High-Pressure Synthesis and Stability Enhancement of Lithium Pentazolate.

The pentazolate anion, cyclo-N5-, has received extensive attention as a new generation of energetic species for explosive or propulsion applications. Binary pentazolate compounds have been obtained under high-pressure conditions and their stability enhancement is crucial for obtaining more competitive high energy density materials (HEDMs). Here, we report the synthesis of a new solid phase of lithium pentazolate (space group P21/c) through the chemical transformation of pure lithium azide under high-pressure and high-temperature conditions. Upon decompression, the structural transition from P21/c-LiN5 to P21/m-LiN5 at ∼15.6 GPa was observed for the first time. Cyclo-N5- can be traced down to ∼5.7 GPa at room temperature and recovered to ambient pressure under a low-temperature condition (80 K). Our results reveal the enhancement of pentazolate anion stability with the increasing content of metal cations and demonstrate that low temperature is an effective route for the recovery of the pentazolate anion.

Analysis of Muscular Electrical Activity and Blood Perfusion of Upper Extremity in Patients with Hemiplegic Shoulder Pain: A Pilot Study.

Background: Hemiplegic shoulder pain (HSP) is a common symptom for post-stroke patients, which has a severely adverse impact on their rehabilitation outcomes. However, the cause of HSP has not been clearly identified due to its complicated multifactorial etiologies. As possible causes of HSP, the abnormality of both muscular electrical activity and blood perfusion remains lack of investigations. Objective: This study aimed to analyze the alteration of muscular electrical activity and blood perfusion of upper extremity in patients with HSP by using surface electromyography (sEMG) and laser speckle contrast imaging (LSCI) measurement techniques, which may provide some insight into the etiology of HSP. Methods: In this observational and cross-sectional study, three groups of participants were recruited. They were hemiplegic patients with shoulder pain (HSP group), hemiplegic patients without shoulder pain (HNSP group), and healthy participants (Healthy group). The sEMG data and blood perfusion data were collected from all the subjects and used to compute three different physiological measures, the root-mean-square (RMS) and median-frequency (MDF) parameters of sEMG recordings, and the perfusion unit (PU) parameter of blood perfusion imaging. Results: The RMS parameter of sEMG showed significant difference (p < 0.05) in the affected side between HSP, HNSP, and Healthy groups. The MDF parameter of sEMG and PU parameter of blood perfusion showed no significant difference in both sides among the three groups (p > 0.05). The RMS parameter of sEMG showed a statistically significant correlation with the pain intensity (r = -0.691, p =0.012). Conclusion: This study indicated that the muscular electrical activity of upper extremity had a correlation with the presence of HSP, and the blood perfusion seemed to be no such correlation. The findings of the study suggested an alternative way to explore the mechanism and treatment of HSP.

Long noncoding RNA MEG3 silencing protects against hypoxia-induced pheochromocytoma-12 cell injury through inhibition of TIMP2 promoter methylation.

Hypoxia is a common pathological process caused by insufficient oxygen. Long noncoding RNAs (lncRNAs) have been proven to participate in this pathology. Hypoxia is reported to significantly reduce the secretion of tissue inhibitor of metalloproteinase 2 (TIMP2) and TIMP2 induces pheochromocytoma-12 (PC12) cell cycle arrest. Thus, our study aimed to explore the mechanism by which lncRNA maternally expressed gene 3 (MEG3) was implicated in hypoxia-induced PC12 cell injury through TIMP2 promoter methylation. To elucidate the potential biological significance of MEG3 and the regulatory mechanism between MEG3 and TIMP2, a hypoxia-induced PC12 cell injury model was generated. The hypoxia-exposed cells were subjected to a series of overexpression plasmids and short hairpin RNAs, followed by the measurement of levels of MEG3, TIMP2, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), Bcl-2-associated X protein, B-cell lymphoma-2, and caspase-3, as well as the changes in MMP, cell proliferation, apoptosis, and cell cycle progression. On the basis of the findings, MEG3 was upregulated in hypoxia-injured PC12 cells. MEG3 recruited methylation proteins DNMT3a, DNMT3b, and MBD1 and accelerated TIMP2 promoter methylation, which in turn inhibited its expression. Moreover, PC12 cells following MEG3 silencing and TIMP2 overexpression exhibited significantly decreased levels of LDH, MDA, and ROS along with cell apoptosis, yet increased SOD and MMP levels, as well as cell cycle entry to the S phase and cell proliferation. In conclusion, MEG3 silencing suppresses hypoxia-induced PC12 cell injury by inhibiting TIMP2 promoter methylation. This study may provide novel therapeutic targets for hypoxia-induced injury.

