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Bupleurum chinense DC. (Chaihu) is a traditional Chinese medicine (TCM) used in the treatment of anxiety. But the anxiolytic mechanisms of bupleurum are still unclear. Therefore, this unknown is predicted by network pharmacology study with molecular docking in the present study. The components of bupleurum were obtained from the databases. Genes associated with components and disease were also provided by databases. Overlapping genes between components and disease were analyzed. The network of medicine-components-targets-disease was constructed, visualized, and analyzed. Protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG) and molecular docking were conducted to predict the potential mechanisms of bupleurum on anxiety. A total of 9 bioactive components derived from bupleurum with 80 target genes were involved in anxiety. Neurotransmitter receptor activity, G protein-coupled amine receptor activity, regulation of blood circulation, neuroactive ligand-receptor interaction, calcium signaling pathway and salivary secretion may play significant roles in the anxiolytic of bupleurum. Molecular docking implicated that ACHE and MAOA showed high affinity for stigmasterol. Based on network pharmacology study with molecular docking, multi-component-multi-target-multi-pathway action mode of bupleurum on anxiety was elaborated. Stigmasterol might be the core bioactive component, while ACHE and MAOA might be the core target genes in the pharmacological profile of bupleurum on anxiety.

Viral pneumonia (VP) is becoming a persistent and pervasive burden of disease. Traditional Chinese medicine Injections (TCMIs) have been proved effective in the treatment of patients with VP, which are now widely used in China. The evidence of TCMIs for VP is evolving rapidly. This study aims to assess the comparative efficacy and safety of TCMIs to provide more evidence and sights for the treatment selection of VP.Seven databases were searched from their inception up to 16 March 2022. Only randomized controlled trials (RCTs) are included to compare the efficacy and safety of antiviral TCMIs for the treatment of viral pneumonia. Clinical efficacy and rate of adverse events were considered as primary outcomes.A total of 76 RCTs with eight TCMIs comprising 7925 patients were included in the NMA. According to NMA, Reduning Injection combined with conventional antiviral drugs (CAD) produced superior effects in the effective outcomes and reduced the adverse event incidence rate of VP.This study indicated that TCMIs combined with CAD was more effective and safer than CAD monotherapy and compared different TCMIs therapies, which provided guidance and reference for the selection of clinical treatment medication.

Although there are various Conus species with publicly available transcriptome and proteome data, no genome assembly has been reported yet. Here, using Chinese tubular cone snail (C. betulinus) as a representative, we sequenced and assembled the first Conus genome with original identification of 133 genome-widely distributed conopeptide genes. After integration of our genomics, transcriptomics, and peptidomics data in the same species, we established a primary genetic central dogma of diverse conopeptides, assuming a rough number ratio of ~1:1:1:10s for the total genes: transcripts: proteins: post-translationally modified peptides. This ratio may be special for this worm-hunting Conus species, due to the high diversity of various Conus genomes and the big number ranges of conopeptide genes, transcripts, and peptides in previous reports of diverse Conus species. Only a fraction (45.9%) of the identified conotopeptide genes from our achieved genome assembly are transcribed with transcriptomic evidence, and few genes individually correspond to multiple transcripts possibly due to intraspecies or mutation-based variances. Variable peptide processing at the proteomic level, generating a big diversity of venom conopeptides with alternative cleavage sites, post-translational modifications, and N-/C-terminal truncations, may explain how the 133 genes and ~123 transcripts can generate thousands of conopeptides in the venom of individual C. betulinus. We also predicted many conopeptides with high stereostructural similarities to the putative analgesic ω-MVIIA, addiction therapy AuIB and insecticide ImI, suggesting that our current genome assembly for C. betulinus is a valuable genetic resource for high-throughput prediction and development of potential pharmaceuticals.

Post traumatic stress disorder (PTSD) is widely regarded as a stress-related and trauma disorder. The symptoms of PTSD are characterized as a spectrum of vulnerabilities after the exposure to an extremely traumatic stressor. Considering as one of complex mental disorders, little progress has been made toward its diagnostic biomarkers, despite the involvement of PTSD has been studied. Many studies into the underlying neurobiology of PTSD implicated the dysfunction of neurosteroids biosynthesis and neuorinflammatory processes. Translocator protein 18 kDa (TSPO) has been considered as one of the promising therapeutic biomarkers for neurological stress disorders (like PTSD, depression, anxiety, et al) without the benzodiazepine-like side effects. This protein participates in the formation of neurosteroids and modulation of neuroinflammation. The review outlines current knowledge involving the role of TSPO in the neuropathology of PTSD and the anti-PTSD-like effects of TSPO ligands.

