Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.

Humans have long been combating chronic pain. In clinical practice, opioids are first- choice analgesics, but long-term use of these drugs can lead to serious adverse reactions. Finding new, safe and effective pain relievers that are useful treatments for chronic pain is an urgent medical need. Based on accumulating evidence from numerous studies, excess reactive oxygen species (ROS) contribute to the development and maintenance of chronic pain. Some antioxidants are potentially beneficial analgesics in the clinic, but ROS-dependent pathways are completely inhibited only by scavenging ROS directly targeting cellular or subcellular sites. Unfortunately, current antioxidant treatments donot achieve this effect. Furthermore, some antioxidants interfere with physiological redox signaling pathways and fail to reverse oxidative damage. Therefore, the key upstream processes and mechanisms of ROS production that lead to chronic pain in vivo must be identified to discover potential therapeutic targets related to the pathways that control ROS production in vivo. In this review, we summarize the sites and pathways involved in analgesia based on the three main mechanisms by which ROS are generated in vivo, discuss the preclinical evidence for the therapeutic potential of targeting these pathways in chronic pain, note the shortcomings of current research and highlight possible future research directions to provide new targets and evidence for the development of clinical analgesics.

Evaluating Surgical Risk Using FMEA and MULTIMOORA Methods under a Single-Valued Trapezoidal Neutrosophic Environment.

BACKGROUND: Human errors during operations may seriously threaten patient recovery and safety and affect the doctor-patient relationship. Therefore, risk evaluation of the surgical process is critical. Risk evaluation by failure mode and effect analysis (FMEA) is a prospective technology that can identify and evaluate potential failure modes in the surgical process to ensure surgical quality and patient safety. In this study, a hybrid surgical risk-evaluation model was proposed using FMEA and multiobjective optimization on the basis of ratio analysis plus full multiplicative form (MULTIMOORA) method under a single-valued trapezoidal neutrosophic environment. This work aimed to determine the most critical risk points during the surgical process and analyze corresponding solutions. METHODS: A team for FMEA was established from domain experts from different departments in a hospital in Hunan Province. Single-valued trapezoidal neutrosophic numbers (SVTNNs) were used to evaluate potential risk factors in the surgical process. Cmprehensive weights combining subjective and objective weights were determined by the best-worst method and entropy method to differentiate the importance of risk factors. The SVTNN-MULTIMOORA method was utilized to calculate the risk-priority order of failure modes in a surgical process. RESULTS: The hybrid FMEA model under the SVTNN-MULTIMOORA method was used to calculate the ranking of severity of 21 failure modes in the surgical process. An unclear diagnosis is the most critical failure in the surgical process of a hospital in Hunan Province. CONCLUSION: The proposed model can identify and evaluate the most critical potential failure modes of the surgical process effectively. In addition, such a model can help hospitals to reduce surgical risk and improve the safety of surgery.

Selective hydrogenation of nitroaromatics to N-arylhydroxylamines in a micropacked bed reactor with passivated catalyst.

In this contribution, a protocol was established for the selective catalytic hydrogenation of nitroarenes to the corresponding N-arylhydroxylamines. The reduction of 1-(4-chlorophenyl)-3-((2-nitrobenzyl)oxy)-1H-pyrazole, an intermediate in the synthesis of the antifungal reagent pyraclostrobin that includes carbon-chlorine bonds, benzyl groups, carbon-carbon double bonds and other structures that are easily reduced, was chosen as the model reaction for catalyst evaluation and condition optimization. Extensive passivant evaluation showed that RANEY®-nickel treated with ammonia/DMSO (1 : 10, v/v) afforded the optimal result, especially with a particle size of 400-500 mesh. To combine the modified catalyst with continuous-flow reaction technology, the reaction was conducted at room temperature, rendering the desired product with a conversion rate of 99.4% and a selectivity of 99.8%. The regeneration of catalytic activity was also studied, and an in-column strategy was developed by pumping the passivate liquid overnight. Finally, the generality of the method was explored, and 7 substrates were developed, most of which showed a good conversion rate and selectivity, indicating that the method has a certain degree of generality.

[Effects of Different Concentrations of Ammonia Nitrogen on the Growth and Enzyme Activity of Four Common Algae Strains].