Effectiveness of Neuromuscular Electrical Stimulation on Lower Limbs of Patients With Hemiplegia After Chronic Stroke: A Systematic Review.

OBJECTIVE: To investigate the effectiveness of neuromuscular electrical stimulation (NMES) with or without other interventions in improving lower limb activity after chronic stroke. DATA SOURCES: Electronic databases, including PubMed, EMBase, Cochrane Library, PEDro (Physiotherapy Evidence Database), and PsycINFO, were searched from the inception to January 2017. STUDY SELECTION: We selected the randomized controlled trials (RCTs) involving chronic stroke survivors with lower limb dysfunction and comparing NMES or combined with other interventions with a control group of no electrical stimulation treatment. DATA EXTRACTION: The primary outcome was defined as lower limb motor function, and the secondary outcomes included gait speed, Berg Balance Scale, timed Up and Go, 6-minute walk test, Modified Ashworth Scale, and range of motion. DATA SYNTHESIS: Twenty-one RCTs involving 1481 participants were identified from 5759 retrieved articles. Pooled analysis showed that NMES had a moderate but statistically significant benefit on lower limb motor function (standard mean difference 0.42, 95% confidence interval 0.26-0.58), especially when NMES was combined with other interventions or treatment time within either 6 or 12 weeks. NMES also had significant benefits on gait speed, balance, spasticity, and range of motion but had no significant difference in walking endurance after NMES. CONCLUSIONS: NMES combined with or without other interventions has beneficial effects in lower limb motor function in chronic stroke survivors. These data suggest that NMES should be a promising therapy to apply in chronic stroke rehabilitation to improve the capability of lower extremity in performing activities.

Nicotinic Acetylcholine Receptor Alpha7 Subunit Mediates Vagus Nerve Stimulation-Induced Neuroprotection in Acute Permanent Cerebral Ischemia by a7nAchR/JAK2 Pathway.

BACKGROUND The role of nicotinic acetylcholine receptor alpha7 subunit (a7nAchR) in the treatment of acute cerebral ischemia by VNS has not been thoroughly clarified to date. Therefore, this study aimed to investigate the specific role of a7nAchR and explore whether this process is involved in the mechanisms of VNS-induced neuroprotection in rats undergoing permanent middle cerebral artery occlusion (PMCAO) surgery. MATERIAL AND METHODS Rats received a7nAChR antagonist (A) or antagonist placebo injection for control (AC), followed by PMCAO and VNS treatment, whereas the a7nAChR agonist (P) was utilized singly without VNS treatment but only with PMCAO pretreatment. The rats were randomly divided into 6 groups: sham PMCAO, PMCAO, PMCAO+VNS, PMCAO+VNS+A, PMCAO+VNS+AC, and PMCAO+P. Neurological function and cerebral infarct volume were measured to evaluate the level of brain injury at 24 h after PMCAO or PMCAO-sham. Moreover, the related proteins levels of a7nAChR, p-JAK2, and p-STAT3 in the ischemic penumbra were assessed by Western blot analysis. RESULTS Rats pretreated with VNS had significantly improved neurological function and reduced cerebral infarct volume after PMCAO injury (p<0.05). In addition, VNS enhanced the levels of a7nAchR, p-JAK2, and p-STAT3 in the ischemic penumbra (p<0.05). However, inhibition of a7nAchR not only attenuated the beneficial neuroprotective effects induced by VNS, but also decreased levels of p-JAK2 and p-STAT3. Strikingly, pharmacological activation of a7nAchR can partially substitute for VNS-induced beneficial neurological protection. CONCLUSIONS These results suggest that a7nAchR is a pivotal mediator of VNS-induced neuroprotective effects on PMCAO injury, which may be related to suppressed inflammation via activation of the a7nAchR/JAK2 anti-inflammatory pathway.

