Contribution of activating lateral hypothalamus-lateral habenula circuit to nerve trauma-induced neuropathic pain in mice.

Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be targets for the treatment of this disorder.

Measurement of Hyperfine Structure and the Zemach Radius in

We investigate the 2^{3}S_{1}-2^{3}P_{J} (J=0, 1, 2) transitions in ^{6}Li^{+} using the optical Ramsey technique and achieve the most precise values of the hyperfine splittings of the 2^{3}S_{1} and 2^{3}P_{J} states, with smallest uncertainty of about 10 kHz. The present results reduce the uncertainties of previous experiments by a factor of 5 for the 2^{3}S_{1} state and a factor of 50 for the 2^{3}P_{J} states, and are in better agreement with theoretical values. Combining our measured hyperfine intervals of the 2^{3}S_{1} state with the latest quantum electrodynamic (QED) calculations, the improved Zemach radius of the ^{6}Li nucleus is determined to be 2.44(2) fm, with the uncertainty entirely due to the uncalculated QED effects of order mα^{7}. The result is in sharp disagreement with the value 3.71(16) fm determined from simple models of the nuclear charge and magnetization distribution. We call for a more definitive nuclear physics value of the ^{6}Li Zemach radius.

Extrasynaptic CaMKIIα is involved in the antidepressant effects of ketamine by downregulating GluN2B receptors in an LPS-induced depression model.

BACKGROUND: A subanesthetic dose of ketamine provides rapid and effective antidepressant effects, but the molecular mechanism remains elusive. It has been reported that overactivation of extrasynaptic GluN2B receptors is associated with the antidepressant effects of ketamine and the interaction between GluN2B and calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) is important for GluN2B localization and activity. Here, we tested whether changes of CaMKIIα and GluN2B are involved in the antidepressant effects of ketamine. METHODS: Lipopolysaccharide (LPS) was injected intraperitoneally (i.p.) into male C57BL/6 mice. For the interventional study, mice were administrated with ketamine (10 mg/kg, i.p.) or a CaMKIIα inhibitor KN93. Behavioral alterations were evaluated by open-field, novelty-suppressed feeding, and forced-swimming tests. Physiological functions were evaluated by the body weight and fur coat state of mice. The levels of p-CaMKIIα, CaMKIIα, p-GluN2B, GluN2B, p-CREB, CREB, BDNF, GluR1, and GluR2 in the hippocampus were detected by western blotting. The interaction between GluN2B and CaMKIIα was studied using immunoprecipitation assay and small interfering RNA (siRNA) assays. The colocalizations of GluN2B/PSD95 and p-GluN2B/PSD95 were detected by immunofluorescence. The long-term potentiation (LTP) in SC-CA1 of the hippocampus was detected by electrophysiology. RESULTS: LPS injection induced depression-like behaviors, which were accompanied by significant increases in extrasynaptic p-CaMKIIα expression, extrasynaptic GluN2B localization, and phosphorylation and decreases in p-CREB, BDNF, and GluR1 expressions and LTP impairment. These changes were prevented by ketamine administration. Immunoprecipitation assay revealed that LPS induced an increase in the p-CaMKIIα-GluN2B interaction, which was attenuated by ketamine administration. SiRNA assay revealed that CaMKIIα knockdown reduced the level and number of clusters of GluN2B in the cultured hippocampal neurons. KN93 administration also reduced extrasynaptic p-CaMKIIα expression, extrasynaptic GluN2B localization, and phosphorylation and exerted antidepressant effects. CONCLUSION: These results indicate that extrasynaptic CaMKIIα plays a key role in the cellular mechanism of ketamine's antidepressant effect and it is related to the downregulation of extrasynaptic GluN2B localization and phosphorylation.

Dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca2+/calpain might contribute to postoperative cognitive dysfunction in aging mice.