Treating swine wastewater with a high ammonia nitrogen content with microalgae cultures has proved difficult. In this paper, the strains Chlamydomonas 715, Botryococcus braunii 357, Porphyridium cruentum 806, and Scenedesmus obliquus 417 were tested. Ammonia nitrogen concentrations of 50 mg·L-1, 500 mg·L-1, and 2000 mg·L-1 applied to the media according to the concentrations of biogas slurry. This allowed the effect of different concentrations of ammonia nitrogen on the growth and cell enzyme activity of microalgae to be tested. The results showed that the growth of Chlamydomonas 715 and Scenedesmus obliquus 417 was inhibited at different concentrations of ammonia nitrogen, and the biomass and biomass productivities were lower than for the normal media. However, the biomass and biomass productivity of Porphyridium cruentum 806 in 50 mg·L-1 ammonia nitrogen were 1.78 g·L-1 and 0.16 g·(L·d)-1, respectively, which were higher than the values obtained using KOCK medium. Furthermore, the biomass and biomass productivity of Botryococcus braunii 357 in 500 mg·L-1 ammonia nitrogen were 1.95 g·L-1 and 0.18 g·(L·d)-1, respectively, which were higher than the values obtained using BG11 medium. The SOD, POD, and CAT of all algae species showed a decreasing tendency in response to an increase in the concentration of ammonia nitrogen, as did MDA. These results provide a theoretical basis for the treatment of swine wastewater with high ammonia nitrogen content using microalgae cultures.

Exogenic glucose as an electron donor for algal hydrogenases to promote hydrogen photoproduction by Chlorella pyrenoidosa.

In this work, glucose addition (0.7 g l-1) almost doubled hydrogen yield of Chlorella pyrenoidosa (121.1 ml l-1 vs 65.5 ml l-1), with a positive correlation between hydrogen production and glucose consumption (-0.977, P < 0.01). When the electrons transport from water photolysis to algal hydrogenase was inhibited, the hydrogen productivity declined by 21.1%; whereas it dramatically decreased by 70.9% when the algal nicotinamide adeninedinucleotide dehydrogenase (NADH) was inhibited. Therefore, in the presence of glucose, the electrons for algae based hydrogen production would be mainly from glucose glycolysis rather than water photolysis. Further deuterated-glucose trial indicated that the glucose might serve as an electron donor for algal hydrogenases. Finally, a tentative electron transport route from glucose to algal hydrogenase was proposed, hoping to provide more scientific direction for further algae-based hydrogen production improvement.

A novel financial risk assessment model for companies based on heterogeneous information and aggregated historical data.

The financial risk not only affects the development of the company itself, but also affects the economic development of the whole society; therefore, the financial risk assessment of company is an important part. At present, numerous methods of financial risk assessment have been researched by scholars. However, most of the extant methods neither integrated fuzzy sets with quantitative analysis, nor took into account the historical data of the past few years. To settle these defects, this paper proposes a novel financial risk assessment model for companies based on heterogeneous multiple-criteria decision-making (MCDM) and historical data. Subjective and objective indexes are comprehensively taken into consideration in the financial risk assessment index system of the model, which combines fuzzy theory with quantitative data analysis. Moreover, the assessment information obtained from historical financial information of company, credit rating agency and decision makers, including crisp numbers, triangular fuzzy numbers and neutrosophic numbers. Furthermore, the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method is used to determine the ranking order of companies according to their financial risk. Finally, an empirical study of financial risk assessment for companies is conducted, and the results of comparative analysis and sensitivity analysis suggest that the proposed model can effectively and reliably obtain the company with the lowest financial risk.

Enhancing Astaxanthin Accumulation in Haematococcus pluvialis by Coupled Light Intensity and Nitrogen Starvation in Column Photobioreactors.

