Correlation Analysis of Molecularly-Defined Cortical Interneuron Populations with Morpho-Electric Properties in Layer V of Mouse Neocortex / 神经科学通报·英文版

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.

O-GlcNAcylation in Ventral Tegmental Area Dopaminergic Neurons Regulates Motor Learning and the Response to Natural Reward / 神经科学通报·英文版

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.

Growth Differentiation Factor-15 Produces Analgesia by Inhibiting Tetrodotoxin-Resistant Nav1.8 Sodium Channel Activity in Rat Primary Sensory Neurons / 神经科学通报·英文版

Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.

Growth Differentiation Factor-15 Produces Analgesia by Inhibiting Tetrodotoxin-Resistant Nav1.8 Sodium Channel Activity in Rat Primary Sensory Neurons / 神经科学通报·英文版

Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.

Study on metabolites from a sponge-derived fungus / 中国中药杂志

We have carried out the investigation on a sponge-derived fungus,which was identified as Emericella variecolor from the south sea of China. Two new chemical constituents,(+)-2-acetyl-dihydroterrein (1) and (+)-3-acetyl-dihydroterrein (2),with four known compounds,anditomin (3),andilesin A (4),andilesin C (5) and andilesin B (6),were isolated from this fungus by column chromatography over silica gel, Sephadex LH-20, and ODS. The structures of 1 and 2 were elucidated by spectroscopic methods including NMR,HR-ESI-MS,and CD.

Terpenoids from Euphorbia micractina / 药学学报

From an ethanol extract of Euphorbia micractina roots, sixteen terpenoids were isolated by a combination of various chromatographic techniques, including column chromatography over macroporous resin, silica gel, and Sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by spectroscopic data analysis as loliolide myristate (1), 24-methylenetirucall-8-en-3β,11α-diol-7-one (2), loliolide (3), 3β-hydroxy-5α,6α-epoxy-7-megastigmen-9-one (4), jolkinol A (5), jolkinol D (6), latilagascene F (7), helioscopinolide A (8), helioscopinolide B (9), 3-O-acetylhelioscopinolide B (10), helioscopinolide D (11), helioscopinolide E (12), (+)-11-acetoxyatis-16-en-3,14-dione (13), erythrodiol (14), uvaol (15) and betulin (16). All of the compounds were obtained from this plant for the first time, in which 1 and 2 are new compounds.

Steroids and aromatic derivatives from Euphorbia micractina / 中国中药杂志

From an ethanol extract of Euphorbia micractina roots, seven steroids fifteen aromatic derivatives were isolated by a combination of various chromatographic techniques, including column chromatography over macroporous resin, silica gel, and Sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by spectroscopic data analysis as stigamast-5-ene-3beta, 7alpha-diol(1), stigamast-5-ene-3beta,7beta-diol(2), stigmast-5-en-3beta-ol-7-one(3), stigmast-4-en-6beta-ol-3-one(4), stigmast-1, 4-dien-3-one(5), stigmast-3,6-dione(6), beta-sitosterol(7), scopoletin(8), aesculetin(9), 6-hydroxy-5,7-dimethoxycoumarin(10), quercetin(11), 3,3', 4'-tri-O-methylellagic acid(12), p-hydroxyphenylethyl anisate(13), m-hydroxyphenylethyl alcohol(14), (E)-cinnamic acid(15), (E)-ferulic acid(16), 3,4-dihydroxybenzoic acid(17), vanillic acid(18), p-hydroxybenzoic acid(19), ethyl 3,4-dihydroxybenzoate (20), ethyl gallate(21), and methyl gallate(22). These compounds were obtained from this plant for the first time.

Glycosides from Machilus wangchiana / 中国中药杂志

Ten glycosidic compounds were isolated from an ethanol extract of Machilus wangchiana by a combination of various chromatographic techniques including column chromatography over silica gel and Sephadex LH-20 and reversed-phase flash chromatography and HPLC. Their structures were identified by spectroscopic data analysis (IR, MS, and NMR) as icariside B1 (1), boscialin-3-O-β-D-glucopyranoside (2), pisumionoside (3), isolariciresinol-9'-O-β-D-xylopyranoside (4), 5'-methoxyisolariciresinol-9'-O-β-D-xylopyranoside (5), lyoniresinol-9'-O-β-D-xylopyranoside (6), (E) -4-hydroxyphenylprop-7-ene 4-O-β-D-glucopyranoside (7), (E) - 4-hydroxy-3-methoxyphenylprop-7-ene 4-O-α-L-rhamnopyranosyl-(1 --> 6) -β-D-glucopyranoside (8), 4-hydroxy-3-methoxyphenylprop-8-ene 4-O-β-D-xylopyraosyl-(1 --> 6) -β-D-glucopyranoside (9), and 4-hydroxy-3,5-dimethoxyphenylprop-8-ene 4-O-α-L-rhamnpyranosyl-(1 --> 6)-β-D- glucopyranoside (10), respectively.

