Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia.

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.

Extraction of Common Small Microplastics and Nanoplastics Embedded in Environmental Solid Matrices by Tetramethylammonium Hydroxide Digestion and Dichloromethane Dissolution for Py-GC-MS Determination.

Determination of microplastics and nanoplastics (MNPs), especially small MPs and NPs (<150 µm), in solid environmental matrices is a challenging task due to the formation of stable aggregates between MNPs and natural colloids. Herein, a novel method for extracting small MPs and NPs embedded in soils/sediments/sludges has been developed by combining tetramethylammonium hydroxide (TMAH) digestion with dichloromethane (DCM) dissolution. The solid samples were digested with TMAH, and the collected precipitate was washed with anhydrous ethanol to eliminate the natural organic matter. Then, the MNPs in precipitate were extracted by dissolving in DCM under ultrasonic conditions. Under the optimized digestion and extraction conditions, the factors including sizes and concentrations of MNPs showed insignificant effects on the extraction process. The feasibility of this sample preparation method was verified by the satisfactory spiked recoveries (79.6-91.4%) of polystyrene, polyethylene, polypropylene, poly(methyl methacrylate), polyvinyl chloride, and polyethylene terephthalate MNPs in soil/sediment/sludge samples. The proposed sample preparation method was coupled with pyrolysis gas chromatography-mass spectrometry to determine trace small MPs and NPs with a relatively low detection limit of 2.3-29.2 µg/g. Notably, commonly used MNPs were successfully detected at levels of 4.6-51.4 µg/g in 6 soil/sediment/sludge samples. This proposed method is promising for evaluating small solid-embedded MNP pollution.

Receptor-Bound Perfluoroalkyl Carboxylic Acids Dictate Their Activity on Human and Mouse Peroxisome Proliferator-Activated Receptor γ.

In in vitro cell assays, nominal concentrations of a test chemical are most frequently used in the description of its dose-response curves. Although the biologically effective concentration (BEC) is considered as the most relevant dose metric, in practice, it is very difficult to measure. In this work, we attempted to determine the BEC of long-chain perfluoroalkyl carboxylic acids (PFCAs) in peroxisome proliferator-activated receptor γ (PPARγ) activity assays. In both adipogenesis and transcriptional activity assays with human and mouse cells, PPARγ activity of 7 PFCAs first increased and then decreased with their carbon chain length. The binding affinity of these PFCAs with the ligand-binding domain of PPARγ was measured by fluorescence competitive binding assay and showed very poor correlation with their receptor activity (r2 = 0.002-0.047). Internal concentrations of the PFCAs in the cells were measured by LC-MS/MS. Although their correlation with the receptor activity increased significantly, it is still low (r2 = 0.41-0.82). Using the binding affinity constant, internal concentration, and PPARγ concentration measured by immunoassays, concentrations of receptor-bound PFCAs in cells were calculated, which exhibited excellent correlation with PPARγ activity in both adipogenesis and transcriptional activity assays (r2 = 0.91-0.93). These results demonstrate that the concentration of receptor-bound PFCA is the BEC that dictates its activity on human and mouse PPARγ in cell assays. In the absence of any direct detection method, our approach can be used to calculate the target-site concentration of other ligands.

Reversed-phase ion-pair solid-phase extraction and ion chromatography analysis of pyrrolidinium ionic liquid cations in environmental water samples.

A method of reversed-phase ion-pair solid-phase extraction combined with ion chromatography for determination of pyrrolidinium ionic liquid cations (N-methyl-N-ethyl pyrrolidinium, N-methyl-N-propyl pyrrolidinium, and N-methyl-N-butyl pyrrolidinium) in water samples was developed in this study. First, ion-pair reagent sodium heptanesulfonate was added to the water samples after static, centrifugation and filteration. Then, pyrrolidinium cations in the samples were enriched and purified by a reversed-phase solid-phase extraction column, and eluted from the column with methanol aqueous solution as eluent. Finally, the eluate collected was analyzed by ion chromatography. The separation and direct conductivity detection of these pyrrolidinium cations by ion-exchange column using 1.0 mM methanesulfonic acid (in water)/acetonitrile (97:3, v:v) as mobile phase was achieved within 10 min. By using this method, pyrrolidinium cations in Songhua River and Hulan River were successfully extracted with the recoveries ranging from 74.2 to 97.1% and the enrichment factor assessed as 60. Pyrrolidinium cations with the concentration of 0.001-0.03 mg/L can be enriched and detected in the water samples. The developed method for the determination of pyrrolidinium ionic liquid cations in water samples is simple and reliable, which provides a reference for the study of the potential impact of ionic liquids on the environment.