BACKGROUND: Postoperative cognitive decline (POCD) is a recognized clinical phenomenon characterized by cognitive impairments in patients following anesthesia and surgery, yet its underlying mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, learning, and memory via activation of TrkB-full length (TrkB-FL) receptors. It has been reported that an abnormal truncation of TrkB mediated by calpain results in dysregulation of BDNF/TrkB signaling and is associated with cognitive impairments in several neurodegenerative disorders. Calpains are Ca2+-dependent proteases, and overactivation of calpain is linked to neuronal death. Since one source of intracellular Ca2+ is N-methyl-d-aspartate receptors (NMDARs) related and the function of NMDARs can be regulated by neuroinflammation, we therefore hypothesized that dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca2+/calpain might be involved in the pathogenesis of POCD. METHODS: In the present study, 16-month-old C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to establish the POCD animal model. For the interventional study, mice were treated with either NMDAR antagonist memantine or calpain inhibitor MDL-28170. Behavioral tests were performed by open field, Y maze, and fear conditioning tests from 5 to 8 days post-surgery. The levels of Iba-1, GFAP, interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), NMDARs, calpain, BDNF, TrkB, bax, bcl-2, caspase-3, and dendritic spine density were determined in the hippocampus. RESULTS: Anesthesia and surgery-induced neuroinflammation overactivated NMDARs and then triggered overactivation of calpain, which subsequently led to the truncation of TrkB-FL, BDNF/TrkB signaling dysregulation, dendritic spine loss, and cell apoptosis, contributing to cognitive impairments in aging mice. These abnormities were prevented by memantine or MDL-28170 treatment. CONCLUSION: Collectively, our study supports the notion that NMDAR/Ca2+/calpain is mechanistically involved in anesthesia and surgery-induced BDNF/TrkB signaling disruption and cognitive impairments in aging mice, which provides one possible therapeutic target for POCD.

Two new iridoid glycosides from Callicarpa nudiflora.

Two new iridoid glycosides, callicoside E (1) and callicoside F (2), were isolated from the leaves of Callicarpa nudiflora. Their structures were established by one- and two-dimensional NMR spectroscopy and mass spectrometry. In an in vitro bioassay, compounds 1 and 2 showed an pronounced hepatoprotective activity against d-galactosamine-induced toxicity in WB-F344 rat hepatic epithelial stem-like cells.[Formula: see text].

Disruption of Striatal-Enriched Protein Tyrosine Phosphatase Signaling Might Contribute to Memory Impairment in a Mouse Model of Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) is a potentially irreversible acute cognitive dysfunction with unclear mechanism. Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase which normally opposes synaptic strengthening by regulating key signaling molecules involved in synaptic plasticity and neuronal function. Thus, we hypothesized that abnormal STEP signaling pathway was involved in sepsis-induced cognitive impairment evoked by lipopolysaccharides (LPS) injection. The levels of STEP, phosphorylation of GluN2B (pGluN2B), the kinases extracellular signal-regulated kinase 1/2 (pERK), cAMP-response element binding protein (CREB), synaptophysin, brain derived neurotrophic factor (BDNF), and post-synaptic density protein 95 (PSD95) in the hippocampus, prefrontal cortex, and striatum were determined at the indicated time points. In the present study, we found that STEP levels were significantly increased in the hippocampus, prefrontal cortex, and striatum following LPS injection, which might resulted from the disruption of the ubiquitin-proteasome system. Notably, a STEP inhibitor TC-2153 treatment alleviated sepsis-induced memory impairment by increasing phosphorylation of GluN2B and ERK1/2, CREB/BDNF, and PSD95. In summary, our results support the key role of STEP in sepsis-induced memory impairment in a mouse model of SAE, whereas inhibition of STEP may provide a novel therapeutic approach for this disorder and possible other neurodegenerative diseases.

[Study advances in regulation effect of Tripterygium wilfordii and its extracts on innate immune system in rheumatoid arthritis cases].

Rheumatoid arthritis( RA) is an autoimmune disease characterized by chronic and aggressive polyarthritis. The innate immunity mechanism plays a key role in the pathogenesis of RA. Tripterygium wilfordii and its extracts have regulatory effects on innate immune cells including macrophages,dendritic cells,neutrophils,mast cells,NK cells,NKT cells,etc.,as well as a variety of innate immune molecules including cytokines,adhesion molecules,patterns recognition receptor( PRR) and the complement molecules,showing a regulatory effect in the pathogenesis of RA innate immunity. In this paper,the recent domestic and foreign researches on the pathogenesis of RA with innate immunity involved were reviewed and the research status of T. wilfordii and its extracts on the regulation of innate immunity involved in RA was summarized.

