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1.
Zhongguo Zhen Jiu ; 43(12): 1343-1350, 2023 Dec 12.
Article in English, Chinese | MEDLINE | ID: mdl-38092530

ABSTRACT

OBJECTIVES: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. METHODS: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined;with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. RESULTS: Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). CONCLUSIONS: Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.


Subject(s)
Acupuncture Therapy , Cognitive Dysfunction , Diabetes Mellitus, Type 2 , Electroacupuncture , Humans , Acupuncture Points , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Glycated Hemoglobin , Cognitive Dysfunction/etiology , Cognitive Dysfunction/therapy , Cholesterol , gamma-Aminobutyric Acid
2.
Mikrochim Acta ; 190(10): 415, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37750999

ABSTRACT

In recent years, electrochemiluminescence resonance energy transfer (ECL-RET) with low background signal and high specificity has attracted much attention among researchers. Herein, we established a novel ECL-RET biosensor for PML/RARα fusion gene detection. In this ECL-RET system, carbon dots (CDs) with low toxicity and prominent electrochemical activity were used as donor and Au@Ag2S core-shell nanoparticles (Au@Ag2S NPs) were employed as ECL acceptor. The Au@Ag2S NPs possessed a wide ultraviolet-visible (UV-vis) absorption spectrum between 500 nm and 700 nm, which completely overlapped with the ECL spectrum of CDs. Furthermore, the CDs-decorated poly-amidoamine/reduced graphene oxide (CDs/PAMAM/rGO) nanocomposites were prepared to improve the ECL signals and served as a substrate to stably load capture probe deoxyribonucleic acid (DNA). Based on the ECL-RET biosensing strategy, the Au@Ag2S NPs-labeled assistant probes and target DNA could pair with capture probes to form the sandwich-type DNA structure and the distance between donor and accepter was closed, leading to quenching of the ECL signal of CDs. The ECL-RET biosensor represented eminent analytical performance for PML/RARα fusion gene detection with a wide linear relationship from 5 fM to 500 pM and a low detection limit of 0.72 fM, which provided a novel technical means and theoretical basis for detection and diagnosis of acute promyelocytic leukemia.


Subject(s)
Nanocomposites , Nanoparticles , Carbon , Energy Transfer , DNA
3.
Biosens Bioelectron ; 238: 115583, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37573643

ABSTRACT

Since microRNAs (miRNAs) are predictors of tumorigenesis, accurate identification and quantification of miRNAs with highly similar sequences are expected to reflect tumor diagnosis and treatment. In this study, a highly selective and sensitive electrochemiluminescence (ECL) biosensor was constructed for miRNAs determination based on Y-shaped junction structure equipped with locked nucleic acids (LNA), graphene oxide-based nanocomposite to enrich luminophores, and conductive matrix. Specifically, two LNA-modified probes were designed for specific miRNA recognition, that is, a dual-amine functionalized hairpin capture probe and a signal probe. A Y-shaped DNA junction structure was generated on the electrode surface upon miRNA hybridizing across the two branches, so as to enhance the selectivity. Carbon quantum dots-polyethylene imine-graphene oxide (CQDs-PEI-GO) nanocomposites were developed to enrich luminophores CQDs, and thus enhancing the ECL intensity. For indirect signal amplification, an electrochemically activated poly(2-aminoterephthalic acid) (ATA) film decorated with gold nanoparticles was prepared on electrode as an effective matrix to accelerate the electron transfer. The fabricated ECL biosensor achieved sensitive determination of miRNA-222 with a limit-of-detection (LOD) as low as 1.95 fM (S/N = 3). Notably, Y-shaped junction structures equipped with LNA probes endowed ECL biosensor with salient single-base discrimination ability and anti-interference capacity. Overall, the proposed Y-shaped ECL biosensor has considerable promise for clinical biomarker determination.