Determination of morpholinium ionic liquid cations in environmental water samples: development of solid-phase extraction method and ion chromatography.

An ion chromatography and solid-phase extraction method has been applied for the separation and detection of morpholinium cations in environmental water samples. The water samples were purified and enriched by a UF-SCX sulfonic acid extraction column and eluted with 0.5 mol L-1 phosphoric acid/sodium dihydrogen phosphate buffer solution/55% methanol. The target compounds were separated on a carboxylic acid cation exchange column with 5.0 mmol L-1 methane sulfonic acid/2% acetonitrile as the mobile phase and direct conductivity detection. The method has been successfully applied to extract morpholinium cations from spiked water samples of Songhua River, Hulan River, East Lake, and Mopanshan Reservoir in China with the recoveries ranging from 75.0% to 98.3%. The relative standard deviations of intraday precision and interday precision are 2.1% and 5.9% or less, respectively. Using this method it is possible to preconcentrate water samples to 0.01-0.04 mg L-1. The results show that the method is applicable to detection of morpholinium ionic liquid cations in environmental water samples and provides a new approach for monitoring ionic liquids in environmental water. Graphical abstract The analysis procedure of morpholinium ionic liquids in environmental water samples.

[Exploration on mechanism of anti-influenza virus activity of genus Paeonia based on network pharmacology].

This paper aimed to investigate the anti-influenza virus activity of the genus Paeonia, screen potential anti-influenza virus compounds and predict targets of anti-influenza virus to explore the mechanism of anti-influenza virus activity. First of all, a total of 301 compounds of the genus Paeonia were summarized from the literatures in recent ten years. The candidate active ingredients from the genus Paeonia were identified by database such as PubChem and Chemical Book. The ligands were constructed by ChemDraw, Avogadro and Discovery Studio Visualizer. Secondly, 23 potential anti-influenza virus targets were developed by combining the target database and the literatures. Uniprot database was used to find the anti-influenza virus targets, and RCSB was used to identify targets associated with anti-influenza virus activity as docked receptor proteins. QuickVina 2.0 software was used for molecular docking. Finally, the Cytoscape 3.5.1 software was used to map the potential activity compounds of the genus Paeonia against influenza virus and the anti-influenza virus target network. Uniprot online database was used to analyze the target GO enrichment and KEGG metabolic pathways. The results showed that 74 compounds of the genus Paeonia had anti-influenza virus effect and 18 potential anti-influenza virus targets were screened. GO analysis concluded that the mechanism of the genus Paeonia anti-influenza virus is consistent with the mechanism of NA anti-influenza virus in order to stop the sprouting, dispersion and diffusion of virus and reduce the ability of virus to infect, so that the infection can be restricted so as to achieve the anti-influenza virus effect.

Identification of protein tyrosine phosphatase SHP-2 as a new target of perfluoroalkyl acids in HepG2 cells.

Perfluoroalkyl acids (PFAAs) are widespread environmental contaminants which have been detected in humans and linked to adverse health effects. Previous toxicological studies mostly focused on nuclear receptor-mediated pathways and did not support the observed toxic effects. In this study, we aimed to investigate the molecular mechanisms of PFAA toxicities by identifying their biological targets in cells. Using a novel electrochemical biosensor, 16 PFAAs were evaluated for inhibition of protein tyrosine phosphatase SHP-2 activity. Their potency increased with PFAA chain length, with perfluorooctadecanoic acid (PFODA) showing the strongest inhibition. Three selected PFAAs, 25 µM perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid, and PFODA, also inhibited SHP-2 activity in HepG2 cells and increased paxillin phosphorylation level. PFOA was detected in the immunoprecipitated SHP-2 from the cells exposed to 250 µM PFOA, providing unequivocal evidence for the direct binding of PFOA with SHP-2 in the cell. Molecular docking rationalized the formation of PFAA/SHP-2 complex and chain length-dependent inhibition potency. Our results have established SHP-2 as a new cellular target of PFAAs.

