DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson’s disease

DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has shown recent potential as a treatment for Parkinson’s disease.However,the underlying mechanism of action of NBP remains poorly understood.In this study,we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days,followed by intragastric injection of NBP for 14-28 days.We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease,inhibited loss of dopaminergic neurons and aggregation ofα-synuclein,and reduced iron deposition in the substantia nigra and iron content in serum.These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor,ferritin light chain,and transferrin 1.NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease.Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition,oxidative stress,and ferroptosis in the substantia nigra.

Detection of hepatitis C virus core antigen for early diagnosis of hepatitis C virus infection in plasma donor in China

AIM： To evaluate the efficacy of a new hepatitis C virus （HCV） core antigen assay developed in China. METHODS： After the determination of HCV infection, 49 serial samples were selected from II regular plasma donors in 5 different plasma stations. To compare the performance of HCV core antigen detection and HCV PCR, these samples were genotyped, and each specimen was analyzed by ELISA for the detection of HCV core antigen and by qualitative HCV PCR. RESULTS： Among all of the sequential samples, the original 23 specimens were HCV RNA-negative, and 36 samples were HCV RNA-positive. Twenty-seven samples （75%） were HCV core antigen-positive from these HCV RNA-positive specimens. Conversely, 27 samples （93.2%） were found HCV RNA-positive in HCV core antigen- positive samples. Intervals between HCV RNA and HCV core antigen-positive, as well as between HCV core antigen-positive and HCV antibody-positive were 36.0 and 32.8 d, respectively. CONCLUSION： This HCV core antigen assay, developed in China, is able to detect much of anti-HCV-negative, HCV RNA-positive preseroconversion window period （PWP） plasma donations.

Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis,Synaptic Plasticity,and Cognitive Behavior in Mice

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit(EZH2)-mediated trimethylation of histone H3 lysine 27(H3K27me3)regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system.Here,we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line.The results showed that a lack of neuronal EZH2 led to delayed neuronal migration,more complex dendritic arborization,and increased dendritic spine density.Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis.In particular,the gene encoding p21-activated kinase 3(Pak3)was identified as a target gene suppressed by EZH2 and H3K27me3,and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density.Finally,the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice.Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development,and has long-lasting effects on cognitive function in adult mice.

Volatilization behaviour and volatilization kinetics of CaF2-Na2O-CaOSiO2-Al2O3-MgO-B2O3 synthetic mould flux

To reduce the volatilization of the volatile-containing slags and obtain accurate measurement results of slag performance,the volatility degree and deviation mechanism must be determined.Non-isothermal thermogravimetric analysis at different heating rates was used to establish the volatilization kinetic model,and it reveals the volatilization mechanism of CaF2-Na2O-CaO-SiO2-Al2O3-MgO-B2O3 synthetic sodium-containing fluoride mould flux.The results demonstrated that the evaporation of NaF and SiF4 was the decisive factor that led to the change in composition and deviation of properties of the tested slags.The most probable kinetic mechanism function for the evaporation of volatile component from sodiumcontaining fluoride mould flux could be expressed by g(α)=[—ln(1-α)]^2/3,with an apparent activation energy of 164.866 kJ mol^-1 and pre-exponential factor of 2.13×10^-4 s^-1,where α is the conversion rate at any time step in the volatilization process.The reaction mechanism was random nucleation followed by growth,which was the limiting factor for the volatilization of synthetic sodium-containing fluoride mould flux.The method of increasing heating rate and adding protection gas in the measurement system will help to obtain more accurate results of slag performance.

Escitalopram with or without combined electroacupuncture on protracted alcohol withdrawal symptoms(PAWS)among male inpatients with alcohol dependence