Subject(s)
Biosensing Techniques , Metal Nanoparticles , MicroRNAs , Quantum Dots , MicroRNAs/genetics , Carbon/chemistry , Quantum Dots/chemistry , Gold/chemistry , Luminescent Measurements , Metal Nanoparticles/chemistry , DNA/chemistry , Nucleic Acid Probes , Polyethyleneimine/chemistry , Electrochemical Techniques
4.
Science ; 381(6656): eadd6696, 2023 07 28.
Article in English | MEDLINE | ID: mdl-37499037

ABSTRACT

Aggregation of tau into filamentous inclusions underlies Alzheimer's disease (AD) and numerous other neurodegenerative tauopathies. The pathogenesis of tauopathies remains unclear, which impedes the development of disease-modifying treatments. Here, by systematically analyzing human tripartite motif (TRIM) proteins, we identified a few TRIMs that could potently inhibit tau aggregation. Among them, TRIM11 was markedly down-regulated in AD brains. TRIM11 promoted the proteasomal degradation of mutant tau as well as superfluous normal tau. It also enhanced tau solubility by acting as both a molecular chaperone to prevent tau misfolding and a disaggregase to dissolve preformed tau fibrils. TRIM11 maintained the connectivity and viability of neurons. Intracranial delivery of TRIM11 through adeno-associated viruses ameliorated pathology, neuroinflammation, and cognitive impairments in multiple animal models of tauopathies. These results suggest that TRIM11 down-regulation contributes to the pathogenesis of tauopathies and that restoring TRIM11 expression may represent an effective therapeutic strategy.


Subject(s)
Protein Aggregation, Pathological , Tauopathies , Animals , Humans , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Brain/metabolism , Neurons/metabolism , tau Proteins/genetics , tau Proteins/metabolism , Tauopathies/genetics , Tauopathies/metabolism , Tripartite Motif Proteins/genetics , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
5.
Chemistry ; 29(46): e202301124, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37296528

ABSTRACT

NiFe-layered double hydroxide (NiFe-LDH) is the benchmark catalyst for the oxygen evolution reaction (OER) in alkaline medium, however, it is still challenging to improve its activity and stability. Herein, NiFe-LDH macroporous array electrodes are demonstrated to significantly enhance the activity and stability for oxygen evolution reaction. The electrodes are fabricated by the chemical and electrochemical corrosion process of Ni foam induced by ferric nitrate, hydrochloric acid and oxygen. By optimizing the amount of iron salt and acid and selecting the appropriate reaction temperature and time, the NiFe-LDH electrodes only need the overpotential of 180 mV and 248 mV to reach the current density of 10 mA cm-2 and 500 mA cm-2 , respectively, and remain highly stable for 1000 h at 500 mA cm-2 . The unique macroporous array not only significantly increases the active area of NiFe-LDH catalyst, but also creates a stable nanostructure that avoids severe reconstruction.

6.
Small ; 19(36): e2301609, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37116125

ABSTRACT

NiFe-based (oxy)hydroxides are the benchmark catalysts for the oxygen evolution reaction (OER) in alkaline medium, however, it is still challenging to control their structures and compositions. Herein, molybdates (NiFe(MoO4 )x ) are applied as unique precursors to synthesize ultrafine Mo modified NiFeOx Hy (oxy)hydroxide nanosheet arrays. The electrochemical activation process enables the molybdate ions (MoO4 2- ) in the precursors gradually dissolve, and at the same time, hydroxide ions (OH- ) in the electrolyte diffuse into the precursor and react with Ni2+ and Fe3+ ions in confined space to produce ultrafine NiFeOx Hy (oxy)hydroxides nanosheets (<10 nm), which are densely arranged into microporous arrays and maintain the rod-like morphology of the precursor. Such dense ultrafine nanosheet arrays produce rich edge planes on the surface of NiFeOx Hy (oxy)hydroxides to expose more active sites. More importantly, the capillary phenomenon of microporous structures and hydrophilic hydroxyl groups induce the superhydrophilicity and the rough surface produces the superaerophobic characteristic for bubbles. With these advantages, the optimized catalyst exhibits excellent performance for OER, with a small overpotential of 182 mV at 10 mA cm-2 and long-term stability (200 h) at 200 mA cm-2 . Theoretical calculations show that the modification of Mo enhances the electron delocalization and optimizes the adsorption of intermediates.