Impact of multiple quaternary ammonium salts on dynamic properties of BSA adsorption layer at different pH values.

The interaction mechanism of multiple quaternary ammonium salts (MQAS) with bovine serum albumin (BSA) was examined by the fluorescence quenching method and circular dichroism (CD) spectra. Moreover, the effects of MQAS on the dynamic properties of BSA adsorption layers at different pH values were investigated using dilational interfacial rheology. Results show that the quenching constants increase with an increase in pH values and decrease with an increase in the experiment temperature at pH 5.3. The quenching mechanism is static quenching, and the electrostatic force dominates the interaction between MQAS and BSA at pH 5.3. Due to three positive head groups, MQAS can significantly affect the dynamic interfacial activity of BSA molecules at a relatively low concentration. At pH 4.3, the electrostatic repulsion is unfavorable for the formation of MQAS/BSA complexes. Consequently, MQAS molecules will replace BSA molecules from the interface by competitive adsorption. At the pH value above the isoelectric point of BSA, the electrostatic attraction is better for the formation of MQAS/BSA complexes, which exhibit a rapid adsorption rate and an enhanced interfacial activity. Moreover, the kinetic dependencies of interfacial dilational elasticity for the MQAS/BSA mixtures become nonmonotonous. The appearance of the maximum interfacial elasticity values can be attributed to the formation of tails and loops, which suggests that the addition of MQAS destroys the secondary and tertiary structure of protein in the bulk phase. In addition, the effects of MQAS on the secondary structure of protein were demonstrated by CD spectra.

The potential signaling pathway between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha in renal interstitial fibrosis disease.

Peroxisome proliferator-activated receptorγ (PPARγ) can regulate the process of cell apoptosis and is related to the progression of renal disorders. Retinoic acid receptor alpha (RARα) is one of the nuclear receptors involved in a variety of kidney diseases. Renal interstitial fibrosis (RIF) is a common denominator of chronic kidney disease (CKD). This study investigated whether a potential signaling pathway existed between PPARγ and RARα in RIF rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into four groups: a model group subjected to UUO (GU), and three other groups treated with rosiglitazone sodium (GRS), GW9662 and dimethyl sulfoxide (DMSO), n = 40, respectively. Renal tissues were collected two and four weeks after post-surgery. The relevant indicators were detected. In comparison with the GU group, the expressions of PPARγ and RARα (protein and mRNA) were increased in the GRS group, and decreased in the GW9662 group (all p < 0.01). The RIF index, mRNA and protein expression of transforming growth factor-ß1 (TGF-ß1), and the protein expressions of collagen-IV (Col-IV) and fibronectin (FN) in the GRS group were more markedly reduced than those in the GU group; their levels in the GW9662 group were elevated (all p < 0.01). PPARγ or RARα was negatively correlated to the RIF index, TGF-ß1, Col-IV and FN. PPARγ was positively correlated with RARα (all p < 0.01). In conclusion, PPARγ agonist can elevate the expression of PPARγ or RARα in RIF rats. There might be a potential signaling pathway between PPARγ and RARα in RIF disease.

[Chemical Constituents from Callicarpa nudiflora].

OBJECTIVE: To study the chemical constituents of Callicarpa nudiflora. METHODS: The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. RESULTS: Eleven compounds were isolated from the leaves of Callicarpa nudiflora, whose structures were elucidated as 2α,3α-dihydroxyurs-12-en-28-oic acid (1), isorhamnetin (2), 2α,3ß,19α-trihydroxyurs-12-en-28-oic acid(3), 2α,3α,19α,23-tetrahydroxyurs-12-en-28-oic acid(4), 2α,3α,19α-trihyhydroxy-olean-12-en-28-O-α-D-glucopyranoside (5), benzyl-4'-hydroxy-benzoyl-3'-O-ß-D-glucopyranoside(6) (3S,5R,6R,7E,9S)-megastigman-7-ene-3,5,6,9-tetrol(7), philonotisflavone(8), 1, 6-di-O-caffeoyl-ß-D-glucopyranoside (9), luteolin-4'-O-(6"-E-caffeoyl)-ß-D-glucopyranoside (10), and (6S, 9R)-roseoside(11). CONCLUSION: All compounds are isolated from this plant for the first time.