Objective:This study is conducted to investigate the effects differences of escitalopram with or without combined electroacupuncture(EA)among male inpatients with a diagnosis of alcohol dependence and comorbid protracted alcohol withdrawal symptoms(PAWS).Methods:A total of 62 participants who met the inclusion criteria were enrolled in a two-arm randomized,placebo controlled,patients-blind trial and allocated to an escitalopram with real-EA group(realEA group,patients=31)and an escitalopram with sham-EA group(sham-EA group,patients=31),respectively.In addition to the oral administration of escitalopram for total four weeks,patients in each group received corresponding EA treatment five days per week and two days off for consecutive four weeks.Both serum homocysteine(Hcy)test and electrophysiological tests,including event-related potentials(ERPs)and exploratory eye movement(EEM)were performed at pre-and post-treatment.Additionally,the global scores of Penn Alcohol Craving Scale(PACS),17-items Hamilton Depression Rating Scale(HAMD-17),and Hamilton Anxiety Scale(HAMA)were used for assessing the subjective emotion experience of patients,respectively.Meanwhile,adverse effects were monitored and recorded.Results:After four-week treatment,the global scores of PACS and HAMD-17 declined significantly in both groups(both P<0.05).Furthermore,the decline in the real-EA group was superior to that in the shamEA group(P<0.05).Meanwhile,the total scores of HAMA only decreased in the real-EA group(P<0.05)but not in the sham-EA group(P>0.05).According to the parameters of ERPs,significant declines for N2PL,P3PL,and P3amp were observed in both two groups(all P<0.05),and the decreases for P3PL and P3amp in the real-EA group was much superior to that in the sham-EA group(both P<0.05).According to the parameters of EEM,significant increase for NEF was observed only in the real-EA group(P<0.05).Besides,there was a dramatic decline for serum Hcy level only in the real-EA group(P<0.05).One case in the sham-EA group withdrew from the trial due to self-reported nausea and bitter taste,and outcomes of the remaining 61 patients were adopted for analysis.Conclusion:(1)Escitalopram with EA may be a potential alternative therapy for mitigating PAWS among male inpatients with alcohol dependence.(2)Escitalopram with EA might improve the alcoholdependence induced cognitive dysfunctions via upregulating the expression of Hcy.

Novel glycine-dependent inactivation of NMDA receptors in cultured hippocampal neurons

Objective Glycine acts as a co-agonist for the activation of N-methyl-D-aspartate receptors （NMDARs） by binding to glycine sites, thus potentiating glutamate-elicited responses and inhibiting NMDAR desensitization in a dose-dependent manner. The present study aimed to characterize the glycine-dependent inactivation of NMDARs and to explore its pathophysiological significance. Methods Primary hippocampal cell cultures from embryonic days 17-18 rats were treated with NMDA or NMDA plus glycine. Patch-clamp recording and intracellular Ca 2＋ imaging were performed to test the effects of glycine on NMDA-activated currents and increase of intracellular free Ca 2＋ respectively. Immunofluorescence staining was conducted to examine NR1 internalization. Cell damage was tested with MTT method and lactate dehydrogenase leakage. Results Glycine reduced the peak current and Ca 2＋ influx elicited by NMDA application at concentrations ≥300 μmol/L. This is a novel suppressive influence of glycine on NMDAR function, since it occurs via the NMDAR glycine-binding site, in contrast to the classic suppression, which occurs through the binding of glycine to glycine receptors. The level of membrane NMDARs was measured to evaluate whether internalization was involved. Immunohistochemical labeling showed that incubation with high concentrations of NMDA plus glycine did not change the expression of NMDARs on the cell surface when compared to the expression without glycine; hence the possibility of NMDAR internalization primed by glycine binding was excluded. Conclusion In summary, the novel suppressive effect of glycine on NMDARs was mediated via binding to the glycine site of the NMDAR and not by activation of the strychnine-sensitive glycine-receptor-gated chloride channel or by the internalization of NMDARs. The inhibitory influence of glycine on NMDARs adds a new insight to our knowledge of the complexity of synaptic transmission.

Experimental study on the origin of lobe-cleft structures in a sand storm

Lobes and clefts are characteristic structures at the front of sand storms.In this paper,their original formation mechanism and geometric features are studied experimentally and theoretically.A rotatable lock-exchange tank is utilized to avoid the strong local disturbances existing in the conventional horizontal apparatus,and the original lobe size is selected as the dominant spanwise wavelength by a statistical method instead of the mean lobe size used in the literature.It is shown that at the initial formation stage,the measured lobe sizes for different tank geometries and density differences(or Atwood numbers)have a 1/3 scaling law with the Grashof number(Gr)as predicted by a Rayleigh-Taylor(RT)model,especially at moderate Gr range,and substantially depend on the diffusion effect represented by the Schmidt number.Furthermore,using turbulent Schmidt number and eddy viscosity for atmosphere in the RT model predicts large scale dominant lobes,whose sizes agree qualitatively with those observed in a real sand storm,revealing that the underlying control mechanism for these lobe and cleft structures is intrinsically related to the RT instability.

ESL-SELO:A Robust Image Denoising Algorithm with Penalty

Robust image recovery methods have been attracted more and more attention in recent decades for its good property of tolerating system errors or measuring noise. In this paper, we propose a new robust method （ESL-SELO） to recover nosing image, which combine exponential loss function and seamless-L0 （SELO） penalty function to guarantee both accuracy and robustness of the estimator. Theoretical result showed that our method has a local optimal solution and good asymptotic properties. Finally, we compare our method with other methods in simulation which shows better robustness and takes much less time.