About 350 million people worldwide suffered from depression, but less than half of the patients received effective and regular treatments. Traditional Chinese Medicine (TCM) such as pinellia has been proven effective for antidepressant treatment with fewer side effects. However, the exact mechanisms remain unclear. Herein, we use the methods of network pharmacology and molecular docking to analyze the effective monomer components of pinellia and reveal the involved signaling pathways to produce antidepressant effects. TCMSP, BATMAN-TCM, and TCMID databases were utilized to analyze the bioactive ingredients and target genes derived from pinellia via the screening the molecular weight (MW), oral bioavailability (OB), blood-brain barrier (BBB) and drug similarity (DL). OMIM, TTD, DisGeNET, GeneCards and DrugBank databases were used to obtain key genes of depression. Then, the networks of protein-protein interaction (PPI) and "medicine-ingredients-targets-pathways" were built. The target signaling pathways were enriched by GO and KEGG by using R language. Furthermore, bioactive ingredients binding of the targets were verified by molecular docking. Nine active monomer ingredients and 96 pivotal gene targets were selected from pinellia. 10,124 disease genes and 87 drug-disease intersecting genes were verified. GO analysis proposed that the receptor activity of neurotransmitter, postsynaptic neurotransmitter, G protein-coupled neurotransmitter, and acetylcholine through the postsynaptic membrane could be modulated by pinellia. KEGG pathway analysis revealed that pinellia influenced depression-related neural tissue interaction, cholinergic synapse, serotonin activated synapse and calcium signaling pathway. Besides, the reliability and accuracy of results obtained from the indirect network pharmacology were validated by molecular docking. The bioactive components of pinellia made significant antidepressant effects by regulating the key target genes/proteins in the pathophysiology of depression.

Paeoniflorin (PF) is one of the important active components in peony that are known to produce the neuroprotective effects. However, the involved cytoprotective factors on brain astrocytes are remain unclear. Translocator protein 18 kDa (TSPO) and its downstream neurosteroids biosynthesis play a significant role in cytoprotection. Based on these, the role of TSPO and neurosteroids biosynthesis in the cytoprotective effects of PF is evaluated. The astrocyte cells were cultured and AC-5216 (TSPO ligand) was selected as the positive control drug. The cytoprotective effects of PF and the levels of neurosteroids were quantified by water-soluble tetrazolium assay and enzyme linked immunosorbent assay, respectively. The cytoprotective activities of PF were relevant to neurosteroids (e.g. progsterone and allopregnanolone) biosynthesis, while these effects were totally blocked by PK11195, trilostane and finasteride, respectively. In summary, the cytoprotective effects of PF maybe mediated by TSPO and neurosteroids biosynthesis. The findings may provide the new insights into the cytoprotective effects of PF.

Post traumatic stress disorder (PTSD) is a mental health condition that has a debilitating effect on a person's quality of life and leads to a high socioeconomic burden. Licorice has been demonstrated to have neuroprotective and antidepressant-like effects, but little is known about its effects for the treatment of PTSD. The present study aimed to explore the potential of licorice for PTSD therapy using a network pharmacology approach with molecular docking studies. The compounds of licorice were obtained from databases with screening by absorption, distribution, metabolism and excretion (ADME) evaluation. Genes associated with compounds or PTSD were obtained from public databases, and the genes overlapping between licorice compounds and PTSD were compared by Venn diagram. A network of medicine-ingredients-targets-disease was constructed, visualized, and analyzed using cytoscape software. Protein-protein interactions, gene ontology, pathway enrichment and molecular docking were performed to evaluate the effect of licorice for the treatment of PTSD. 69 potential compounds were screened after ADME evaluation. A total of 81 compound-related genes and 566 PTSD-related genes were identified in the databases with 27 overlapping genes. Licorice compounds (e.g., medicarpin, 7-methoxy-2-methyl isoflavone, shinpterocarpin, formononetin, licochalcone a) and target proteins (e.g., ESR1, PTGS2, NOS2, and ADRB2) with high degree in the network were involved in G protein-coupled receptor signaling pathways at the postsynaptic/synaptic membrane. Moreover, neuroactive ligand-receptor interactions, calcium signaling, cholinergic synapse, serotonergic synapse and adrenergic signaling in cardiomyocytes may play important roles in the treatment of PTSD by licorice. This study provides molecular evidence of the beneficial effects of licorice for the treatment of PTSD.

Post-traumatic stress disorder (PTSD) is the serious psychiatric disorder. Paeoniflorin (PF) produces the antidepressant-like properties. However, few studies are concerned about its anti-PTSD-like effects and mechanisms. To investigate these, the single prolonged stress (SPS) model was utilized. PTSD-like behavioral deficits in rats after exposure to SPS were improved by PF (10 and 20 mg/kg, i.p.), evidenced by blocking increased freezing time in contextual fear paradigm (CFP) and increased time and entries in open arms in elevated plus maze (EPM) test without affecting the locomotor activity in open field (OF) test. We also found that increased levels of corticosterone (Cort), corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) after exposure to SPS were reversed by PF (10 and 20 mg/kg, i.p.) in serum, respectively. Moreover, the decreased levels of serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus were reversed by PF (10 and 20 mg/kg, i.p.), respectively. In summary, the anti-PTSD-like activities of PF were associated with the modulation of HPA axis and 5-HT system activation.