7.
Mikrochim Acta ; 190(2): 75, 2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36700977

ABSTRACT

Benzotriazole UV stabilizers (BUVSs) are a class of emerging contaminants of concern; the development of rapid and convenient monitoring method for these trace-level pollutants in waters is of crucial significance in environmental science. Here, a novel magnetic flower-like molybdenum disulfide/cobalt ferrite nanocomposite (MoS2/CoFe2O4) was synthesized by hydrothermal reaction. Compared with the conventional Fe3O4-based magnetic composites, the proposed material just required a minimum consumption of Co/Fe towards the equivalent of MoS2 while providing superior magnetization performance. Taking advantages of high adsorption capacity, extraordinary stability, and repeatability in construction, MoS2/CoFe2O4 was applied to the extraction to BUVSs. The enrichment factors of three BUVSs were in the range 164-193 when 20 mL of environmental water sample was loaded on 40 mg of the adsorbent. MoS2/CoFe2O4 could be regenerated and recycled at least 10 cycles of adsorption/desorption with recoveries of 80.1-111%. The method of MoS2/CoFe2O4-based extraction coupled with high-performance liquid chromatography-variable wavelength detector was applied to the monitoring of BUVSs in seawater, lake water, and wastewater, which gave detection limits (S/N = 3) of 0.023-0.030 ng·mL-1 and recoveries of 80.1-110%. The intra-day and inter-day precisions (relative standard deviation, RSDs, n = 3) were in the range 1.6-7.5% and 3.2-11.5%, respectively. The approach is an alternative for efficient and sensitive extraction and determination of trace-level environmental pollutants in waters.

8.
AMB Express ; 12(1): 130, 2022 Oct 09.
Article in English | MEDLINE | ID: mdl-36210372

ABSTRACT

Alkaline pectate lyase has developmental prospects in the textile, pulp, paper, and food industries. In this study, we selected BacPelA, the pectin lyase with the highest expression activity from Bacillus clausii, modified and expressed in Escherichia coli BL21(DE3). Through fragment replacement, the catalytic activity of the enzyme was significantly improved. The optimum pH and temperature of the modified pectin lyase (PGLA-rep4) were 11.0 and 70 °C, respectively. It also exhibited a superior ability to cleave methylated pectin. The enzyme activity of PGLA-rep4, measured at 235 nm with 0.2% apple pectin as the substrate, was 554.0 U/mL, and the specific enzyme activity after purification using a nickel column was 822.9 U/mg. After approximately 20 ns of molecular dynamics simulation, the structure of the pectin lyase PGLA-rep4 tended to be stable. The root mean square fluctuation (RMSF) values at the key catalytically active site, LYS168, were higher than those of the wildtype PGLA. In addition, PGLA-rep4 was relatively stable in the presence of metal ions. PGLA-rep4 has good enzymatic properties and activities and maintains a high pH and temperature. This study provides a successful strategy for enhancing the catalytic activity of PGLA-rep4, making it the ultimate candidate for degumming and various uses in the pulp, paper, and textile industries.

