ni7S6/Co3S4 nanoboxes (Ni-Co-S NBs). Uniform nickel cobalt carbonate nanocubes are first synthesized as the precursor via solvothermal strategy, and subsequently chemically sulfidized into hollow heter-Ni-Co-S NBs through anion-exchange process. When evaluated as electrode for electrochemical capacitors (ECs), the resultant hetero-Ni-Co-S NBs visually exhibit attractive pesudo-capacitance in KOH just after continuously cyclic voltammetry (CV) scanning for 100 cycles. New insights into the underlying energy-storage mechanism of the hollow hetero-Ni-Co-S electrode, based on physicochemical characterizations and electrochemical evaluation, are first put forward that the electrochemically induced phase transformation gradually occurrs during CV sweep from the hetero-Ni-Co-S to bi-component-active NiOOH and CoOOH, which are the intrinsic charge-storage phases for the appealing Faradaic capacitance (~677 F g(-1) at 4 A g(-1)) of hollow Ni-Co-S NBs at high rates after cycling. When further coupled with negative activated carbon (AC), the AC//hetero-Ni-Co-S asymmetric device with extended electrochemical window of 1.5 V demonstrates high specific energy density of ~31 Wh kg(-1). Of significance, we strongly envision that hollow design concept and new findings here hold great promise for enriching synthetic methodologies, and electrochemistry of complex metal sulfides for next-generation ECs.

Blockade of Serotonin 5-HT2A Receptors Suppresses Behavioral Sensitization and Naloxone-Precipitated Withdrawal Symptoms in Morphine-Treated Mice.

The increasing prescription of opioids is fueling an epidemic of addiction and overdose deaths. Morphine is a highly addictive drug characterized by a high relapse rate - even after a long period of abstinence. Serotonin (5-HT) neurotransmission participates in the development of morphine dependence, as well as the expression of morphine withdrawal. In this study, we examined the effect of blockade of 5-HT2A receptors (5-HT2ARs) on morphine-induced behavioral sensitization and withdrawal in male mice. 5-HT2AR antagonist MDL 11,939 (0.5 mg/kg, i.p.) suppressed acute morphine (5.0 mg/kg, s.c.)-induced increase in locomotor activity. Mice received morphine (10 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of morphine (10 mg/kg) was administered to induce the expression of behavioral sensitization. MDL 11,939 (0.5 mg/kg, i.p.) pretreatment suppressed the expression of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. MDL 11,939 (0.5 mg/kg, i.p.) prevented naloxone-precipitated withdrawal in morphine-dependent mice on day 7. Moreover, chronic morphine treatment increased 5-HT2AR protein level and decreased the phosphorylation of extracellular signal-regulated kinases in the prefrontal cortex. Together, these results by the first time demonstrate that 5-HT2ARs modulate opioid dependence and blockade of 5-HT2AR may represent a novel strategy for the treatment of morphine use disorders. HIGHLIGHTS: (i)Blockade of 5-HT2A receptors suppresses the expression of morphine-induced behavioral sensitization.(ii)Blockade of 5-HT2A receptors suppresses naloxone-precipitated withdrawal in morphine-treated mice.(iii)Chronic morphine exposure induces an increase in 5-HT2A receptor protein level and a decrease in ERK protein phosphorylation in prefrontal cortex.

Anion-Exchange Formation of Hollow NiCo2 S4 Nanoboxes from Mesocrystalline Nickel Cobalt Carbonate Nanocubes towards Enhanced Pseudocapacitive Properties.

An efficient anion-exchange protocol was investigated for the controllable fabrication of hollow NiCo2 S4 nanoboxes (NBs) from mesocrystalline nickel cobalt carbonate nanocubes as promising pseudocapacitive materials for electrochemical capacitors. The underlying processes of the formation of the hollow architecture were systematically investigated. Originating from the unique structural and compositional advantages, the resultant hollow NiCo2 S4 NB electrode with a loading of 5 mg cm2 delivered a large specific capacitance of 777 F g-1 at a high rate of 4 A g-1 in a three-electrode configuration with 6 m KOH as electrolyte. Furthermore, an asymmetric device constructed with the hollow NBs and activated carbon (AC) as positive and negative electrodes, respectively, showed extraordinary supercapacitance within an electrochemically operating voltage window from 0.0 to 1.5 V. The unique AC//NiCo2 S4 NB hybrid capacitor exhibited a large specific energy density (active mass normalized) of approximately 17.1 W h kg-1 at a high power density of 2250 W kg-1 , and desirable cycling durability with approximately 75 % specific capacitance retention after 5000 consecutive cycles at a current rate of 2 A g-1 . These electrochemical investigations strongly indicated that the as-fabricated hollow NiCo2 S4 NBs can be elegantly utilized as powerful candidates for advanced electrode platforms.

Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice.

Opioid abuse and dependence have evolved into an international epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to the opioid, for example morphine, can induce profound, long-lasting behavioral sensitization and physical dependence, which are thought to reflect neuroplasticity in neural circuitry. Central serotonin (5-HT) neurotransmission participates in the development of dependence on and the expression of withdrawal from morphine. Serotonin 5-HT(2C) receptor (5-HT(2C)R) agonists suppress psychostimulant nicotine or cocaine-induced behavioral sensitization and drug-seeking behavior; however, the impact of 5-HT(2C)R agonists on behaviors relevant to opioid abuse and dependence has not been reported. In the present study, the effects of 5-HT(2C)R activation on the behavioral sensitization and naloxone-precipitated withdrawal symptoms were examined in mice underwent repeated exposure to morphine. Male mice received morphine (10 mg/kg, s.c.) to develop behavioral sensitization. Lorcaserin, a 5-HT(2C)R agonist, prevented the induction and expression, but not the development, of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. Pretreatment of lorcaserin, or the positive control clonidine (an alpha 2-adrenoceptor agonist), ameliorated the naloxone-precipitated withdrawal symptoms. SB 242084, a selective 5-HT(2C)R antagonist, prevented the lorcaserin-mediated suppression of behavioral sensitization and withdrawal. Chronic morphine treatment was associated with an increase in the expression of 5-HT(2C)R protein in the ventral tegmental area, locus coeruleus and nucleus accumbens. These findings suggest that 5-HT(2C)R can modulate behavioral sensitization and withdrawal in morphine-dependent mice, and the activation of 5-HT(2C)R may represent a new avenue for the treatment of opioid addiction.