Anxiety disorder is a serious and burdensome psychiatric illness that frequently turn into chronic clinical conditions. Puerarin have been shown to be effective in the therapy of depression. However, few studies are concerned about the anxiolytic-like effects of puerarin. The current study aimed to evaluate the anxiolytic-like effects of puerarin and its possible mechanism. To evaluate this, the behavioral tests, i.e. Vogel-type conflict test (VTCT), elevated plus-maze test (EPMT), and open-field test (OFT) were conducted. Data showed that similar to the positive-control drug sertraline (Ser) (15 mg/kg, i.g.), the anxiolytic-like effects were produced by puerarin (60 and 120 mg/kg, i.g.) in VTCT and EMPT respectively without affecting locomotor activity in OFT. Moreover, the present study also found that consistent with Ser, the levels of allopregnanolone and serotonin (5-HT) in the prefrontal cortex and hippocampus were increased by puerarin (60 and 120 mg/kg, i.g.), respectively. In summary, the present study indicated that puerarin exerted the anxiolytic-like effects, which maybe associated with normalization of 5-HT levels and biosynthesis of allopregnanolone in brain.

A new member of the contryphans family was isolated from the venom of Conus betilinus, a vermivorous species distributed in the South China Sea. Its sequence, ZSGCO(D-W)KPWC-NH 2 (Z, pyroglutamic acid), was established by a combination of de novo MS/MS sequencing and venom-duct transcriptome sequencing. The occurrence of D-Trp 6 was confirmed by chemical synthesis and HPLC behavior comparison. Like known contryphans, contryphan-Bt produces the “stiff-tail” syndrome in mice and contains one disulfide bond, a hydroxyproline, a D-tryptophan, and an amidated C-terminus. However, contryphan-Bt differs from previously identified contryphans by a pyroglutamic acid at the N terminus. CD spectrum reveals that contryphan-Bt possess β-turn in solution.

Nanotips made of metal and semiconductor have been widely utilized in versatile applications to strengthen the electric field through lightning rod effect and localized surface plasmon resonance (LSPR) effect. Here, we present the utilization of ferroelectric nanotips to assist photoreduction of silver nanostructures for surface enhanced Raman scattering (SERS). Ferroelectric nanotips with spontaneous polarization posses the unique feature of producing the permanent electrostatic field without requiring external excitation, which differs from the present nanotips requiring electrical and optical excitation. The enhanced electrostatic field promotes the formation of silver nanoparticles by reducing the effect of Stern layer and accelerating the movement of photoelectrons and silver ions to the template surface. Experimental results show that sharp ferroelectric nanotips facilitate the formation of large-diameter nanoparticles with strong LSPR action. Compared to the conventional ferroelectric templates, the SERS substrates using nanotip-equipped ferroelectric templates produce 5.51 times larger Raman intensity, which can be further increased by >10.76 times by increasing the reaction time. The proposed SERS substrate owns the limit of detection −8 M and the enhancement factor of 2.3 × 109. The presented ferroelectric nanotips with permanent electrostatic field would open promising applications in the versatile areas, such as nanomaterial fabrication and optoelectronic devices.

The venom of each Conus species consists of a diverse array of neurophysiologically active peptides, which are mostly unique to the examined species. In this study, we performed high-throughput transcriptome sequencing to extract and analyze putative conotoxin transcripts from the venom ducts of 3 vermivorous cone snails (C. caracteristicus, C. generalis, and C. quercinus), which are resident in offshore waters of the South China Sea. In total, 118, 61, and 48 putative conotoxins (across 22 superfamilies) were identified from the 3 Conus species, respectively, most of them are novel, and some possess new cysteine patterns. Interestingly, a series of 45 unassigned conotoxins presented with a new framework of C-C-C-C-C-C, and their mature regions were sufficiently distinct from any other known conotoxins, most likely representing a new superfamily. O- and M-superfamily conotoxins were the most abundant in transcript number and transcription level, suggesting their critical roles in the venom functions of these vermivorous cone snails. In addition, we identified numerous functional proteins with potential involvement in the biosynthesis, modification, and delivery process of conotoxins, which may shed light on the fundamental mechanisms for the generation of these important conotoxins within the venom duct of cone snails.

Photoreduction using ferroelectric templates is an emerging green technique for the production of noble-metal nanostructures by a reductant-free process. In this work, anisotropic growth of silver nanostructures is stimulated by a surfactant-assisted photoreduction process on ferroelectric templates. The preferential adsorption of surfactant (polyvinylpyrrolidone) on the specific facets of silver creates the anisotropic growth of nanostructures and thus the formation of silver nanoplates. The surfactant adsorption effects on the nanoparticle morphology and the nanoparticle properties are studied. Their influence levels depend on the ratio of surfactant concentration to precursor concentration. The produced silver nanostructures have superior SERS features, such as the limit of detection of

Post-traumatic stress disorder (PTSD) is a severe psychiatric condition. The allopregnanolone biosynthesis has been implicated as one of the possible contributors to PTSD. Inulin-type oligosaccharides of morinda officinalis (IOMO) had been shown to be effective in the therapy of depression. However, few studies concern the anti-PTSD-like effects of IOMO. To evaluate this, the single prolonged stress (SPS) model was used in the present study. It had been shown that the behavioral deficits of SPS-treated rats were reversed by IOMO (25.0 and 50.0 mg/kg, i.p.), which reversed the increased freezing time in contextual fear paradigm (CFP) and the decreased time and entries in open arms in the elevated plus maze (EPM) test without affecting the locomotor activity in the open field (OF) test. In addition, the decreased allopregnanolone in the prefrontal cortex, hippocampus, and amygdala was reversed by IOMO (25.0 and 50.0 mg/kg, i.p.), respectively. In summary, the present study indicated that the IOMO exert anti-PTSD-like behaviors, which maybe associated with the brain allopregnanolone biosynthesis.