Development and validation of the Social Touch Experiences and Attitudes Questionnaire-Chinese version (STEAQ-C): How interpersonal touch relates to subclinical traits and symptoms.

Social touch has a vital role in human development and psychological well-being. However, there is a lack of measures assessing individual differences in social touch experiences and attitudes, especially under Eastern cultures. This study developed the Social Touch Experiences and Attitudes Questionnaire - Chinese version (STEAQ-C) and examined its psychometric properties with healthy young Chinese adults. In Study 1, an item pool was generated and principal component analysis (PCA) was used to identify the factor structure of the STEAQ. Study 2 recruited an independent sample and examined its reliability and validity. Network analysis further explored the interrelations between social touch and a variety of subclinical traits and symptoms. PCA identified four factors of the STEAQ-C, relating to childhood touch experiences, current touch with intimate partners, with family and friends, and with unfamiliar people. Study 2 confirmed the four-factor structure and upheld its internal consistency and stability. Positive attitudes towards and greater experiences of social touch were negatively correlated with sensory over-responsiveness and sensory hyposensitivity, as well as childhood trauma particularly emotional neglect, supporting the convergent validity. Evidence of criterion-related validity was accrued via its concurrent and predictive associations with secure attachment style, higher levels of social competence, and lower levels of social anxiety. Network analysis highlighted altered perception of social touch may be a shared feature for psychiatric conditions with social dysfunctions (e.g., autism, social anxiety and negative schizotypy). The newly-developed STEAQ-C may be a timely tool in assessing social touch experiences and attitudes under Eastern cultures.

Hydroxyl-containing triazine-based conjugated microporous polymers for solid phase extraction of fluoroquinolone antibiotics in the environment and food samples.

Fluoroquinolones (FQs) are a category of broadly used antibiotics. Development of an effective and sensitive approach for determination of trace FQs in environmental and food samples is still challenging. Herein, the hydroxyl-containing triazine-based conjugated microporous polymers (CMPs-OH) was constructed and served as SPE absorbent for the efficient enrichment of FQs. Based on DFT simulations, the excellent enrichment capacity between CMPs-OH and FQs was contributed by hydrogen bonding and π-π interactions. In combination with high-performance liquid chromatography-tandem mass spectrometry, the proposed approach exhibited a wide linear range (0.2-400 ng L-1), low detection limits (0.05-0.15 ng L-1), and good intraday and interday precisions under optimal conditions. In addition, the established method was effectively utilized for the determination of FQs in fourteen samples with recoveries between 82.6 % and 109.2 %. This work provided a feasible sample pretreatment method for monitoring FQs in environmental and food matrices.

Corticotropin-releasing hormone neurons control trigeminal neuralgia-induced anxiodepression via a hippocampus-to-prefrontal circuit.

Anxiety and depression are frequently observed in patients suffering from trigeminal neuralgia (TN), but neural circuits and mechanisms underlying this association are poorly understood. Here, we identified a dedicated neural circuit from the ventral hippocampus (vHPC) to the medial prefrontal cortex (mPFC) that mediates TN-related anxiodepression. We found that TN caused an increase in excitatory synaptic transmission from vHPCCaMK2A neurons to mPFC inhibitory neurons marked by the expression of corticotropin-releasing hormone (CRH). Activation of CRH+ neurons subsequently led to feed-forward inhibition of layer V pyramidal neurons in the mPFC via activation of the CRH receptor 1 (CRHR1). Inhibition of the vHPCCaMK2A-mPFCCRH circuit ameliorated TN-induced anxiodepression, whereas activating this pathway sufficiently produced anxiodepressive-like behaviors. Thus, our studies identified a neural pathway driving pain-related anxiodepression and a molecular target for treating pain-related psychiatric disorders.

Preparation of a chitosan-coated C(18)-functionalized magnetite nanoparticle sorbent for extraction of phthalate ester compounds from environmental water samples.

