Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist inhibits apoptosis of retinal ganglion cells in a rabbit model of optic nerve injury

A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist GYKI 52466 on apoptosis of retinal ganglion cells following nerve injury. Hematoxylin-eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that retinal ganglion cells gradually decreased with increasing time of optic nerve injury, while GYKI 52466 could inhibit this process. The results demonstrate that following acute optic nerve injury, apoptosis of retinal ganglion cells is a programmed process, which can be inhibited by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist.

Synthesis,Crystal Structure,and Magnetic Property of One 3D Nickel Coordination Polymer Based on 2-Hydroxy-5-(3',5'-terephthalic acid)Pyridine and 1,4-Bis(1-imdazoly)benzene

One novel nickel coordination polymer, {[Ni（OTP）（bib）1.5（H2O）]·2H2O}n（1, H2 OTP = 2-hydroxy-5-（3＇,5＇-terephthalic acid） pyridine, bib = 1,4-bis（1-imdazoly）benzene）, has been synthesized and characterized by elemental analysis（EA）, IR, powder X-ray diffraction（PXRD）, and thermogravimetric（TG） analyses. The crystal of 1 crystallizes in monoclinic, space group P21/n with a = 12.2860（5）, b = 13.8246（6）, c = 19.0140（8） A, β = 104.3870（1）°, V = 3128.2（2） A3, Z = 4, C32H28N7 Ni O8, Mr = 697.32, Dc = 1.481 g/cm^3, F（000） = 1444 and μ（Mo Kα） = 0.684 mm-1. The final R = 0.0704 and w R = 0.1764 for 5485 observed reflections with I 2σ（I） and R = 0.1087 and wR = 0.2010 for all data. Topology analysis reveals that complex 1 is a 3D 2-fold interpenetrated {4^4·6^6}-nov net based on the 1D [Ni（OTP）]n chain and the 2D [Ni2（bib）3]n sql sheet. And the variable-temperature magnetic susceptibility measurements exhibit weak antiferromagnetic coupling interaction.

Microwave-assisted Polycondensation of L-2-Hydroxy-3-phenylpropanoic Acid

Amorphous poly (L-2-hydroxy-3-phenylpropanoic acid) (PLHPPA) was synthesized by the microwave-assisted polycondensation of L-2-hydroxy-3-phenylpropanoic acid (LHPPA). The weight average molar mass (Mw) of PLHPPA ranged from 3600 to 5300 and polydispersity index (Mw/Mn) from 1.0 to 1.4 when the reaction mixture was irradiated by microwave at 255, 340 and 510 w for 1 to 10 h, respectively.

Supramolecular complex formation of β-cyclodextrin polymer with substituted salicylic acid or 3-hydroxy-2-naphthoic acid and their electrorheological behaviors

According to the chemical design, electrorheological properties of supramolecular complex from b-cyclodextrin polymer (b -CDP) were discussed. Six supramolecular complexes of -cyclodextrin polymer with substituted salicylic acid and 3-hydroxy-2-naphthoic acid were syn-thesized by the solid-phase self-assembly method, and their component and structure were characterized by NMR, FT-IR, UV-vis and the fluorescence analysis. Then the electrorheological properties of their suspensions in silicone oil were investigated under DC electric fields. It was found that the yield stresses of these supramolecular complex ER fluids were 7.3—9.8 kPa at 4 kV/mm in DC electric field, which were enhanced by 34%—72% compared with that of pure b-CDP. Among them, that of b-CDP/3-hydroxy-2-naphthoic acid ER fluid was the highest. It was also found that the ER effect of supramolecular complexes can be controlled by changing dif-ferent guests. When the substituted group is at phenyl ring, ER behavior can be slightly adjusted by the different substituted groups, their number as well as their position at phenyl ring. This can be proved by the measurement of dielectric properties.

A New Sesquiterpene-substituted Benzoic Acid from the Brown Alga Dictyopteris divaricata

A new sesquiterpene-substituted benzoic acid has been isolated from the brown Alga Dictyopteris divaricata Okam.. Its structure was elucidated as 3-[(2-hydroxy-2,5,5,8a-tetra- methyldecahydro-1-naphthalenyl)methyl]-4-hydroxybenzoic acid, named dictyvaric acid on the basis of spectroscopic methods including IR, HRFABMS, 1D and 2D NMR techniques.

Alumina-supported heteropoly acid:An efficient catalyst for the synthesis of azaarene substituted 3-hydroxy-2-oxindole derivatives via C(sp^3)-H bond functionalization

A method of C（sp^3）-H bond functionalization of methyl azaarenes catalyzed by alumina-supported heteropoly acid and addition to isatins was developed. This transformation could be used for the synthesis of biologically important 3-hydroxy-2-oxindole derivatives in good to excellent yields and the catalyst could be reused for six times without significant decrease in activity.