9.
Int J Nanomedicine ; 16: 3497-3508, 2021.
Article in English | MEDLINE | ID: mdl-34045854

ABSTRACT

PURPOSE: The PML/RARα fusion gene as a leukemogenesis plays a significant role in clinical diagnosis of the early stage of acute promyelocytic leukemia (APL). Here, we present an electrochemical biosensor for PML/RARα fusion gene detection using carbon dots functionalized graphene oxide (CDs/GO) nanocomposites modified glassy carbon electrode (CDs/GO/GCE). MATERIALS AND METHODS: In this work, the CDs/GO nanocomposites are produced through π-π stacking interaction and could be prepared in large quantities by a facile and economical way. The CDs/GO nanocomposites were decorated onto electrode surface to improve the electrochemical activity and as a bio-platform attracted the target deoxyribonucleic acid (DNA) probe simultaneously. RESULTS: The CDs/GO/GCE was fabricated successfully and exhibits high electrochemical activity, good biocompatibility, and strong bioaffinity toward the target DNA sequences, compared with only the pristine CDs on GCE or GO on GCE. The DNA biosensor displays excellent sensing performance for detecting the relevant pathogenic DNA of APL with a detection limit of 83 pM (S/N = 3). CONCLUSION: According to the several experimental results, we believe that the simple and economical DNA biosensor has the potential to be an effective and powerful tool for detection of pathogenic genes in the clinical diagnosis.


Subject(s)
Biosensing Techniques/methods , Carbon/chemistry , DNA/genetics , Gene Fusion/genetics , Graphite/chemistry , Nanocomposites/chemistry , Oncogene Proteins, Fusion/genetics , Biosensing Techniques/instrumentation , Electrochemistry , Electrodes , Humans
10.
Mikrochim Acta ; 187(9): 540, 2020 09 02.
Article in English | MEDLINE | ID: mdl-32876888

ABSTRACT

A novel zeolite imidazole framework@hydroxyapatite composite (ZIF-8@HAP) was constructed via in-situ growth and developed for efficient dispersive solid-phase extraction (DSPE) of three benzodiazepines from urine samples. The prepared composite was characterized by scanning electron microscopy, energy-dispersive spectrometer, Fourier-transform infrared spectrometry, X-ray diffractometry, zeta potential analyzer, and nitrogen adsorption-desorption experiment. Characterization results showed typical dodecahedron ZIF-8 crystals that were uniformly located on the surface of rod-like HAP. The combination of ZIF-8 and HAP made the surface area significantly enhanced from 4.68 to 205.44 m2 g-1. Compared with a commercial C18 adsorbent, ZIF-8@HAP exhibited superior removal performance for interfering components from urine and offered better extraction properties for the analytes. The prepared ZIF-8@HAP was applied as an adsorbent in DSPE, and the main experimental parameters, including pH and ionic strength of solution, adsorbent amount, adsorption time, elution solvent, and volume, were investigated. Under optimal conditions, the adsorption for 250 ng mL-1 of each analyte in 4 mL of urine was accomplished within 2 min using 60 mg of adsorbent. The method of ZIF-8@HAP-based DSPE followed by high-performance liquid chromatography gave enhancement factors of 13.3-15.3, linear ranges of 2.5-500 ng mL-1, and limits of detection (S/N = 3) of 0.7-1.4 ng mL-1. The relative recoveries at three spiked levels ranged from 88.7 - 102% with intra-day and inter-day precisions from 3.0 - 10.3% and 2.3 - 12.3%, respectively. These results indicated that the proposed strategy had promising applicability for convenient, rapid, and efficient determination of benzodiazepines in urine samples.Graphical abstract In-situ fabrication of ZIF-8@HAP composite for dispersive solid-phase extraction of benzodiazepines in urine samples.


Subject(s)
Benzodiazepines/therapeutic use , Chromatography, High Pressure Liquid/methods , Durapatite/chemistry , Solid Phase Extraction/methods , Zeolites/chemistry , Benzodiazepines/pharmacology , Humans
11.
Sci Signal ; 13(638)2020 06 30.
Article in English | MEDLINE | ID: mdl-32606037