The study was aimed to investigate the absorption and metabolism of oxymatrine (OMT) which contributed to its poor bioavailability. Determinations of OMT absorption and metabolism in rats were evaluated using techniques of the in situ perfused rat intestine-liver preparation and recirculated intestine preparation. Furthermore, chemical inhibition experiments in rat liver microsomes were used to determine the principal cytochrome P450 (CYP) isoforms involved in OMT metabolism. In the intestine-liver preparation, the steady state liver extraction ratio (0.753 ± 0.054) of OMT was 33 times higher than that for the intestine (0.023 ± 0.002). The portal vein mainly consisted of OMT, and was devoid of the metabolite matrine, whereas both OMT and matrine were detected in hepatic vein. With the intestine preparation, the extent of OMT absorption at the end of 120 min of perfusion was 4.79 ± 0.352%. The first-order rate constant for OMT absorption was 0.05 ± 0.003 min(-1). The inhibitor of CYP3A2 had strong inhibitory effect on OMT metabolism in a concentration-dependent manner, and value was reduced to 29.73% of control. The 2 perfusion techniques indicated that poor bioavailability of OMT in rats is due mostly to poor absorption and higher hepatic elimination and CYP3A2 appears to contribute to OMT metabolism in rat liver.

Defective autophagy in vascular smooth muscle cells (VSMCs) is the principal cause of atherosclerosis. This study aimed to investigate the effect of astragaloside IV (AS-IV) on VSMCs autophagy. In vivo, ApoE−/− mice were fed with high-fat diet ad libitum for eight weeks, with or without AS-IV (25 mg/kg, daily). In vitro, human VSMCs were cultured and treated with β-Glycerophosphate (10 mmol/L) and AS-IV (50 μg/ml). VSMCs autophagy, mineralization, expression of p-ERK1/2, p-mTOR, and autophagy-related proteins (LC3 II/I, p62, and Beclin 1) were detected. Increased autophagy and mineralization was observed in VSMCs in thoracic aorta of mice and in in vitro VSMCs model of atherosclerosis. AS-IV administration attenuated the autophagy and mineralization in VSMCs. Reverse expression profiles of H19 and DUSP5 were observed. AS-IV inhibited DUSP5 and autophagy-related proteins and increased expression of H19, level of p-ERK1/2 and p-mTOR. Further, autophagy and mineralization level in VSMCs were in line with DUSP5 expression level, but in contrast to H19, p-ERK1/2, and p-mTOR profiles. We demonstrated that AS-IV could attenuate autophagy and mineralization of VSMCs in atherosclerosis, which may be associated with H19 overexpression and DUSP5 inhibition.

Post-traumatic stress disorder (PTSD) is a severe psychiatric condition defined as a "trauma and stress-related disorder". Dampened allopregnanolone biosynthesis has been implicated as a possible contributor to PTSD aetiology. Free and Easy Wanderer Plus (FEWP) is a traditional Chinese medicine previously shown to be effective in PTSD treatment. However, little is known about the role of allopregnanolone in the anti-PTSD effects of FEWP. To evaluate this, the single prolonged stress (SPS) model was used in the present study. SPS-induced rats were administered FEWP (at doses of 2.5, 5.0 and 10.0 mg/kg, p.o.) after induction of SPS from days 2 through 15. After exposure to SPS, behavioral assessments were determined, including the open-field test, the contextual fear paradigm, and the elevated plus-maze test. The experimental model rats were decapitated at the end of the behavioral tests and the level of allopregnanolone in the prefrontal cortex, hippocampus and amygdala was measured by enzyme linked immunosorbent assay (ELISA). The behavioral deficits of the SPS-induced rats were significantly reversed by FEWP (at doses of 5.0 and 10.0 mg/kg, p.o.). The level of allopregnanolone was increased by administration of FEWP. In summary, this study indicated that the anti-PTSD effects of FEWP were associated with allopregnanolone biosynthesis.