枳椇子中甾类化合物的分离

从枳椇子Hovenia acerba中分离得到3个化合物,分别为β-谷甾醇(-βsitosterol)(Ⅰ);3β-Hydroxy-3-de-oxymoron ic ac id(Ⅱ)和胡萝卜苷(Ⅲ)。上述三个化合物均为自该属植物中首次获得。

Modified constraint-induced movement therapy alters synaptic plasticity of rat contralateral hippocampus following middle cerebral artery occlusion

Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb.However,the molecular mechanism underlying its efficacy remains unclear.In this study,a middle cerebral artery occlusion(MCAO)rat model was produced by the suture method.Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days,starting from the 7^th day after middle cerebral artery occlusion.Day 1 of treatment lasted for 10 minutes at 2r/min,day 2 for 20 minutes at 2 r/min,and from day 3 onward for 20 minutes at 4 r/min.CatWalk gait analysis,adhesive removal test,and Y-maze test were used to investigate motor function,sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21^st day after MCAO.On the 21^st day after MCAO,the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay.The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography.The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats,but had no effect on cognitive function.The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3(Gria3)in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1 A,Avprla in the middle cerebral artery-occluded rats.In the ipsilateral hippocampus,only Adra2 a was downregulated,and there was no significant change in Gria3.Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3,which is an a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor,within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region.The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged.Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion,but had no effect on Synapsin I levels.Besides,we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus.This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats,and suggests that these positive effects occur via the upregulation of the postsynaptic membrane a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression.This study was approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.

Indole Alkaloids from the Roots of Ervatamia hainanensis

Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy （2-oxopropyl）-methyl ester 2, were isolated from Ervatamia hainanensis. Their structures were elucidated on the basis of spectroscopic methods.

Binocular form deprivation influences the visual cortex

a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are considered to play a crucial role in synaptic plasticity in the developing visual cortex. In this study, we established a rat model of binocular form deprivation by suturing the rat binocular eyelids before eye-opening at postnatal day 14. During development, the decay time of excitatory postsynaptic currents mediated by a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors of normal rats became longer after eye- opening; however, the decay time did not change significantly in binocular form deprivation rats. The peak value in the normal group became gradually larger with age, but there was no significant change in the binocular form deprivation group. These findings indicate that binocular form deprivation influences the properties of excitatory postsynaptic currents mediated by a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat visual cortex around the end of the critical period, indicating that form stimulation is associated with the experience-dependent modification of neuronal synapses in the visual cortex.

Genetic variables of the glutamatergic system associated with treatment-resistant depression:A review of the literature

Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.

壮药龙脷叶化学成分研究(Ⅱ)

目的研究壮药龙脷叶Sauropusrostratus的化学成分。方法通过硅胶、聚酰胺、MCI、凝胶等柱色谱及重结晶方法进行分离和纯化，根据理化性质和波谱数据对化合物结构进行鉴定。结果从龙脷叶75％乙醇提取物中分离得到19个化合物，分别鉴定为正三十烷醇（1）、2,4-二叔丁基苯酚（2）、3-谷甾醇（3）、胡萝卜苷（4）、3,6．anhydro-2-deoxy-D-arabino-hexono-l，4-lactone（5）、烟酰胺（6）、东莨菪亭（7）、3β-hydroxy-26α，27β-arbor-13（18）-ene-24-carboxylicacid（8）、2R＊，3R＊，5S＊-tnhydroxy-6R＊-nonadecyltetrahydropyran-4-one（9）、大黄素（10）、原儿茶酸（11）、2，3-dideoxy-D-erythro-hex-2-enono-1，4-lactone（12）、咖啡酸（13）、3-乙酰氧基咖啡酸（14）、槲皮素（15）、D-半乳糖（16）、甘露醇（17）、橙黄胡椒酰胺（18）、山柰酚（19）。结论化合物8为新化合物，命名为龙劂叶酸；化合物2、5-14、16-18均为首次从该属植物中分离得到。