Natural astaxanthin mainly derives from a microalgae producer, Haematococcus pluvialis. The induction of nitrogen starvation and high light intensity is particularly significant for boosting astaxanthin production. However, the different responses to light intensity and nitrogen starvation needed to be analyzed for biomass growth and astaxanthin accumulation. The results showed that the highest level of astaxanthin production was achieved in nitrogen starvation, and was 1.64 times higher than the control group at 11 days. With regard to the optimization of light intensity utilization, it was at 200 µmo/m²/s under nitrogen starvation that the highest astaxanthin productivity per light intensity was achieved. In addition, both high light intensity and a nitrogen source had significant effects on multiple indicators. For example, high light intensity had a greater significant effect than a nitrogen source on biomass dry weight, astaxanthin yield and astaxanthin productivity; in contrast, nitrogen starvation was more beneficial for enhancing astaxanthin content per dry weight biomass. The data indicate that high light intensity synergizes with nitrogen starvation to stimulate the biosynthesis of astaxanthin.

Unexpected invasion of miniature inverted-repeat transposable elements in viral genomes.

BACKGROUND: Transposable elements (TEs) are common and often present with high copy numbers in cellular genomes. Unlike in cellular organisms, TEs were previously thought to be either rare or absent in viruses. Almost all reported TEs display only one or two copies per viral genome. In addition, the discovery of pandoraviruses with genomes up to 2.5-Mb emphasizes the need for biologists to rethink the fundamental nature of the relationship between viruses and cellular life. RESULTS: Herein, we performed the first comprehensive analysis of miniature inverted-repeat transposable elements (MITEs) in the 5170 viral genomes for which sequences are currently available. Four hundred and fifty one copies of ten miniature inverted-repeat transposable elements (MITEs) were found and each MITE had reached relatively large copy numbers (some up to 90) in viruses. Eight MITEs belonging to two DNA superfamilies (hobo/Activator/Tam3 and Chapaev-Mirage-CACTA) were for the first time identified in viruses, further expanding the organismal range of these two superfamilies. TEs may play important roles in shaping the evolution of pandoravirus genomes, which were here found to be very rich in MITEs. We also show that putative autonomous partners of seven MITEs are present in the genomes of viral hosts, suggesting that viruses may borrow the transpositional machinery of their cellular hosts' autonomous elements to spread MITEs and colonize their own genomes. The presence of seven similar MITEs in viral hosts, suggesting horizontal transfers (HTs) as the major mechanism for MITEs propagation. CONCLUSIONS: Our discovery highlights that TEs contribute to shape genome evolution of pandoraviruses. We concluded that as for cellular organisms, TEs are part of the pandoraviruses' diverse mobilome.

[Purification Effect of Piggery Wastewater with Chlorella pyrenoidosa by Immobilized Biofilm-Attached Culture].

Piggery wastewater treatment with microalgae is a biological recycling technology. To evaluate the purification effect, this study investigated the treatment of piggery wastewater at different dilution ratios with Chlorella pyrenoidosa by attached cultivation and lipid production of algae cells and explored the tolerance of Chlorella pyrenoidosa to the piggery wastewater, which has high ammonia nitrogen. The piggery wastewater was diluted with purified water 1-, 2-, 5-, and 10-fold in culture media. The removal efficiencies of COD, ammonia nitrogen, total nitrogen, and total phosphorus and the enrichment effect of the heavy metals copper, zinc, and iron were measured. Meanwhile, we investigated the lipid production of Chlorella pyrenoidosa in variously diluted wastewater (1-, 2-, 5-, and 10-fold). It turned out that the purification effects of COD, ammonia nitrogen, total nitrogen, and total phosphorus were best when the piggery wastewater was diluted 5-fold, and the removal efficiencies were 86.8%, 94.1%, 85.2%, and 84.3%, respectively. Correspondingly, the lipid content was as high as 32.7%, and the removal efficiencies of the heavy metals copper, zinc, and iron were 72.9%, 70.0%, and 73.0%, respectively. The biomass productivity was 4.21 g·(m2·d)-1 at the end of the experiment. This research makes an effective connection between microalgae and piggery wastewater, which is difficult to purify deeply, and provides a theoretical basis for achieving algal biofuel production and decreasing the cost of wastewater treatment.

[Coupling of Hydrocarbon Accumulation and Cobalt Removal During Treatment of Cobalt Enriched Industrial Wastewater with Botryococcus braunii Biofilm Attached Cultivation].