The present study aimed to investigate the mechanisms underlying the antidepressant-like effects of puerarin via the chronic unpredictable stress (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by reversing the decreased sucrose preference in sucrose preference test (SPT), by blocking the increased latency to feed in novelty-suppressed feeding test (NSFT) and the increased immobility time in forced swimming test (FST) without affecting locomotor activity. However, acute puerarin treatment did not ameliorate the antidepressant- and anxiolytic- like effects in FST and NSFT, respectively. In addition, enzyme linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemical detection (HPLC-ECD) showed that chronic treatment of puerarin (60 and 120 mg/kg, i.g) reversed the decreased levels of progesterone, allopregnanolone, serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus of post-CUS rats. Furthermore, puerarin (60 and 120 mg/kg, i.g) blocked the increased corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH). Collectively, repeated administration of puerarin alleviated the behavioral deficits induced by chronic stress which was associated with the biosynthesis of neurosteroids, normalization of serotonergic system and preventing HPA axis dysfunction.

Post-traumatic stress disorder (PTSD) has become a major psychiatric and neurological issue. Resveratrol is shown to be effective on depression and anxiety. However, the mechanism of anti-PTSD-like effects of resveratrol remains unknown. The present study aimed to explore the possible molecular and cellular mechanisms underlying the anti-PTSD-like effects of resveratrol. Following a 2-day exposure to inescapable electric foot shocks, animals were administered resveratrol (10, 20, and 40mg/kg, i.g.) during the behavioral tests, which included contextual freezing measurement, elevated plus maze test, staircase test, and open field test. Similar to the positive control drug sertraline (15mg/kg, i.g.), the behavioral deficits of stressed mice were blocked by resveratrol (20 and 40mg/kg, i.g.), which reversed the increased freezing time in contextual freezing measurement and the number of rears in the staircase test and blocked the decrease in time and number of entries in open arms in the elevated plus maze test without affecting the locomotor activity in the open field test. In addition, resveratrol (20 and 40mg/kg, i.g.) antagonized the decrease in the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. Furthermore, long-term resveratrol attenuated the dysfunctions of hypothalamic-pituitary-adrenal axis simultaneously. Collectively, the evidence indicated that the anti-PTSD-like effects of resveratrol were associated with the normalization of biosynthesis of neurosteroids in the brain and prevention of the hypothalamic-pituitary-adrenal axis dysfunction.

The thermal and electrical transport properties of an ideal anyon gas within fractional exclusion statistics are studied. By solving the Boltzmann equation with the relaxation-time approximation, the analytical expressions for the thermal and electrical conductivities of a three-dimensional ideal anyon gas are given. The low-temperature expressions for the two conductivities are obtained by using the Sommerfeld expansion. It is found that the Wiedemann—Franz law should be modified by the higher-order temperature terms, which depend on the statistical parameter g for a charged anyon gas. Neglecting the higher-order terms of temperature, the Wiedemann—Franz law is respected, which gives the Lorenz number. The Lorenz number is a function of the statistical parameter g.

Diabetes mellitus is a chronic disease that is associated with depression. Also, depression is common in adults with type 2 diabetes mellitus (T2DM). Translocator protein (18kDa) (TSPO) and allopregnanolone play an important role in the depression treatment. However, few studies have evaluated TSPO and allopregnanolone in the treatment of depression in T2DM. AC-5216, a ligand for TSPO, produces anxiolytic- and antidepressant-like effects in animal models. The present study aimed to explore antidepressant-like effects of AC-5216 on diabetic rats. Following the development of diabetic model induced by high fat diet (HFD) feeding and streptozotocin (STZ), AC-5216 (0.3 and 1 mg/kg, i.g.) elicited the antidepressant-like effects in behavioral tests while these activities were blocked by TSPO antagonist PK11195 (3 mg/kg, i.p.). The levels of allopregnanolone in the prefrontal cortex and hippocampus were increased by AC-5216 (0.3 and 1 mg/kg, i.g.), which was antagonized by PK11195 (3 mg/kg, i.p.). The increased plasma glucose (PG) and decreased insulin (INS) in HFD-STZ rats were reversed by AC-5216 (0.3 and 1 mg/kg, i.g.). This study indicates that the antidepressant-like effects of AC-5216 on HFD-STZ rats, suggesting that TSPO may represent a novel therapeutic target for depression in T2DM.

μ-Conotoxin GIIIA, a peptide toxin isolated from Conus geographus, preferentially blocks the skeletal muscle sodium channel NaV1.4. GIIIA folds compactly to a pyramidal structure stabilized by three disulfide bonds. To assess the contributions of individual disulfide bonds of GIIIA to the blockade of NaV1.4, seven disulfide-deficient analogues were prepared and characterized, each with one, two, or three pairs of disulfide-bonded Cys residues replaced with Ala. The inhibitory potency of the analogues against NaV1.4 was assayed by whole cell patch-clamp on rNaV1.4, heterologously expressed in HEK293 cells. The corresponding IC50 values were 0.069 ± 0.005 μM for GIIIA, 2.1 ± 0.3 μM for GIIIA-1, 3.3 ± 0.2 μM for GIIIA-2, and 15.8 ± 0.8 μM for GIIIA-3 (-1, -2 and -3 represent the removal of disulfide bridges Cys3–Cys15, Cys4–Cys20 and Cys10–Cys21, respectively). Other analogues were not active enough for IC50 measurement. Our results indicate that all three disulfide bonds of GIIIA are required to produce effective inhibition of NaV1.4, and the removal of any one significantly lowers its sodium channel binding affinity. Cys10–Cys21 is the most important for the NaV1.4 potency.