Akt mediates GSK-3ß phosphorylation in the rat prefrontal cortex during the process of ketamine exerting rapid antidepressant actions.

Ketamine may produce rapid and sustained antidepressant effects. Despite the fact that the detailed underlying mechanism remains unknown, recent studies have suggested the involvement of the mammalian target of rapamycin (mTOR) pathway and glycogen synthase kinase-3 (GSK-3) signal, respectively, in the process of ketamine exerting antidepressant actions. This study aimed to investigate the mechanism by which ketamine phosphorylates GSK-3ß in the rat prefrontal cortex (PFC) via applying vehicle or the antagonists of mTOR signalling pathway proteins including PI3K/Akt, mTOR and p70S6 kinase to the rats in the forced swimming test (FST) prior to ketamine administration, and subsequently observing the levels of phosphorylated GSK-3ß, mTOR and p70S6K in rat PFC as well as the immobility time of rats in the FST. Our results revealed that compared to treatment with vehicle, ketamine increased the levels of phosphorylated GSK-3ß in rat PFC (p < 0.05), which was attenuated by PI3K/Akt antagonist pretreatment (p < 0.05), but could not be affected by mTOR antagonist or p70S6K antagonist pretreatment. In addition, all the antagonists reversed the ketamine-induced increases in the phosphorylation of mTOR and p70S6K (p < 0.05). They also all abolished the rapid-acting antidepressant actions of ketamine demonstrated by the increased immobility time of rats in the FST. In conclusion, Akt mediates the phosphorylation of GSK-3ß in rat PFC during the process of ketamine exerting rapid antidepressant actions.

Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsis-associated encephalopathy.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Low-density solvent-based vortex-assisted surfactant-enhanced emulsification liquid-liquid microextraction and its application.

For the first time, the low-density solvent-based vortex-assisted surfactant-enhanced emulsification liquid-liquid microextraction, followed by GC-flame photometric detection has been developed for the determination of eight organophosphorus pesticides in aqueous samples. A small volume of organic extraction solvent (toluene) was dispersed into the aqueous samples by the assistance of surfactant and vortex agitator. The extraction was performed in a special disposable polyethylene pipette, allowing using the reagents with lower density than water as extraction solvents. The influence parameters were systemically investigated and optimized: toluene (30 µL) and Triton X-100 (0.2 mmol/L) were used as the extraction solvent and the surfactant, respectively, and the extraction was performed for 1 min under room temperature without adding sodium chloride. Under the optimum conditions, the validation parameters such as the RSD (n = 6; 2.1-11.3%), LOD (0.005 and 0.05 µg/L), and linear range (0.1-50.0 µg/L with correlation coefficients (0.9958-0.9992) showed the method was satisfying. The proposed method has been successfully applied to the determination of the organophosphorus pesticides in real samples with recoveries between 82.8 and 100.2%.

Changes in plasma and cerebrospinal fluid biomarkers in aged patients with early postoperative cognitive dysfunction following total hip-replacement surgery.