Industrial wastewater pollution is an increasing problem. The wastewater infiltrated cobalt is a key to purify wastewater because it is seriously hazardous and hard to treat. Traditional management method of heavy metals in industrial wastewater is difficult to apply. To seek for "green ecological" feasible approaches of industrial wastewater treatment, this paper studied the effect of industrial wastewater containing cobalt on the growth and hydrocarbon accumulation of Botryococcus braunii SAG 807-1 with biofilm attached cultivation. The research results obtained were as follows:B.braunii with biofilm attached cultivation could treat industrial wastewater, and 4.5 mg·L-1 cobalt could accelerate the accumulation of hydrocarbon while having little influence on the growth of B.braunii, the ability of B.braunii with biofilm attached cultivation to remove Co2+ from industrial wastewater was 1473.9 µmol·g-1, which was much higher than the report of P. littoralis culture. Through the study in this paper, the theoretical basis for the coupling of production of green high energy fuel hydrocarbon and industrial wastewater treatment was established.

[Research on Spectroscopy Spectrum De-Noising of Mineral Oil Based on Lifting Scheme Wavelet Transform].

The use of the mineral oil is an important cause of air pollution such as fog. The effectiveness and rapidity of the de-noising processing in mineral oil fluorescence spectroscopy detection system is a hot issue of the online real-time monitoring system. The de-noising method of the lifting wavelet transform (LWT) in the application of mineral oil fluorescence spectrum is proposed. Compared with traditional discrete wavelet transform (DWT), this wavelet transform method decomposes the existing wavelet filter module into the basic construction modules and steps to complete the transform with simplicity and a fast speed. There are characteristics of low computational complexity, in situ operation and the easy implement in the denoising process of mineral oil fluorescence spectra. The LWT can effectively solve the problems in these respects. The three methods of LWT, DWT and EMD are applied to the fluorescence spectra of 0# diesel oil, 97# gasoline and kerosene. The indicators evaluating de-noising effect such as the Signal-to-Noise Ratio (SNR), Mean Squared Error (MSE) and Normalied Correlation Coefficient (NCC) of the three kinds of mineral oil in the fluorescence spectra denoising prove the effectiveness of the lifting scheme wavelet transform in the application of mineral oil fluorescence spectrum. Meanwhile, the lifting scheme transform can improve the flexibility of structure and operation simplicity that makes the de-noising time reduced by 62%, validating the speediness of the de-noising method of the LWT in the application of mineral oil fluorescence spectrum and it is suitable for mineral oil fast de-noising processing system in real time.

[The Fluorescence Detection of Oil Pollutants Based on Self-Weighted Alternating Trilinear Decomposition].

The oil pollutants detector is designed in this paper. The pulse xenon lamp is used as light source; the step type multi-mode pure silica fiber is chosen to transmit the excitation and emission light. The asymmetric Czemy-Turner light path of high precision grating monochromator is adopted. The detector is applied to determine the fluorescence spectrum of diesel, gasoline and kerosene. The optimal excitation /emission wavelengths are: 290/330 nm (diesel)，270/300 nm (gasoline) and 280/330 nm (kerosene). The detection limits are: diesel (0.025 mg·L-1), gasoline (0.042 mg·L-1) and kerosene(0.054 mg·L-1). The relative errors are: diesel(2.55%), gasoline(2.06%) and kerosene(1.71%). Experiment results show that the designed detector has high accuracy of measurement. The different concentration of diesel, gasoline and kerosene mixed solution is configured, and three dimensional fluorescence spectra being measured. The self-weighted alternating trilinear decomposition is adopted to decompose the spectrum data. The predicted concentration and recovery rate show that self-weighted alternating trilinear decomposition has high resolution for mixed oil substance.

[A De-Noising Algorithm for Fluorescence Detection Signal of Mineral Oil in Water by SWT].

Fluorescence analysis is an important means of detecting mineral oil in water pollutants because of high sensitivity, selectivity, ease of design, etc. Noise generated from Photo detector will affect the sensitivity of fluorescence detection system, so the elimination of fluorescence signal noise has been a hot issue. For the fluorescence signal, due to the length increase of the branch set, it produces some boundary issues. The dbN wavelet family can flexibly balance the border issues, retain the useful signals and get. rid of noise, the de-noising effects of dbN families are compared, the db7 wavelet is chosen as the optimal wavelet. The noisy fluorescence signal is statically decomposed into 5 levels via db7 wavelet, and the thresholds are chosen adaptively based on the wavelet entropy theory. The pure fluorescence signal is obtained after the approximation coefficients and detail coefficients quantified by thresholds reconstructed. Compared with the DWT, the signal de-noised via SWT has the advantage of information integrity and time translation invariance.

Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum.

Major depressive disorder (MDD) is a highly prevalent, debilitating mental illness of importance for global health. However, its molecular pathophysiology remains poorly understood. Combined proteomics and metabolomics approaches should provide a comprehensive understanding of MDD's etiology. The present study reports novel "-omics" insights from a rodent model of MDD. Cerebellar samples from chronic mild stressed (CMS)-treated depressed rats and controls were compared with a focus on the differentially expressed proteins and metabolites using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and gas chromotography/mass spectrometry (GC-MS) metabolomics techniques, respectively. The combined analyses found significant alterations associated with cerebellar energy metabolism, as indicated by (1) abnormal amino acid metabolism accompanied by corresponding metabolic enzymatic alterations and disturbed protein turnover, (2) increased glycolytic and tricarboxylic acid (TCA) cycle enzyme levels paralleled by changes in the concentrations of associated metabolites, and (3) perturbation of ATP biosynthesis through adenosine accompanied by perturbation of the mitochondrial respiratory chain. To the best of our knowledge, this study is the first to integrate proteomics and metabolomics analyses to examine the pathophysiological mechanism(s) underlying MDD in a CMS rodent model of depression. These results can offer important insights into the pathogenesis of MDD.

Severe disturbance of glucose metabolism in peripheral blood mononuclear cells of schizophrenia patients: a targeted metabolomic study.

BACKGROUND: Schizophrenia is a widespread and debilitating mental disorder. However, the underlying molecular mechanism of schizophrenia remains largely unknown and no objective laboratory tests are available to diagnose this disorder. The aim of the present study was to characterize the alternations of glucose metabolites and identify potential diagnostic biomarkers for schizophrenia. METHODS: Gas chromatography/mass spectrometry based targeted metabolomic method was used to quantify the levels of 13 glucose metabolites in peripheral blood mononuclear cells (PBMCs) derived from healthy controls, schizophrenia and major depression subjects (n = 55 for each group). RESULTS: The majority (84.6%) of glucose metabolites were significantly disturbed in schizophrenia subjects, while only two (15.4%) glucose metabolites were differently expressed in depression subjects relative to healthy controls in both training set (n = 35/group) and test set (n = 20/group). Antipsychotics had only a subtle effect on glucose metabolism pathway. Moreover, ribose 5-phosphate in PBMCs showed a high diagnostic performance for first-episode drug-naïve schizophrenia subjects. CONCLUSION: These findings suggested disturbance of glucose metabolism may be implicated in onset of schizophrenia and could aid in development of diagnostic tool for this disorder.

Do soy isoflavones improve cognitive function in postmenopausal women? A meta-analysis.

OBJECTIVE: Several studies have demonstrated that soy isoflavone (SIF) supplementation can improve aspects of cognitive function. However, these findings remain controversial. We aimed to quantify the effects of SIF supplementation on improving cognitive function in postmenopausal women. METHODS: Databases and relevant Websites were searched for relevant studies up to March 2014. Two reviewers independently verified all potentially suitable randomized controlled trials (RCTs) using inclusion and exclusion criteria, and the quality of identified RCTs was assessed using the Jadad scale and the Risk of Bias Tool from the "Cochrane handbook for systematic reviews of interventions." Any disagreement on study quality or data extraction was resolved by consensus; a third reviewer was consulted if needed. Standardized mean differences (SMDs) in cognitive function test scores were calculated between SIF-treated and placebo-treated groups. RESULTS: We conducted a meta-analysis of 10 placebo-controlled RCTs of SIF supplementation (1,024 participants; treatment duration of 6 wk to 30 mo). The overall SMD in summary cognitive function test scores (0.08) was statistically significant (95% CI, 0.02-0.15; P = 0.014). The summary SMD for visual memory (0.10) was statistically significant (95% CI, 0.02-0.18; P = 0.016). In subgroup analyses, the statistically significant SMDs were as follows: 0.12 (95% CI, 0-0.25; P = 0.044) for non-US countries; 0.16 (95% CI, 0.05-0.28; P = 0.004) for mean age younger than 60 years; and 0.15 (95% CI, 0.03-0.27; P = 0.011) for treatment duration less than 12 months. CONCLUSIONS: SIF supplementation seems to have a positive effect on improving summary cognitive function and visual memory in postmenopausal women. There may be a critical window of opportunity in initiating SIF use at an earlier age in postmenopausal women, and geography and treatment duration seem to be factors influencing the effects of SIF supplementation. All individuals in the included studies should be followed up to observe the incidence rates of Alzheimer's disease and dementia, and future studies should report any adverse effects of SIF supplementation.