Mechanical analysis on laparoscopic instruments when contacting with biological tissues / 医用生物力学

Objective To establish the contact deformation model of biological tissues contacting with endoscopic instruments, and to make mechanical analysis on contact stress and strain. Methods Based on Kelvin-Voigt model and Hertz contact theory, the contact deformation model of instruments (with both wedge-shaped teeth and cylinder-shaped teeth) contacting with biological tissues was established, and the variation of contact stress and strain changing with time in different endoscopic instruments were obtained through finite element analysis method and bio-impedance measurement. Results Endoscopic instruments with different structures of the teeth could cause different strain and stress on tissues during laparoscopic grasping. The stress of the instrument with wedge-shaped teeth on tissues was largest, while that with cylinder-shaped teeth was smallest, and that of instrument with hybrid structure of wedge-shaped and cylinder-shaped teeth was in between. Conclusions The hybrid structure of wedge-shaped and cylinder-shaped teeth can effectively reduce the peak pressure during laparoscopic grasping, thus prevent less tissue damage caused by wedge-shaped teeth, and enhance the grasping ability with cylinder-shaped teeth. This study provides an important reference for the safety use and better design of laparoscopic instruments in clinic.

Flavonoids from root of Machilus wangchiana / 中国中药杂志

Twelve flavonoids were isolated from an ethanol extract of Machilus wangchiana by a combination of various chromatographic techniques including column chromatography over silica gel and Sephadex LH-20 and reversed-phase flash chromatography and HPLC. Their structures were identified by spectroscopic data analysis (IR, MS, and NMR) as (+)-catechin (1), (-)-epicatechin (2), 3'-O-methyl-(+)-catechin (3), 3'-O-methyl-(-)-epicatechin (4), 3, 5, 7, 2', 5'-pentahydroxy flavan (5), (-)-naringenin (6), (-)-eriodictyol (7), (-)-liquiritigenin (8), (2R,3R)-(+)-dihydrokaempferol (9), (2R,3S)-(-)-dihydro- kaempferol (10), (2R, 3R)-(+)-taxifolin (11), and quercetin (12). Compounds 1-10 are isolated from the genus Machilus for the first time.

The contralateral C_7 transfer via prespinal route to repair the brachial plexus avulsion:A preliminary study on its clinical effect / 中华显微外科杂志

Objective To investigate a shorter and safer route for contralateral C_7 nerve root transfer. Methods Eight male patients were treated from Dec2005 to Nov.2006Their range of age was from 22 to 43 years with an average of 30 yearsFive cases had total brachial plexus avulsion.The operative delay was from 2 to 6 months(mean:4 months).The sealenus anterior muscle was transected before a prespinaJ & ret- ropharyngeal tunnel was madeThe contralateral C_7 nerve root was used to repair the upper trunk or the infra- clavicular lateral cord and posterior cord of injured side via this routeusing direct anastomosis or nerve graft- ing.Results The length of the harvested contralateral C_7 nerve root was(4.67?0.52em in the early 5 casesThe nerve graft was6.25?0.35)em long for repairing supraclavicular brachial plexus and(8.56?0.45cm long for repairing infraclavicular brachial plexusThe length of the harvested contralateral C_7 nerve root averaged 6.85cm in the other 3 cases2 of which had direct anastomosis to the residual nerve C_5 and C_6 nerve roots and the other used nerve graft of 3 cm in lengthTransient contralateral sensory symptoms were re- ported in most patientsAt 3 months followups6 patients had tingling sensation on the contralateral fingers with percussion on the injured cervical areaIpsilateral SSEP could be recorded by stimulating at 2 cm above sternoclavicular joint on the injured sideAt 7 months follow ups of 5 patientsCMAP could be recorded in bi- cepsdeltoids and infraspinatus or triceps with stimulation at Erb's pointHoweverno clinical movements was noticedAt 12 months follow ups of 3 patientswe could observe early motor and sensory function recovery of those patients to different extent.Conclusion Transection of anterior scalenus muscle shortens the length of the transfer route and allows more efficient neurotizationThe procedure is convenient and safeprovided certain precautions being usedThe principal of contralateral C_7 nerve transfer are reconstruct the anterior divi- sions of upper trunkposterior divisions of upper trunk and suprascapular nerve when repairing the supraclavic- ula brachial plexusReconstruct the lateral cord and posterior cord when repairing the infraclavicula brachial plexusPostsurgical fasting for 4 days included foods and liquids will benefit of healing of anastomosed nerves and regenerationaud avoid complications.