羊耳蒜化学成分的研究

目的研究羊耳蒜(Liparis japonica)全草的化学成分。方法采用硅胶、ODS、Sephadex LH-20等柱色谱进行分离纯化,通过波谱学方法及与文献对照鉴定化合物结构。结果分离得到18个化合物,分别鉴定为acortatarin A(1),3β-hydroxy-5α,8α-epidioxyergosta-6,22-diene(2),13-epicupressic acid(3),3β-hydroxyolean-12-en-28-oic acid(4),白桦脂酸(5),gigantol(6),(2S)-3-O-octadeca-9Z,12Z,15Z-trienoylglyceryl-O-β-D-galactopyranoside(7),α-linolenic acid(8),hydroxydihydrobovolide(5-hydroxyl-3,4-dimethy-5-penty-12(5H)-furanone)(9),反式对羟基肉桂酸(10),(+)-丁香脂素(11),β-谷甾醇(12),2,5-二羟基-4-甲氧基-9,10-二氢菲(13),2,7-二羟基-3,4-二甲氧基菲(14),moscatin(15),山药素Ⅲ(16),亚油酸(17)和对羟基苯甲醛(18)。结论本实验首次从羊耳蒜属植物中分离得到结构独特的含吗啉片段的螺环生物碱,化合物2~11为首次从该属植物中分离得到。

A Role for Transmembrane Protein 16C/Slack Impairment in Excitatory Nociceptive Synaptic Plasticity in the Pathogenesis of Remifentanil-induced Hyperalgesia in Rats

Remifentanil is widely used to control intraoperative pain. However, its analgesic effect is limited by the generation of postoperative hyperalgesia. In this study, we investigated whether the impairment of transmembrane protein 16C(TMEM16C)/Slack is required for a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor(AMPAR) activation in remifentanil-induced postoperative hyperalgesia. Remifentanil anesthesia reduced the paw withdrawal threshold from 2 h to 48 h postoperatively,with a decrease in the expression of TMEM16C and Slack in the dorsal root ganglia(DRG) and spinal cord.Knockdown of TMEM16C in the DRG reduced the expression of Slack and elevated the basal peripheral sensitivity and AMPAR expression and function. Overexpression of TMEM16C in the DRG impaired remifentanilinduced ERK1/2 phosphorylation and behavioral hyperalgesia. AMPAR-mediated current and neuronal excitability were downregulated by TMEM16C overexpression in the spinal cord. Taken together, these findings suggest that TMEM16C/Slack regulation of excitatory synaptic plasticity via GluA1-containing AMPARs is critical in the pathogenesis of remifentanil-induced postoperative hyperalgesia in rats.

Fe-catalyzed regioselective Friedel–Crafts hydroxyalkylation of N-substituted glyoxylamide with indoles

An efficient regioselective Friedel-Crafts hydroxyalkylation of N-substituted glyoxylamide with various indoles catalyzed by Lewis acids was developed. The reactions proceeded smoothly at room temperature and the 2-hydroxy-2-（1H-indol-3-yl）-N-substituted acetamide resulted from the reactions catalyzed by FeSO4 were synthesized in excellent yields （up to 93%）. While the bisindole compounds were obtained when FeCl3 was used as a catalyst in excellent yields （up to 92%）. A possible mechanism was proposed.

Effects of intracerebroventricular NMDA and non-NMDA receptor agonists or antagonists on general anesthesia of propofol in mice

The effects of intracerebroventricular(icv)agonists and antagonists of N-methyl-D-aspartate(NMDA)and alpha-amino-3-hydroxy–5-methyl-4-isoxazole-propionic acid(AMPA)receptors on the general anesthesia of propofol were studied.A total of 144 Kunming mice,male and female with body mass of(22P3)g,were used.Part One of the Experiment:a total of 104 Kunming mice,male and female,were randomly divided into 13 groups.Intracerebroventricular artificial cerebral fluid(aCSF)or different doses of NMDA,AMPA,MK-801 or NBQX was injected immediately after intravenously administered propofol 25 mg/kg and the recovery time following the loss of righting reflex(LORR)was recorded.Part Two of the Experiment:a total of 40 Kunming female mice were divided randomly into 5 groups and injected with icv aCSF or NMDA,AMPA,MK-801 or NBQX after intraperitoneally administered propofol 50 mg/kg.The pain threshold of the mice was then investigated by hot-plate test(HPPT).NMDA(0.05 or 0.075μg,icv)or AMPA(0.05μg,icv)exhibited no effects on the LORR,but NMDA(0.1μg,icv)or AMPA(0.075 or 0.1μg,icv)prolonged the LORR significantly compared with the aCSF group(P<0.05,P<0.01).The LORR of the 2μg MK-801 group had no changes,while those of the 4 or 8μg MK-801 groups were prolonged significantly.The LORR of the 0.5,2 or 4μg NBQX groups were all prolonged significantly.NMDA 0.05μg or AMPA 0.05μg decreased the pain threshold slightly but did not differ in effect compared with the aCSF group;2μg MK-801 or 0.5μg NBQX both increased the pain threshold significantly.Our results indicate that propofol produces general anesthesia partly through an interaction with brain NMDA and AMPA receptors in mice.