PURPOSE: We hypothesized that different patterns of biomarkers of brain injury and inflammation exist in aged patients with postoperative cognitive dysfunction (POCD) after total hip-replacement with spinal anesthesia. METHODS: Eighty-three patients older than 65 years undergoing elective total hip-replacement surgery were enrolled in this prospective observational study. The CSF levels of Tau, phosphorylated-tau (pTau), amyloidß1-42 (Aß1-42), Tau/Aß1-42, pTau/Aß1-42, BDNF, IL-6, and IL-1ß were measured preoperatively. Perioperative plasma levels of IL-1ß, IL-6, brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), and malonaldehyde (MDA) as well as neurocognitive tests were determined preoperatively and seven days postoperatively. RESULTS: Sixty-one patients completed both the CSF and blood samples collection and the neurocognitive tests. POCD occurred in 24.6 % of patients at seven days after surgery. Patients with POCD had significantly higher IL-1ß, Tau/Aß1-42, pTau/Aß1-42, and a lower level of Aß1-42 in CSF when compared with the Non-POCD group (P < 0.05). Furthermore, POCD patients displayed significantly higher plasma levels of MDA when compared with Non-POCD patients at seven days after surgery (P < 0.05). There was no difference in preoperative CSF levels of Tau, IL-6, and pTau as well as plasma levels of IL-1ß, IL-6, BDNF and CRP between POCD and Non-POCD groups (P > 0.05). CONCLUSION: The POCD patients were associated with higher postoperative plasma levels of MDA, and higher IL-1ß and lower Aß1-42 levels in preoperative CSF that might predispose the development of POCD in aged patients following total hip-replacement surgery with spinal anesthesia.

Dysfunction of NRG1/ErbB4 Signaling in the Hippocampus Might Mediate Long-term Memory Decline After Systemic Inflammation.

Accumulating evidence has suggested that a great proportion of sepsis survivors suffer from long-term cognitive impairments after hospital discharge, leading to decreased life quality and substantial caregiving burdens for family members. However, the underlying mechanism remains unclear. In the present study, we established a mouse model of systemic inflammation by repeated lipopolysaccharide (LPS) injections. A combination of behavioral tests, biochemical, and in vivo electrophysiology techniques were conducted to test whether abnormal NRG1/ErbB4 signaling, parvalbumin (PV) interneurons, and hippocampal neural oscillations were involved in memory decline after repeated LPS injections. Here, we showed that LPS induced long-term memory decline, which was accompanied by dysfunction of NRG1/ErbB4 signaling and PV interneurons, and decreased theta and gamma oscillations. Notably, NRG1 treatment reversed LPS-induced decreases in p-ErbB4 and PV expressions, abnormalities in theta and gamma oscillations, and long-term memory decline. Together, our study demonstrated that dysfunction of NRG1/ErbB4 signaling in the hippocampus might mediate long-term memory decline in a mouse model of systemic inflammation induced by repeated LPS injections. Thus, targeting NRG1/ErbB4 signaling in the hippocampus may be promising for the prevention and treatment of this long-term memory decline.

A role of GABAA receptor α1 subunit in the hippocampus for rapid-acting antidepressant-like effects of ketamine.

Ketamine can produce rapid-acting antidepressant effects in treatment-resistant patients with depression. Although alterations in glutamatergic and GABAergic neurotransmission in the brain play a role in depression, the precise molecular mechanisms in these neurotransmission underlying ketamine's antidepressant actions remain largely unknown. Mice exposed to FSS (forced swimming stress) showed depression-like behavior and decreased levels of GABA (γ-aminobutyric acid), but not glutamate, in the hippocampus. Ketamine increased GABA levels and decreased glutamate levels in the hippocampus of mice exposed to FSS. There was a correlation between GABA levels and depression-like behavior. Furthermore, ketamine increased the levels of enzymes and transporters on the GABAergic neurons (SAT1, GAD67, GAD65, VGAT and GAT1) and astrocytes (EAAT2 and GAT3), without affecting the levels of enzymes and transporters (SAT2, VGluT1 and GABAAR γ2) on glutamatergic neurons. Moreover, ketamine caused a decreased expression of GABAAR α1 subunit, which was specifically expressed on GABAergic neurons and astrocytes, an increased GABA synthesis and metabolism in GABAergic neurons, a plasticity change in astrocytes, and an increase in ATP (adenosine triphosphate) contents. Finally, GABAAR antagonist bicuculline or ATP exerted a rapid antidepressant-like effect whereas pretreatment with GABAAR agonist muscimol blocked the antidepressant-like effects of ketamine. In addition, pharmacological activation and inhibition of GABAAR modulated the synthesis and metabolism of GABA, and the plasticity of astrocytes in the hippocampus. The present data suggest that ketamine could increase GABA synthesis and astrocyte plasticity through downregulation of GABAAR α1, increases in GABA, and conversion of GABA into ATP, resulting in a rapid-acting antidepressant-like action. This article is part of the Special Issue on 'Ketamine and its Metabolites'.