A study in persons later after stroke of the relationships between social participation, environmental factors and depression.

OBJECTIVE: To explore the impacts of social participation and the environment on depression among people with stroke. DESIGN: Cross-sectional survey. SETTING: Structured interviews in the participants' homes. SUBJECTS: Community-dwelling persons with stroke in the rural areas of China ( N = 639). INTERVENTIONS: Not applicable. MAIN MEASURES: Depression (Hamilton Rating Scale for Depression-6), activity and social participation (Chinese version of the World Health Organization's Disability Assessment Schedule 2.0), environmental barriers (Craig Hospital Inventory of Environmental Factors), neurological function (Canadian Neurological Scale). RESULTS: A total of 42% of the variance in depression was explained by the environmental barriers, neurological function, activity, and social participation factors studied. Social participation, services/assistance, and attitudes/support were directly related to depression; their standardized regression coefficients were 0.530, 0.162, and 0.092, respectively ( p ⩽ 0.01). The physical environment, policies, and neurological function indirectly impacted depression. Depression influences social participation in turn, with a standardized regression coefficient of 0.29 ( p ⩽ 0.01). CONCLUSIONS: Depression and social participation are inversely related. The physical environment, services/assistance, attitudes/support, and policies all impact post-stroke depression.

Involuntary, Forced and Voluntary Exercises Equally Attenuate Neurocognitive Deficits in Vascular Dementia by the BDNF-pCREB Mediated Pathway.

A rat model of vascular dementia was used to compare the effects of involuntary exercise induced by functional electrical stimulation (FES), forced exercise and voluntary exercise on the recovery of cognitive function recovery and its underlying mechanisms. In an involuntary exercise (I-EX) group, FES was used to induce involuntary gait-like running on ladder at 12 m/min. A forced exercise group (F-EX) and a voluntary exercise group (V-EX) exercised by wheel running. The Barnes maze was used for behavioral assessment. Brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element binding protein (CREB) positive cells in hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were evaluated using immunohistochemical methods. Western blotting was used to assess the levels of BDNF, phosphorylated protein kinase B (Akt), tropomyosin receptor kinase B (TrkB), mitogen-activated protein kinase 1 and 2 (MEK1/2), ERK1/2 and CREB in BDNF-pCREB signaling in the hippocampus and prefrontal cortex. Involuntary, forced and voluntary exercises were all found to reverse the cognitive deficits of vascular dementia with about equal effectiveness. The number of BDNF, pCREB and pERK1/2 immunopositive cells was significantly increased in the hippocampal CA1, CA2/3 and DG regions in all three exercise groups. In addition, involuntary exercise activated BDNF and the phosphorylation of Akt, TrkB, MEK1/2, ERK1/2 and CREB in the hippocampus and prefrontal cortex equally as well as voluntary or forced exercise. These results suggest that involuntary exercise induced by FES may be as beneficial for alleviating cognitive deficits after cerebral ischemia.

Agreement Between Single Raters and Team Rating When Applying the International Classification of Functioning, Disability and Health's Rehabilitation Set.

OBJECTIVE: To quantify the agreement between functional assessments by a single rater and a team using the Chinese version of the International Classification of Functioning, Disability and Health Rehabilitation Set in a clinical situation. DESIGN: Inter-rater, multi-centre agreement study. SUBJECTS: A total of 193 adult inpatients admitted to 5 rehabilitation centres at 5 hospitals in China Methods: The Chinese version of the International Classification of Functioning, Disability and Health Rehabilitation Set was used by either a single rater or a team to assess 193 patients at 5 Chinese hospitals. Percentage of agreement and quadratic-weighted kappa coefficients were computed. Evaluation times were compared with paired t-tests. RESULTS: The mean team and individual evaluation times were not significantly different. The percentage of agreement ranged from 46.1% to 94.2% depending on the item, and the quadratic-weighted kappas ranged from 0.43 to 0.92. Eight categories (26.6%) showed a weighted kappa exceeding 0.4, 11 others (36.7%) exceeded 0.6, and another 11 (36.7%) produced kappas of more than 0.8. CONCLUSION: Either a single rater or a team of raters can produce valid and consistent ratings when using the Chinese version of the International Classification of Functioning, Disability and Health Rehabilitation Set to assess patients in a rehabilitation department. The team rating approach is suitable for clinical application.