ABSTRACT

N-methyl-d-aspartate (NMDA) glutamate receptors (NMDARs) containing GluN2B subunits are prevalent early after birth in most brain regions in rodents. Upon synapse maturation, GluN2B is progressively removed from synapses, which affects NMDAR function and synaptic plasticity. Aberrant recruitment of GluN2B into mature synapses has been implicated in several neuropathologies that afflict adults. We found that the E3 ubiquitin ligase Cbl-b was enriched in the spinal cord dorsal horn neurons of mice and rats and suppressed GluN2B abundance during development and inflammatory pain. Cbl-b abundance increased from postnatal day 1 (P1) to P14, a critical time period for synapse maturation. Through its N-terminal tyrosine kinase binding domain, Cbl-b interacted with GluN2B. Ubiquitination of GluN2B by Cbl-b decreased the synaptic transmission mediated by GluN2B-containing NMDARs. Knocking down Cbl-b in vivo during P1 to P14 led to sustained retention of GluN2B at dorsal horn synapses, suggesting that Cbl-b limits the synaptic abundance of GluN2B in adult mice. However, peripheral inflammation induced by intraplantar injection of complete Freund's adjuvant resulted in the dephosphorylation of Cbl-b at Tyr363, which impaired its binding to and ubiquitylation of GluN2B, enabling the reappearance of GluN2B-containing NMDARs at synapses. Expression of a phosphomimic Cbl-b mutant in the dorsal horn suppressed both GluN2B-mediated synaptic currents and manifestations of pain induced by inflammation. The findings indicate a ubiquitin-mediated developmental switch in NMDAR subunit composition that is dysregulated by inflammation, which can enhance nociception.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Nociception , Proto-Oncogene Proteins c-cbl/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Spinal Cord Dorsal Horn/metabolism , Synapses/metabolism , Ubiquitination , Animals , Male , Mice , Pain/metabolism , Pain/pathology , Rats , Rats, Sprague-Dawley , Spinal Cord Dorsal Horn/pathology , Synapses/pathology
12.
Medicine (Baltimore) ; 99(25): e20483, 2020 Jun 19.
Article in English | MEDLINE | ID: mdl-32569169

ABSTRACT

BACKGROUND: This study will assess the effectiveness and safety of neuromuscular electrical stimulation (NMES) for endometriosis-related pain (ERP). METHODS: Seven electronic databases of Cochrane Library, PUBMED, EMBASE, WANGFANG, VIP, CBM, and CNKI will be searched. We will search all electronic databases related the randomized controlled trials (RCTs) on the effectiveness and safety of NMES for ERP up to the March 31, 2020 without restrictions of language. RevMan 5.3 software will be used for risk of bias assessment, related data analysis and meta-analysis. RESULTS: This systematic review and meta-analysis will summarize current high-quality RCTs on the effectiveness and safety of NMES for ERP. Results of this study will provide the basis for both clinician and further research. CONCLUSION: This study will investigate whether NMES is effective and safety for the treatment of ERP. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040191.


Subject(s)
Electric Stimulation Therapy , Endometriosis/complications , Pain Management , Female , Humans , Meta-Analysis as Topic , Pain/etiology , Systematic Reviews as Topic
13.
Chemistry ; 26(22): 5037-5050, 2020 Apr 16.
Article in English | MEDLINE | ID: mdl-32022324

ABSTRACT

A facile approach to the synthesis of diaryl- and dialkyl-substituted monophosphino-o-carboranes by rhodium(I)-catalyzed phosphine-directed B3,6 -H activation has been developed for the first time. Upon switching rhodium(I) to palladium(II), C-arylated and B6 -halogenated products were obtained by using tBuOLi and Li2 CO3 as base, respectively. These discoveries provide some simple and efficient approaches to the modification of monophosphino-o-carboranes.