Marine polyether toxins, mainly produced by marine dinoflagellates, are novel, complex, and diverse natural products with extensive toxicological and pharmacological effects. Owing to their harmful effects during outbreaks of marine red tides, as well as their potential value for the development of new drugs, marine polyether toxins have been extensively studied, in terms of toxicology, pharmacology, detection, and analysis, structural identification, as well as their biosynthetic mechanisms. Although the biosynthetic mechanisms of marine polyether toxins are still unclear, certain progress has been made. In this review, research progress and current knowledge on the biosynthetic mechanisms of polyether toxins are summarized, including the mechanisms of carbon skeleton deletion, pendant alkylation, and polyether ring formation, along with providing a summary of mined biosynthesis-related genes. Finally, future research directions and applications of marine polyether toxins are discussed.

In this paper, we investigate excited characteristic of the weakly interacting quasi-one-dimensional (1D) and quasi-two-dimensional (2D) Bose—Einstein condensation (BEC) in harmonic potential trap. The energy spectrum and the analytical expression of the sound velocity are obtained and analyzed. Compared with 3-Dimensional homogeneous Bose-condensed gas occasion, the sound velocity of 2D Bose-Einstein condensation in harmonic potential trap is smaller.

Ethnopharmacology relevance Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder that is characterized by symptoms of re-experiencing, avoidance and hyperarousal, as well as social and professional dysfunction at least one month after the exposure to a traumatic event. Biosynthesis of allopregnanolone has been suggested as one of the important contributors to PTSD. Albiflorin (AF) extracted from Radix paeoniae Alba had been shown to be effective in the therapy of depression. However, few studies were concerned about the anti-PTSD-like effects of AF. Aim of the study The current study aimed to evaluate the anti-PTSD-like effects of AF in an animal model and its possible mechanism. Materials and methods To evaluate this, the single prolonged stress (SPS) model was used in the present study. The SPS rats were administered by AF (at doses of 3.5, 7 and 14.0 mg/kg, i.g.) after induction of SPS from days 2–13. After the exposure to SPS, behavioral assessments were conducted, including contextual fear paradigm (CFP), elevated plus-maze test (EPMT), open-field test (OFT). The rats were decapitated at the end of the behavioral tests and levels of allopregnanolone in prefrontal cortex, hippocampus and amygdala were measured by enzyme linked immunosorbent assay (ELISA). Results It had been shown that behavioral deficits of SPS rats were reversed by AF (7.0 and 14.0 mg/kg, i.g.), which attenuated the PTSD-like associated contextual freezing behavior in CFP and improved PTSD-like associated anxiogenic behavior in EPMT without affecting locomotor activity in OFT. Moreover, decreased levels of allopregnanolone in prefrontal cortex, hippocampus, and amygdala were reversed by AF (7.0 and 14.0 mg/kg, i.g.), respectively. Conclusion In summary, the present study indicated that AF exerted the anti-PTSD-like effects, which maybe associated with allopregnanolone biosynthesis in the brain.

Background The venom of predatory marine cone snails mainly contains a diverse array of unique bioactive peptides commonly referred to as conopeptides or conotoxins. These peptides have proven to be valuable pharmacological probes and potential drugs because of their high specificity and affinity to important ion channels, receptors and transporters of the nervous system. Most previous studies have focused specifically on the conopeptides from piscivorous and molluscivorous cone snails, but little attention has been devoted to the dominant vermivorous species. Results The vermivorous Chinese tubular cone snail, Conus betulinus, is the dominant Conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in the identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including nine new superfamilies. It appeared that most of the identified conopeptides were synthesized in the venom duct, while a handful of conopeptides were identified only in the venom bulb and at very low levels. Conclusions We identified 215 unique putative conopeptide transcripts from the combination of five transcriptomes and one EST sequencing dataset. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for the development of new pharmaceuticals, and a pathway for the discovery of new conotoxins. Electronic supplementary material The online version of this article (doi:10.1186/s13742-016-0122-9) contains supplementary material, which is available to authorized users.

The finite-temperature Pauli paramagnetic susceptibility of a three-dimensional ideal anyon gas obeying Haldane fractional exclusion statistics is studied analytically. Different from the result of an ideal Fermi gas, the susceptibility of an ideal anyon gas depends on a statistical factor g in Haldane statistics model. The low-temperature and high-temperature behaviors of the susceptibility are investigated in detail. The Pauli paramagnetic susceptibility of the two-dimensional ideal anyons is also derived. It is found that the reciprocal of the susceptibility has the similar factorizable property which is exhibited in some thermodynamic quantities in two dimensions.