High-pressure synthesis of fully sp2-hybridized polymeric nitrogen layer in potassium supernitride.

Searching for fully sp2-hybridized layered structures is of fundamental importance because of their fascinating physical properties and potential to host topologically non-trivial electronic states. However, the synthesis of fully sp2-hybridized layered polymeric nitrogen structures remains a challenging work because of their low stability. Here, we report the synthesis of a fully sp2-hybridized layered polymeric nitrogen structure featuring fused 18-membered rings in potassium supernitride (K2N16) under high-pressure and high-temperature conditions. Bader charge analysis reveals that the potassium atomic layer stabilizes the unique sp2-hybridized polymeric nitrogen layers through the charge transfer effect in K2N16. The calculation of electronic structure indicates that K2N16 is a topological semimetal with multiple Dirac points and hosts higher-order Dirac fermions with cubic dispersion, which are contributed by the sp2-hybridized polymeric nitrogen layers arranged in P6/mcc symmetry. The high-pressure synthesis of the fully sp2-hybridized polymeric nitrogen layered structure provides promising prospects for exploring novel topological materials with effective stabilization routes.

Synergy Analysis of Back Muscle Activities in Patients With Adolescent Idiopathic Scoliosis Based on High-Density Electromyogram.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a common structural spinal deformity and is typically associated with altered muscle properties. However, it is still unclear how muscle activities and the underlying neuromuscular control are changed in the entire scoliotic zone, restricting the corresponding pathology investigation and treatment enhancements. METHODS: High-density electromyogram (HD-EMG) was utilized to explore the neuromuscular synergy of back muscle activities. For each of ten AIS patients and ten healthy subjects for comparison, an HD-EMG array was placed on their back from T8 to L4 to record EMG signals when performing five spinal motions (flexion/extension, lateral bending, axial rotation, siting, and standing). From the HD-EMG recordings, muscle synergies were extracted using the non-negative matrix factorization method and the topographical maps of EMG root-mean-square were constructed. RESULTS: For both the AIS and healthy subjects, the experimental results indicated that two muscle synergy groups could explain over 90% of recorded muscle activities for all five motions. During flexion/extension, the patients presented statistically significant higher activations on the convex side in the entire root-mean-square maps and synergy vector maps (p < 0.05). During lateral bending and axial rotation, the patients exhibited less activated muscles on the dominant actuating side relative to the contralateral side and their synergy vector maps showed a less homogenous and more diffuse distribution of muscle contraction with statistically different centers of gravity. CONCLUSION: The findings suggest a scoliotic spine might adopt an altered modular muscular coordination strategy to actuate different dominant muscles as adapted compensations for the deformation.

Effect of Electroacupuncture on Shoulder Subluxation in Poststroke Patients with Hemiplegic Shoulder Pain: A Sham-Controlled Study Using Multidimensional Musculoskeletal Ultrasound Assessment.