Dietary pattern interfered with the impacts of pesticide exposure by regulating the bioavailability and gut microbiota.

Dietary intake is an essential way for pesticides to enter the human body. The effects of dietary pattern on the risks of pesticides and what diet can reduce the damage are largely unknown. Here, it is found that Mediterranean diet and Vegetarian diet could alleviate insulin resistance and obesity induced by chlorpyrifos, while Western diet could aggravate that. Gut microbiota and chlorpyrifos bioavailability mediated by the diets were involved in these effects. Both the dietary pattern and chlorpyrifos could change the composition of gut microbiota. Chlorpyrifos caused gut dysbacteriosis which was an important reason for the induced metabolic syndrome. Mediterranean diet and Vegetarian diet could maintain gut microbiota homeostasis and increase intestinal bacteria producing short-chain fatty acids, repair the gut microbiota and intestinal barrier damaged by chlorpyrifos. High dietary fat intake increased the bioavailability of chlorpyrifos, which aggravated the gut dysbacteriosis and destruction of intestinal integrity. Thus, the amount of endotoxin entering the blood increased and caused low-grade inflammation, which was also an important pathway of metabolic syndrome. The results suggested that although it was almost impossible to avoid the exposure to pesticides in modern life, healthy diets could regulate beneficial gut microbiota and alleviate the risk of pesticide exposure.

Vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction for the determination of triazine herbicides in water samples by microemulsion electrokinetic chromatography.

A novel method based on the combination of microemulsion electrokinetic chromatography (MEEKC) and vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction (VSLLME) was developed for the determination of five triazine herbicides (simazine, atrazine, ametryn, prometryn, and terbutryn) in water samples. The five triazine herbicides were baseline separated by using the microemulsion buffer containing a 10 mmol/L borate buffer at pH 9.5, 2.5% (w/v) SDS as surfactant, 0.8% (w/v) ethyl acetate as oil phase, and 6.0% (w/v) 1-butanol as cosurfactant. The optimum extraction conditions of VSLLME were as follows: 100 µL chloroform was used as extraction solvent, 5.0 × 10⁻5 mol/L Tween-20 was chosen as the surfactant to enhance the emulsification, and the extraction process was carried out by vortex mixing for 3 min. Under these optimum experimental conditions, the calibration curve was linear in the range of 2.0-200.0 ng/mL, with the correlation coefficients (r²) varying from 0.9927 to 0.9958. The detection limits of the method varied from 0.41 to 0.62 ng/mL. The purposed method was applied to the determination of five triazine herbicides in real water samples, and the recoveries were between 80.6 and 107.3%.

Tramadol pretreatment enhances ketamine-induced antidepressant effects and increases mammalian target of rapamycin in rat hippocampus and prefrontal cortex.

Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR) in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST). Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

[Determination of six metal elements in animal samples by flame atomic absorption spectrometry with wet digestion].

The contents of 6 metal elements (Ca, Mg, K, Na, Cu and Fe ) were determined in serum, urine, feces and different tissue and organs (heart, kidney, stomach, liver, spleen, intestine and lung) of Wistar rats and mice by flame atomic absorption spectrometry (FAAS) with wet digestion. The samples were digested by the mixture of HNO3 and HClO4 (4 : 1, V/V) at 120 degrees C, the correlation coefficient for the standard curves was 0.999 4-0.999 8, the relative standard deviation (RSD) was from 0.33% to 4.52%, and the recovery for the samples was from 97.7% to 104.2%, meeting the demand of elements content determination in biological samples. The assay method for the determination of the 6 metal elements in animal samples established in this study has the advantages of easy operation, high sensitivity, less sample requiring and accurate results, and the method can be widely used in the determination of various metal elements in biological samples.