The analytical expressions for the zero-temperature sound velocity and low-energy eigenfrequencies of a disk-shaped harmonically trapped three-dimensional superfluid Fermi gas are derived on the basis of the hydrodynamic theory in the regimes along the Bardeen-Cooper-Schrieffer (BCS) to Bose-Einstein condensation (BEC) crossover. Theoretically, by plotting the sound velocity as a function of 1/(k F a), it finds that there is an obvious flat behavior for the sound velocity in a disk-shaped trap around unitarity. However, there is no such flat behavior for a cigar-shaped Fermi gas at the same superfluid regime. Here, k F is the Fermi wave vector and a is the s-wave scattering length.

We investigate the properties of a trapped two-component, Fermi gas near the unitary limit regime. The bulk properties are discussed through a quasi-linear approximation with a medium dependent effective interaction. The obtained ground state energy for the unitary fermion system is in good agreement with existing theoretical predictions as well as experimental results. Within the framework of hydrodynamics, the radial and axial frequencies of the breathing modes are analyzed in detail. Applied to the cigar shaped harmonic trap, the theoretical results are reasonably consistent with the experimental measurements.

An effective Proca Lagrangian action is used to address the vector condensation Lorentz violation effects on the equation of state of the strongly interacting fermions system. The interior quantum fluctuation effects are incorporated as an external field approximation indirectly through a fictive generalized Thomson Problem counterterm background. The general analytical formulas for the $d$-dimensions thermodynamics are given near the unitary limit region. In the non-relativistic limit for $d=3$, the universal dimensionless coefficient $\xi ={4}/{9}$ and energy gap $\Delta/\epsilon_f ={5}/{18}$ are reasonably consistent with the existed theoretical and experimental results. In the unitary limit for $d=2$ and T=0, the universal coefficient can even approach the extreme occasion $\xi=0$ corresponding to the infinite effective fermion mass $m^*=\infty$ which can be mapped to the strongly coupled two-dimensions electrons and is quite similar to the three-dimensions Bose-Einstein Condensation of ideal boson gas. Instead, for $d=1$, the universal coefficient $\xi$ is negative, implying the non-existence of phase transition from superfluidity to normal state. The solutions manifest the quantum Ising universal class characteristic of the strongly coupled unitary fermions gas., Comment: Improved version

The translocator protein (18 kDa) (TSPO) plays an important role in stress-related disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD), caused by neurosteroids (e.g. allopregnanolone). The present study sought to evaluate the significance of TSPO in anxiolytic and antidepressant effects induced by midazolam. The animals were administrated midazolam (0.25, 0.5 and 1 mg/kg, i.p.) and subjected to behavioral tests, including Vogel-type conflict test, elevated plus-maze test, forced swimming test. Midazolam produced anxiolytic- and antidepressant-like effects Vogel-type conflict test (1 mg/kg, i.p.), elevated plus-maze test (0.5 and 1 mg/kg, i.p.), and forced swimming test (0.5 and 1 mg/kg, i.p.). These effects of Midazolam were totally blocked by the TSPO antagonist PK11195 (3 mg/kg, i.p.). To evaluate the role of allopregnanolone in the anxiolytic- and antidepressant-like effects of midazolam, the animals were decapitated at the end of the behavioral tests. The allopregnanolone levels of the prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The allopregnanolone level of the prefrontal cortex and hippocampus was increased by midazolam (0.5, 1 mg/kg, i.p.) and the increase was reversed by PK11195 (3 mg/kg, i.p.). Overall, the results indicated that the anxiolytic- and antidepressant-like effects of midazolam were mediated by TSPO, via stimulation of allopregnanolone biosynthesis.

Cone snails are tropical marine mollusks that envenomate prey with a complex mixture of neuropharmacologically active compounds for the purpose of feeding and defence, each evolved to act in a highly specific manner on different parts of the nervous system. Here, we report the peptide purification, molecular cloning, chemical synthesis, and functional characterization of a structurally unique toxin isolated from the venom of Conus vexillum. The novel peptide, designated Vx2, was composed of 21 amino acid residues cross-linked by 3 disulfide bonds (WIDPSHYCCCGGGCTDDCVNC). Intriguingly, its mature peptide sequence shows low level of similarity with other identified conotoxins, and its unique motif (-CCCGGGC-) was not reported in other Conus peptides. However, its signal peptide sequence shares high similarity with those of the M-superfamily conotoxins. Hence, Vx2 could be classified into a new family of the M-superfamily.

The $^1 S_0$ pairing of symmetric nuclear matter is discussed in the frame work of relativistic nuclear theory with Dyson-Schwinger equations (DSEs). The in-medium nucleon and meson propagators are treated in a more self-consistent way through meson polarizations. The screening effects on mesons due to in-medium nucleon excitation are found to reduce the $^1S_0$ pairing gap and shift remarkably the gap peak to low density region., 5 pages, identical to published version in PLB with typos corrected