OBJECTIVE: This study aimed to use multidimensional musculoskeletal ultrasound imaging technique to investigate the effect of electroacupuncture (EA) on shoulder subluxation in poststroke patients with hemiplegic shoulder pain. METHODS: In this prospective single-blind, randomized, sham-controlled study, thirty-four patients with shoulder subluxation and hemiplegic shoulder pain were recruited and randomly assigned into the EA group or the sham EA (SEA) group. In the EA group, EA was applied to the Jian yu (LI15), Bi nao (LI14), Jian zhen (SI9), and Jian liao (TE14) acupoints. In the SEA group, the EA was applied 15 mm away from the Lou gu (SP7), Di ji (SP8), Jiao xin (KI8), and Zhu bin (KI9) acupoints. Both groups underwent treatment 30 minutes/day, five days a week, for two weeks using dense waves with a frequency of 2/100 Hz. A Visual Analogue Scale (VAS) was used to evaluate the effectiveness of treatment in reducing shoulder pain. Musculoskeletal ultrasound was used to evaluate the changes of measures of shoulder subluxation in multidimensions (i.e., the acromiohumeral distance, AHD; acromion-greater tuberosity, AGT; and acromion-lesser tuberosity, ALT). Both the within- and between-groups treatment effects were assessed. RESULTS: The pain intensity measured by VAS and shoulder subluxation measured by musculoskeletal ultrasound (i.e., AHD, AGT, and ALT) showed significant (p < 0.05) within-group difference in both groups. The between-group difference appeared in the pain intensity (p < 0.05), while it disappeared in the three measures of shoulder subluxation (p > 0.05). CONCLUSIONS: Using VAS for measuring pain intensity and multidimensional musculoskeletal ultrasound imaging technique for measuring shoulder subluxation, this study finds that the hemiplegic shoulder pain can be improved significantly by the EA while the shoulder subluxation cannot be. Our findings further reveal the analgesic mechanism of EA on hemiplegic shoulder pain following stroke.

Exercise improves recognition memory and synaptic plasticity in the prefrontal cortex for rats modelling vascular dementia.

OBJECTIVES: Functional electrical stimulation (FES) may induce involuntary exercise and make beneficial effects on vascular dementia (VD) by strengthening the BDNF-pCREB-mediated pathway and hippocampal plasticity. Whether FES improves recognition memory and synaptic plasticity in the prefrontal cortex (PFC) was investigated by establishing a VD model. METHODS: The VD rats were administered with two weeks of voluntary exercise, forced exercise, or involuntary exercise induced with FES. Sham-operated and control groups were also included. The behavioral changes were assessed with the novel object recognition test and novel object location test. The expression levels of key proteins related to synaptic plasticity in the PFC were also detected. RESULTS: All types of exercise improved the rats' novel object recognition index, but only voluntary exercise and involuntary exercise induced with FES improved the novel object location index. Any sort of exercise enhanced the expression of key proteins in the PFC. CONCLUSION: Involuntary exercise induced with FES can improve recognition memory in VD better than forced exercise. The mechanism is associated with increased synaptic plasticity in the PFC. FES may be a useful alternative tool for cognitive rehabilitation.

[Mechanism of electroacupuncture on "Zusanli (ST 36)" for chemotherapy-induced peripheral neuropathy].

OBJECTIVE: To observe the effects and duration of electroacupuncture on the mechanical pain threshold induced by paclitaxel and explore its analgesic mechanism. METHODS: Sixty-four C57BL/6J male mice were randomly divided into 4 groups, a normal+sham EA group, a normal+EA group, a medicine+sham EA(Med+ sham EA) group, a medicine + EA (Med + EA) group, 16 cases in each group. The model of chemotherapy-induced peripheral neuropathy was established with paclitaxel intraperitoneal injection on the 1st, 3rd, 5th, 7th day in the Med + sham EA group and the Med + EA group. EA of 30 min was used on bilateral "Zusanli (ST 36)" on the 9th, 11th, 13th, 16th, 18th, 20th, 23rd, 25th, 27th, 30th day in the EA groups, 2 Hz/100 Hz and 1~ 1.5 mA. Acupuncture was applied on the same acupoint at the same times in the sham EA groups. Mechanical pain thresholds were tested by VonFrey before and after model establishment, namely on the 8th, 14th; 21st and, 28th day. The heart blood of 8 mice was drawn quickly to collect serum in every group on the 31st day, and the contents of tumor necrosis factor α (TNF-α), interleukin-1α (IL-1α), interleukin-1ß (IL-1ß) in proinflammatory cytokine were examined by ELISA. Mechanical pain thresholds were tested by VonFrey for the rest 8 mice of each group until there was no apparent difference in the two paclitaxel groups once a week,namely on the 35th, 42nd, 49th day. RESULTS: The pain thresholds of each group were not statistically different before model establishment (P > 0.05). After model establishment (on the 8th day), thresholds of the paclitaxel groups were lower than those of the normal groups (all P < 0.05). After EA, the mechanical pain thresholds of the Med + EA group were higher than those of the Med + sham EA group at all the time points, and there was statistical difference on the 14th, 21st and 28th day (all P < 0.05). The analgesic effect was lasting to the 49th day. The contents of TNF-α, IL-1α, IL-1ß of the Med + EA group were decreased than those of the Med+sham EA group in different degree, with statistical significance of IL-1α (P < 0.05). CONCLUSION: EA can effectively treat paclitaxel-induced peripheral neuropathy,and the analgesic mechanism is probably related to decreasing the proinflammatory cytokine.