Novel superparamagnetic chitosan-coated C(18)-functionalized magnetite nanoparticles (MNPs) were successfully synthesized and applied as an effective sorbent for the preconcentration of several typical phthalate ester compounds from environmental water samples. The MNPs were 20 nm in diameter and had a high magnetic saturation value (52 emu g(-1)), which endowed the sorbent with a large surface area and the convenience of isolation from water samples. Phthalate esters could be extracted by the interior octadecyl groups through hydrophobic interaction. The hydrophilic porous chitosan polymer coating promoted the dispersion of MNPs in water samples, and improved the anti-interference ability of the sorbent without influencing the adsorption of analytes. The main factors affecting the adsorption of phthalate esters, including the pH of the solution, humic acid, sample loading volume, adsorption time, and desorption conditions, were investigated and optimized. Under the conditions selected (pH 11, adsorption time 20 min, elution with 10 mL of acetonitrile, and concentration to 0.5 mL), concentration factors of 1,000 were achieved by extracting 500 mL of several environmental water samples with 0.1 g of MNP sorbent. The method detection limits obtained for di-n-propyl phthalate, di-n-butyl phthalate, dicyclohexyl phthalate, and di-n-octyl phthalate were 12.3, 18.7, 36.4, and 15.6 ng L(-1), respectively. The recoveries of spiked samples ranged from 60 to 100%, with a low relative standard deviation (1-8%), which indicated good method precision.

Plasma degradation of Cationic Blue dye with contact glow discharge electrolysis.

Contact glow discharge electrolysis (CGDE) of Cationic Blue SD-GTL (CB) was investigated by determining degradation rates and rate constants under different voltages, pH, temperature and initial concentrations. The results indicated that 500 V was the optimum voltage for CGDE of CB under experimental conditions. The effect of pH was not appreciable. Fe²(+) and Fe³(+) had a remarkable catalytic effect on the degradation of CB. The degradation rate was up to 99.7% after 3 minutes CGDE treatment when the concentration of Fe²(+) was 20.0 mg/L. And when the concentration of Fe³ (+) was 5.0 mg/L, the degradation rate was only 68.6% after 10 minutes CGDE treatment. The reaction mechanisms were also well illustrated by relative reactions and their rate constants. It had been demonstrated that CB underwent oxidative degradation in CGDE.

Activation of ventrolateral orbital cortex improves mouse neuropathic pain-induced anxiodepression.

Depression and anxiety are frequently observed in patients suffering from neuropathic pain. The underlying mechanisms remained unclear. The ventrolateral orbital cortex (VLO) has attracted considerable interest in its role in antidepressive effect in rodents. In the present study, we further investigated the role of the VLO in the anxiodepressive consequences of neuropathic pain in a chronic constriction injury of infraorbital nerve-induced trigeminal neuralgia (TN) mouse model. Elevated plus maze, open field, forced swimming, tail suspension, and sucrose preference tests were used to evaluate anxiodepressive-like behaviors. The results show that chemogenetic activation of bilateral VLO neurons, especially CaMK2A+ pyramidal neurons, blocked the TN-induced anxiodepressive-like behaviors. Chemogenetic and optogenetic activation of VGLUT2+ or inhibition of VGAT+ VLO neurons was sufficient to produce an antianxiodepressive effect in TN mice. Pharmacological activation of D1-like receptors (D1Rs) but not D2Rs in the VLO significantly alleviated TN-induced depressive-like behaviors. Electrophysiological recordings revealed a decreased excitability of VLO excitatory neurons following neuropathic pain. Furthermore, activation of submedius thalamic nucleus-VLO (Sm-VLO) projection mimicked the antianxiodepressive effect of VLO excitation. Conversely, activation of VLO-periaqueductal gray matter (PAG) projection had no effect on TN-induced anxiodepressive behaviors. This study provides a potentially novel mechanism-based therapeutic strategy for the anxiodepressive consequences of neuropathic pain.

A new solid-phase extraction disk based on a sheet of single-walled carbon nanotubes.