14.
PLoS Biol ; 17(8): e3000371, 2019 08.
Article in English | MEDLINE | ID: mdl-31433808

ABSTRACT

Inhibitory glycinergic transmission in adult spinal cord is primarily mediated by glycine receptors (GlyRs) containing the α1 subunit. Here, we found that α1ins, a longer α1 variant with 8 amino acids inserted into the intracellular large loop (IL) between transmembrane (TM)3 and TM4 domains, was expressed in the dorsal horn of the spinal cord, distributed at inhibitory synapses, and engaged in negative control over nociceptive signal transduction. Activation of metabotropic glutamate receptor 5 (mGluR5) specifically suppressed α1ins-mediated glycinergic transmission and evoked pain sensitization. Extracellular signal-regulated kinase (ERK) was critical for mGluR5 to inhibit α1ins. By binding to a D-docking site created by the 8-amino-acid insert within the TM3-TM4 loop of α1ins, the active ERK catalyzed α1ins phosphorylation at Ser380, which favored α1ins ubiquitination at Lys379 and led to α1ins endocytosis. Disruption of ERK interaction with α1ins blocked Ser380 phosphorylation, potentiated glycinergic synaptic currents, and alleviated inflammatory and neuropathic pain. These data thus unraveled a novel, to our knowledge, mechanism for the activity-dependent regulation of glycinergic neurotransmission.


Subject(s)
Posterior Horn Cells/metabolism , Receptors, Glycine/metabolism , Animals , Extracellular Signal-Regulated MAP Kinases/metabolism , Glycine/metabolism , MAP Kinase Signaling System/physiology , Male , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 7/metabolism , Phosphorylation , Receptor, Metabotropic Glutamate 5/metabolism , Receptor, Metabotropic Glutamate 5/physiology , Receptors, Glycine/physiology , Signal Transduction/physiology , Spinal Cord/metabolism , Spinal Cord Dorsal Horn/metabolism , Spine/metabolism , Synapses/metabolism , Synaptic Transmission/physiology
15.
Neuropharmacology ; 148: 358-365, 2019 04.
Article in English | MEDLINE | ID: mdl-30721695

ABSTRACT

Glycine receptors (GlyRs) are pentameric proteins that consist of α (α1-α4) subunits and/or ß subunit. In the spinal cord of adult animals, the majority of inhibitory glycinergic neurotransmission is mediated by α1 subunit-containing GlyRs. The reduced glycinergic inhibition (disinhibition) is proposed to increase the excitabilities and spontaneous activities of spinal nociceptive neurons during pathological pain. However, the molecular mechanisms by which peripheral lesions impair GlyRs-α1-mediated synaptic inhibition remain largely unknown. Here we found that activity-dependent ubiquitination of GlyRs-α1 subunit might contribute to glycinergic disinhibition after peripheral inflammation. Our data showed that HUWE1 (HECT, UBA, WWE domain containing 1), an E3 ubiquitin ligase, located at spinal synapses and specifically interacted with GlyRs-α1 subunit. By ubiquitinating GlyRs-α1, HUWE1 reduced the surface expression of GlyRs-α1 through endocytic pathway. In the dorsal horn of Complete Freund's Adjuvant-injected mice, shRNA-mediated knockdown of HUWE1 blunted GlyRs-α1 ubiquitination, potentiated glycinergic synaptic transmission and attenuated inflammatory pain. These data implicated that ubiquitin modification of GlyRs-α1 represented an important way for peripheral inflammation to reduce spinal glycinergic inhibition and that interference with HUWE1 activity generated analgesic action by resuming GlyRs-α1-mediated synaptic transmission.


Subject(s)
Neural Inhibition/physiology , Receptors, Glycine/physiology , Spinal Cord Dorsal Horn/physiopathology , Tumor Suppressor Proteins/physiology , Ubiquitin-Protein Ligases/physiology , Ubiquitination/drug effects , Animals , Cells, Cultured , Humans , Male , Mice , Neural Inhibition/drug effects , Pain/prevention & control , RNA, Small Interfering/pharmacology , Receptors, Glycine/drug effects , Receptors, Glycine/metabolism , Synaptic Transmission/drug effects , Tumor Suppressor Proteins/antagonists & inhibitors , Tumor Suppressor Proteins/pharmacology , Ubiquitin-Protein Ligases/antagonists & inhibitors , Ubiquitin-Protein Ligases/pharmacology
16.
Org Lett ; 20(24): 7816-7820, 2018 12 21.
Article in English | MEDLINE | ID: mdl-30540198

ABSTRACT

A novel visible-light-promoted C-P bond formation reaction in the absence of both transition metal and photoredox catalysts is disclosed. By employing easily available and inexpensive heteroaryl chlorides/bromides as substrates, a variety of heteroaryl phosphine oxides were obtained in moderate to good yields. This strategy provides a simple and efficient route to heteroaryl phosphine oxides.