A novel conotoxin, kappa-conotoxin (kappa-BtX), has been purified and characterized from the venom of a worm-hunting cone snail, Conus betulinus. The toxin, with four disulfide bonds, shares no sequence homology with any other conotoxins. Based on a partial amino acid sequence, its cDNA was cloned and sequenced. The deduced sequence consists of a 26-residue putative signal peptide, a 31-residue mature toxin, and a 13-residue extra peptide at the C terminus. The extra peptide is cleaved off by proteinase post-processing. All three Glu residues are gamma-carboxylated, one of the two Pro residues is hydroxylated at position 27, and its C-terminal residue is Pro-amidated. The monoisotopic mass of the toxin is 3569.0 Da. Electrophysiological experiments show that: 1) among voltage-gated channels, kappa-BtX is a specific modulator of K(+) channels; 2) among the K channels, kappa-BtX specifically up-modulates the Ca(2+)- and voltage-sensitive BK channels (252 +/- 47%); 3) its EC(50) is 0.7 nm with a single binding site (Hill = 0.88); 4) the time constant of wash-out is 8.3 s; and 5) kappa-BtX has no effect on single channel conductance, but increases the open probability of BK channels. It is concluded that kappa-BtX is a novel specific biotoxin against BK channels.

From the semiclassical kinetic equations and the mean field equation of quark–gluon plasma, the contribution of the color field self-coupling to the non-Abelian permittivity at the leading order in the weak coupling constant is analyzed. The nonlinear frequency drift has been estimated for the k=0 modes.

The damping rate of the collective modes of the unitary Fermi gas is an important experimental observable. It varies with experimental conditions, and provides information about the viscosity. In this paper, we simulate the axial breathing modes basing on viscous hydrodynamics, and extract the concrete relation between the temporal damping rate and the experimental parameters: viscosity, atom number and the trap frequencies.

AIM: To compare the staging systems for stratifying and predicting the prognosis of patients with hepatocellular carcinoma (HCC) after partial hepatectomy (PH). METHODS: Clinical data about 438 HCC patients who underwent PH from January 1991 to December 2004 at our hospital were retrospectively analyzed. Tumor stage was evaluated following the Chinese tumor node metastasis (TNM) and barcelona clinic liver cancer (BCLC) staging systems, respectively. Survival curves for the HCC patients were plotted using the Kaplan-Meier method and differences were compared by the log-rank test. The accuracy of each system for predicting death of HCC patients was evaluated by calculating the area under the receiver operating characteristic curve. RESULTS: The HCC patients were classified into stages I-III, stages I-IV and stages A-C, according to the 3 staging systems, respectively. Log-rank test showed that the cumulative survival rate was significantly different for the HCC patients at 3 Chinese system stages, TNM stages I and II, TNM stages III and IV, and 3 BCLC stages (P < 0.05). However, no significant difference was found in the HCC patients at TNM stages II and III. The accuracy of the Chinese and BCLC staging systems was higher than that of the TNM staging system for predicting the survival rate of HCC patients. CONCLUSION: The Chinese and BCLC staging systems are better for stratifying and predicting the prognosis of HCC patients after PH than the TNM staging system.

We utilize a fractional exclusion statistics of Haldane and Wu hypothesis to study the thermodynamics of a unitary Fermi gas trapped in a harmonic oscillator potential at ultra-low finite temperature. The entropy per particle as a function of the energy per particle and energy per particle versus rescaled temperature are numerically compared with the experimental data. The study shows that, except the chemical potential behavior, there exists a reasonable consistency between the experimental measurement and theoretical attempt for the entropy and energy per particle. In the fractional exclusion statistics formalism, the behavior of the isochore heat capacity for a trapped unitary Fermi gas is also analyzed., Comment: 6 pages, 6 figures

Changes in endocochlear potentials (EP), cochlear microphonics (CM), and compound action potentials (CAP) with noise exposure were investigated in guinea pigs. The animals were anesthetized and immobilized and exposed to white noise at intensities ranging from 105 to 125 dB. The negative EP (N-EP) was induced by anoxia and was investigated during and after noise exposure. It was found that the general EP (G-EP, the sum of both positive EP (P-EP) and N-EP) increased remarkably during exposure to 115 dB noise but decreased during exposure to 125 dB noise. A smaller absolute value of N-EP was encountered only during exposure to 125 dB noise. The results shed light on the relationship between EP and CM, CAP changes, and the potential mechanism of EP change and its significance in noise-induced hearing loss.

To study the therapeutic effect of splenic autotransplantation combined with lower esophagus transaction anastomosis in the treatment of liver cirrhosis induced portal hypertension.Thirty-six patients admitted from January 2003 to December 2006 were randomly divided into splenic autotransplantation group undergoing splenic autotransplantation after splenectomy combined with lower esophagus transaction anastomosis, and splenectomy group only undergoing splenectomy combined with lower esophagus transaction anastomosis. The general conduction, splenic scanning, liver function, and the level of serum Tuftsin and IgM of each patient were observed before and after operation.The levels of Tuftsin and IgM in splenic autotransplantation group were significant higher than that of splenectomy group 2 months after the operation, and the liver function showed no significant difference between these two groups. Splenic tissue was detected in the retroperitoneal space by 99mTc-DRBC 2 months after operation.Splenic autotransplantation combined with lower esophagus transaction anastomosis is a safe and effective treatment strategy for patients with liver cirrhosis induced portal hypertension, and the spleen tissue transplanted into the retroperitoneal space can partially preserve the immune function.