Involuntary, forced and voluntary exercises are equally capable of inducing hippocampal plasticity and the recovery of cognitive function after stroke.

OBJECTIVES: Forced and voluntary exercises are known to improve cognition and induce neuroprotection after stroke, however, any effects of involuntary movement induced by functional electrical stimulation (FES) are unclear. The effects of involuntary exercise induced by FES, forced and voluntary exercise on the recovery of cognitive function in vascular dementia and the regional repair of ischaemic lesions were investigated using a rat model. METHODS: Wistar rats were randomly assigned to a sham group, a vascular dementia control group (VD), an involuntary exercise group (I-Ex), a forced exercise group (F-Ex) or a voluntary exercise group (V-Ex). An object recognition test (ORT) and an object location test (OLT) were used to evaluate the recovery of cognitive function. Levels of synapsin I (SYN), synaptophysin (SYP), postsynaptic density 95 (PSD-95), microtubule-associated protein 2 (MAP-2) and Tau in the hippocampus were evaluated using western blotting and immunohistochemistry. Nissl staining was applied to visualise the loss of viable neurons from the hippocampus. RESULTS: Involuntary exercise and voluntary exercise both improved cognition in terms of ORT and OLT results. Forced exercise only improved ORT results. The levels of SYN, PSD-95, MAP-2 and Tau in the hippocampus were enhanced by all three patterns of exercise training. Moreover, all three patterns reduced losses of dendrons and neurons in the hippocampal CA1 and CA2 zones, but without significant differences among the three exercise regimens. CONCLUSION: Involuntary exercise induced by FES has beneficial effects on cognitive function after vascular dementia comparable to those of forced and voluntary exercise.

Electroacupuncture promotes neural stem cell proliferation and neurogenesis in the dentate gyrus of rats following stroke via upregulation of Notch1 expression.

Neural stem cells (NSCs) are important in rehabilitation following stroke. Electroacupuncture (EA) treatment has been observed to promote the recovery of neurological functions subsequent to stroke, however, the effects of EA on the proliferation and differentiation of NSCs and its potential mechanisms remain to be elucidated. In the present study, rats, in which a stroke was induced through middle cerebral artery occlusion (MCAO), were treated with EA or control manipulation for 21 days. The modified Neurological Severity score and Morris water maze tests were used to assess the neurological functions of the rats. Bromodeoxyuridine (BrdU)/glial fibrillary acidic protein (GFAP) or BrdU/neuronal marker (NeuN) double immunofluorescence staining were used to examine the proliferation and differentiation of the NSCs. Reverse transcription quantitative polymerase chain reaction (RT­qPCR) and western blot analyses were performed to detect the expression levels of Notch1 and Hes1 in the dentate gyrus (DG) of the hippocampus of rats following MCAO. The results demonstrated that EA treatment significantly improved the neurological functional recovery of rats following stroke. A significant increase was observed in the number of BrdU+/GAFP+ and BrdU+/NeuN+ cells in the DG area in the EA­treated rats compared with that of the control group. RT­qPCR analysis revealed that EA treatment significantly increased the expression levels of Notch1 and Hes1, which may account for the enhanced proliferation and differentiation of NSCs. In conclusion, to the best of our knowledge, the present study was the first to demonstrate that EA treatment promoted NSC proliferation and neurogenesis in the DG area through the upregulation of Notch signaling following a stroke; therefore, EA may be a useful novel therapeutic strategy in future stroke treatment.