Does acupuncture response increase with the increasing dosage:A preclinical study investigating rats with sleep deprivation

Background:The effectiveness of acupuncture for insomnia and insomnia-related anxiety and depression has been widely investigated in clinical trials.However,whether higher dosage(more frequent)acupuncture can bring greater responses(a greater size of effect)is less understood.Objective:This study is designed to investigate whether a five-times weekly(5 Ts/w)electroacupuncture(EA)treatment is better than a three-times weekly(3 Ts/w)EA in alleviating sleep deprivation,and sleep disturbance-induced cognitive dysfunctions and negative emotions in rats through four various behavioral te sts.Methods:Forty-six male Sprague-Dawley rats were randomly divided into control group(n=10),model group(n=12),EA-3 Ts/w group(n=12),and EA-5 Ts/w group(n=12).Except for the control group,the other three groups were established as chronic sleep deprivation models via the modified multi-platform water environment methodology.Then,rats in both EA-3 Ts/w group and EA-5 Ts/w group received corresponding dosage of EA therapy,respectively.After modeling and interventions,all four groups received four behavioral tests as follows:(1)sleep behavioral monitoring and evaluation was achieved by Comprehensive Lab Animal Monitoring System(CLAMS).(2)Cognitive functions were assessed by Novel Object Recognition(NOR)test.(3)Depressive-like behaviors was evaluated by Open-Field(OF)test.(4)Anxietylike behaviors was appraised by Elevated Plus-Maze(EPM)test.After finishing the behavioral tests,the hippocampus of each rat was removed and its synaptic structure changes were observed under electron microscope.Results:(1)CLAMS:two EA groups derived more sleep time within 24 h than the model group(both P<0.05),and no statistical differences was found between these two EA groups(P>0.05).(2)NOR test:NOR ratio in the EA-3 Ts/w group was higher than that of the model group(P<0.05)but lower than that of either the control group(P<0.05)or the EA-5 Ts/w group(P<0.05).(3)OF test:the difference of horizontal movements between the EA-3 Ts/w group and the EA-5 Ts/w group was not significant(P>0.05),although both of them were lower than that of the control group(both P<0.05)but higher than that of the model group(P<0.05).(4)EPM test:no significant decline of open-arm total time(OT)was found in EA-3 Ts/w group(P>0.05)but was found in both the model group(P<0.05)and the EA-5 Ts/w group(P<0.05)compared to the control group.Conclusion:(1)Five-week EA treatment can partially mitigate cognitive dysfunctions,anxiety-like behaviors,and depressive behaviors in rats with sleep deprivation,and this effect might be associated with the repairs on mitochondrial damage in hippocampal neurons.(2)There is insufficient evidence supporting 3 Ts/w EA treatment is less effective than 5 Ts/w EA treatment in mitigating sleep deprivation symptoms and depressive behaviors induced by sleep deprivation among rats.(3)5 Ts/w EA treatment might be more effective than 3 Ts/w EA treatment in attenuating sleep deprivation-induced cognitive impairments while it might further increase rat’s anxiety-like behaviors at the same time.

Simultaneous Determination of Four Substances in Plasma and Dermal Microdialysates of Guinea Pig after Different Acupoints Administration of Fufang Baijiezi Gel

Objective To study the pharmacokinetic properties of Fufang Baijiezi Gel（FBG） after different acupoints administration. Methods Sinapine thiocyanate, tetrahydropalmatine, 6-gingerol, and asarinin, which were four substances of FBG, were determined by a sensitive liquid chromatography tandem mass spectrometry method（LC-MS） both in plasma and dermal microdialysates of guinea pig simultaneously. Microdialysates were separated on an Ultimate？ XB-Phenyl analytical column（150 mm ×2.1 mm, 5μm） and detected by electrospray ionization（ESI） in selected ion monitoring（SIM） mode. The method was validated in terms of selectivity, linearity, sensitivity, and recovery. Result A significant difference was observed in main pharmacokinetic parameters of C max, t max, and AUC between acupoints administration and nonacupoints administration. Conclusion Acupoints administration resulted in a more obvious increase in bioavailability of sinapine thiocyanate, tetrahydropalmatine, 6-gingerol, and asarinin than nonacupoints administration.

Erratum to： Novel glycine-dependent inactivation of NMDA receptors in cultured hippocampal neurons

Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2013