[Correlation of carbon monoxide with cell apoptosis in the penile tissue of aging rats].

OBJECTIVE: To explore the pathogenesis of male sexual dysfunction by studying cell apoptosis and carbonate monoxide (CO) contents in the penile tissue of rats at different ages. METHODS: We equally divided 24 male Wistar rats into an adult group (8 months old), an elderly group (16 months old) and an aged group (24 months old), and detected cell apoptosis by HE staining and TUNEL and CO levels in the penile tissues of different groups by modified dual-wavelength spectrophotometry. RESULTS: Cell apoptosis increased with aging: 4.38 +/- 1.06 in the adult, 9.38 +/- 1.69 in the elderly and 18.50 +/- 1.60 in the aged group, while the CO content decreased with aging: 12.19 +/- 0.87 in the adult, 7.93 +/- 0.63 in the elderly and 5.68 +/- 0.62 in the aged group, both with statistically significant differences among the 3 groups (P < 0.05). The change of cell apoptosis showed a good negative correlation with that of the CO content (r = -0.889, P < 0.01). CONCLUSION: Cell apoptosis and CO content change in the penile tissue of aging rats, and CO may participate in the development of ED by regulating cell apoptosis.

Intervention effects of ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of neurotrophin-4 and N-cadherin.

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg(2+) free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg(2+) free medium for 3 hours), iii) GLS group I (incubated with Mg(2+) free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg(2+) free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression.

NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses.

Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder, although the underlying mechanism is unclear. Depressed patients report the alleviation of major depressive disorder symptoms within two hours of a single, low-dose intravenous infusion of ketamine, with effects lasting up to two weeks, unlike traditional antidepressants (serotonin re-uptake inhibitors), which take weeks to reach efficacy. This delay is a major drawback to current therapies for major depressive disorder and faster-acting antidepressants are needed, particularly for suicide-risk patients. The ability of ketamine to produce rapidly acting, long-lasting antidepressant responses in depressed patients provides a unique opportunity to investigate underlying cellular mechanisms. Here we show that ketamine and other NMDAR antagonists produce fast-acting behavioural antidepressant-like effects in mouse models, and that these effects depend on the rapid synthesis of brain-derived neurotrophic factor. We find that the ketamine-mediated blockade of NMDAR at rest deactivates eukaryotic elongation factor 2 (eEF2) kinase (also called CaMKIII), resulting in reduced eEF2 phosphorylation and de-suppression of translation of brain-derived neurotrophic factor. Furthermore, we find that inhibitors of eEF2 kinase induce fast-acting behavioural antidepressant-like effects. Our findings indicate that the regulation of protein synthesis by spontaneous neurotransmission may serve as a viable therapeutic target for the development of fast-acting antidepressants.

Enantioselective fluorescent sensors for amino acid derivatives based on BINOL bearing S-tryptophan unit: synthesis and chiral recognition.

Four novel derivatives of BINOL bearing S-tryptophan unit have been prepared and the structures of these compounds characterized by IR, MS, (1)H and (13)C NMR spectroscopy and elemental analysis. The enantioselective recognition of these receptors has been studied by fluorescence titration and (1)H NMR spectroscopy. The receptors exhibited different chiral recognition abilities towards N-Boc-protected amino acid anions and formed 1:1 complexes between host and guest. Receptors exhibit excellent enantioselective fluorescent recognition ability towards the amino acid derivatives.