17.
Nanoscale Res Lett ; 13(1): 267, 2018 Sep 04.
Article in English | MEDLINE | ID: mdl-30182207

ABSTRACT

In this paper, a laterally coupled distributed feedback (LC-DFB) laser based on modulation p-doped multiple InAs/GaAs quantum dot (QD) structures has been fabricated. The device exhibits a high side-mode suppression ratio (SMSR) of > 47 dB and a high thermal stability of dλ/dT = 0.092 nm/K under continuous-wave (CW) operation, which is mainly attributed to the high material gain prepared by modulation p-doping and rapid thermal annealing (RTA) process, and the significantly reduced waveguide losses by shallow-etched gratings and its close proximity to the laser ridge feature in the LC-DFB laser. With this superior performance of the DFB laser, the wide tunable dual-wavelength lasing operation has been obtained by delicately defining different periods for the grating structures on the two sides of the laser ridge or combining the reduced laser cavity length. The wavelength spacing between the two lasing modes can be flexibly tuned in a very wide range from 0.5 to 73.4 nm, corresponding to the frequency difference from 0.10 to 14 THz, which is the largest tuning range by the utilization of single device and hence providing a new opportunity towards the generation of CW THz radiation.

18.
Nanomaterials (Basel) ; 8(9)2018 Sep 10.
Article in English | MEDLINE | ID: mdl-30201917

ABSTRACT

As important functional materials, the electronic structure and physical properties of (GaAs)m(AlAs)n superlattices (SLs) have been extensively studied. However, due to limitations of computational methods and computational resources, it is sometimes difficult to thoroughly understand how and why the modification of their structural parameters affects their electronic structure and physical properties. In this article, a high-throughput study based on density functional theory calculations has been carried out to obtain detailed information and to further provide the underlying intrinsic mechanisms. The band gap variations of (GaAs)m(AlAs)n superlattices have been systematically investigated and summarized. They are very consistent with the available reported experimental measurements. Furthermore, the direct-to-indirect-gap transition of (GaAs)m(AlAs)n superlattices has been predicted and explained. For certain thicknesses of the GaAs well (m), the band gap value of (GaAs)m(AlAs)n SLs exponentially increases (increasing n), while for certain thicknesses of the AlAs barrier (n), the band gap value of (GaAs)m(AlAs)n SLs exponentially decreases (increasing m). In both cases, the band gap values converge to certain values. Furthermore, owing to the energy eigenvalues at different k-points showing different variation trends, (GaAs)m(AlAs)n SLs transform from a Γ-Γ direct band gap to Γ-M indirect band gap when the AlAs barrier is thick enough. The intrinsic reason for these variations is that the contributions and positions of the electronic states of the GaAs well and the AlAs barrier change under altered thickness conditions. Moreover, we have found that the binding energy can be used as a detector to estimate the band gap value in the design of (GaAs)m(AlAs)n devices. Our findings are useful for the design of novel (GaAs)m(AlAs)n superlattices-based optoelectronic devices.

19.
Huan Jing Ke Xue ; 39(3): 997-1003, 2018 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-29965442

ABSTRACT

Under a condition of good air quality (AQI:55-90, PM10:37-97 µg·m-3, PM2.5:17-76 µg·m-3), six groups of 54 samples were collected using an Andersen cascade impactor from both the indoor and outdoor stations in Beijing and Xinxiang from June to August in 2016. The samples were digested by microwave digestion, and nine heavy metal elements (Pb, Cr, Ni, Cu, Zn, As, Cd, Mn, and Co) in the atmospheric particles were determined with an inductively coupled plasma source mass spectrometer (ICP-MS). The results showed that the enrichment index (0-3) of most elements were low in both cities except for Cd[15.0 (Beijing) and 8.47 (Xinxiang)]. Cr, Co, Cu, and Mn in the atmospheric particles from Beijing park, Cd, Pb, and Mn in the atmospheric particles from the Beijing office, Cr, Co, Ni, and As in the atmospheric particles from Xinxiang park, and all nine heavy metal elements in the atmospheric particles from roads in both cities were found to be more concentrated in the coarse fractions; however, Pb, Zn, Cd, Ni, and As in the atmospheric particles from Beijing park, Co, Zn, Ni, Cr, As, and Cu in the atmospheric particles from the Beijing office, Pb, Zn, Cd, Cu, and Mn in the atmospheric particles from Xinxiang park, and all nine metal elements in the atmospheric particles from the Beijing office showed the opposite pattern. The result of a human health risk assessment indicated that the carcinogenic risk of the five carcinogenic elements were all less than 10-4, but a lower potential cancer risk would also occur under long term exposure. For the four non-carcinogenic elements (Pb, Zn, Mn, and Cu), the non-carcinogenic health risk values of Pb, Zn, Mn, and Cu in the atmospheric particulates in Beijing were all far less than 1, which means the corresponding non-carcinogenic risk was negligible; and, except for Mn, there was no obvious non-carcinogenic risk from Pb, Zn, and Cu in the atmospheric particles of Xinxiang.


Subject(s)
Air Pollutants/analysis , Metals, Heavy/analysis , Beijing , Cities , Environmental Monitoring , Humans , Particle Size , Risk Assessment
20.
Neuropharmacology ; 137: 104-113, 2018 07 15.
Article in English | MEDLINE | ID: mdl-29758384

ABSTRACT

Src-homology 2 domain-containing protein tyrosine phosphatase-1 (SHP1) is one of the non-receptor-like phosphatases that are highly enriched in hematopoietic cells. Although accumulating evidence has implicated the protein tyrosine phosphatases in the regulation of nociceptive transmission and plasticity, it is largely unknown whether SHP1 was expressed in pain-related spinal cord dorsal horn and engaged in the synaptic modification of nociceptive signals. Here we found that SHP1 was present in spinal neurons of rats and functionally coupled to GluN2A subunit-containing N-methyl-d-aspartate subtype of glutamate receptors, one of the key players in central sensitization of nociceptive behaviors. SHP1 interacted with a membrane-proximal region within the cytoplasmic tail of GluN2A. This interaction was necessary to stimulate SHP1 activity and more importantly, restrict SHP1 signaling to specifically enhance the tyrosine phosphorylation of GluN2A during inflammatory pain. Electrophysiological and behavioral studies showed that SHP1 binding potentiated GluN2A currents and evoked GluN2A-dependent pain hypersensitivity. The siRNA-mediated knockdown of SHP1 or interference with SHP1/GluN2A interaction by a synthetic peptide alleviated inflammatory pain induced by either Complete Freund's Adjuvant or formalin. Our data implicated that SHP1 was a specific enhancer of GluN2A-mediated nociceptive synaptic transmission in spinal cord dorsal horn, and manipulation of SHP1 activity may serve as an effective strategy for the treatment of inflammatory pain.


Subject(s)
Inflammation/metabolism , Pain/metabolism , Posterior Horn Cells/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Synaptic Transmission/physiology , Analgesics, Non-Narcotic/pharmacology , Animals , Gene Knockdown Techniques , HEK293 Cells , Humans , Inflammation/drug therapy , Male , Pain/drug therapy , Posterior Horn Cells/drug effects , Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/physiology , Synaptic Transmission/drug effects , Tissue Culture Techniques , src-Family Kinases/metabolism
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