A new kind of solid-phase extraction disk based on a sheet of single-walled carbon nanotubes (SWCNTs) is developed in this study. The properties of such disks are tested, and different disks showed satisfactory reproducibility. One liter of aqueous solution can pass through the disk within 10-100 min while still allowing good recoveries. Two disks (DD-disk) can be stacked to enrich phthalate esters, bisphenol A (BPA), 4-n-nonylphenol (4-NP), 4-tert-octylphenol (4-OP) and chlorophenols from various volumes of solution. The results show that SWCNT disks have high extraction ability for all analytes. The SWCNT disk can extract polar chlorophenols more efficiently than a C(18) disk from water solution. Unlike the activated carbon disk, analytes adsorbed by the new disks can be eluted completely with 8-15 mL of methanol or acetonitrile. Finally, the DD-disk system is used to pretreat 1000-mL real-world water samples spiked with BPA, 4-OP and 4-NP. Detection limits of 7, 25, and 38 ng L(-1) for BPA, 4-OP, and 4-NP, respectively, were achieved under optimized conditions. The advantages of this new disk include its strong adsorption ability, its high flow rate and its easy preparation.

Determination of sulfonamide compounds in sewage and river by mixed hemimicelles solid-phase extraction prior to liquid chromatography-spectrophotometry.

Mixed hemimicelles-based solid-phase extraction was investigated for the preconcentration of five sulfonamides from environmental water samples prior to HPLC-spectrophotometry determination in this paper. A comparative study on the use of sodium dodecyl sulfate (SDS) coating gamma-alumina or octadecyltrimethylammonium bromide (OTMABr) and OTMABr coating silica as sorbent materials were presented. The five analytes (sulfadiazine (SDA), sulfathiazole (STA), sulfapyridine (SPD), sulfamethazine (SMZ) and sulfamethoxazole (SMX)) were quantitatively adsorbed on OTMABr-gamma-alumina and OTMABr-silica mixed hemimicelles, but OTMABr-gamma-alumina was not adopted because it worked at a high pH (around 10), instead, OTMABr-silica was selected to overcoming the pH restriction. The analytes retained on the cartridge were quantitatively desorbed with suitable amounts of methanol. Factors influencing the extraction efficiency, such as the amount of surfactant, pH of sample and breakthrough volume were discussed. The proposed method had been applied to determining the five sulfonamides in several environmental water samples and concentration factors of 300 and 600 for SDA and other four analytes were achieved, respectively. Detection limits obtained ranged between 0.15 and 0.35microg/L for this five sulfonamides under the optimized conditions. The accuracy of the method was evaluated by recovery measurements on spiked samples, and good recovery results (89-113%) with precision of 3-6% were achieved.

Cloud point extraction coupled with HPLC-UV for the determination of phthalate esters in environmental water samples.

A method based on cloud point extraction was developed to determine phthalate esters including di-ethyl-phthalate (DEP), di-(2-ethylhexyl)-phthalate (DEHP) and di-cyclohexyl-phthalate (DCP) in environmental water samples using high-performance liquid chromatography separation and ultraviolet detection (HPLC-UV). The non-ionic surfactant Triton X-114 was chosen as extraction solvent. The parameters affecting extraction efficiency, such as concentrations of Triton X-114 and Na2SO4, equilibration temperature, equilibration time and centrifugation time were evaluated and optimized. Under the optimum conditions, the method can achieve preconcentration factors of 35, 88, 111 and detection of limits of 2.0, 3.8, 1.0 ng/ml for DEP, DEHP and DCP in 10-ml water sample, respectively. The proposed method was successfully applied to the determination of trace amount of phathalate esters in effluent water of the wastewater treatment plant and the lixivium of plastic fragments.

Multi-walled carbon nanotubes as a solid-phase extraction adsorbent for the determination of chlorophenols in environmental water samples.

Multi-walled carbon nanotubes (MWCNs) are used as adsorbent for solid-phase extraction (SPE) of several chlorophenols (CPs). CPs were adsorbed on MWCNs cartridge, then desorbed with pH 10.0 methanol, finally determined by HPLC. Under the optimized conditions, detection limits of 0.08-0.8 ng mL(-1) were obtained. The method had been applied to analyze the five CPs in tap water and river water.

Trace analysis of sulfonylurea herbicides in water by on-line continuous flow liquid membrane extraction--C18 precolumn liquid chromatography with ultraviolet absorbance detection.

An on-line system that consists of continuous-flow liquid membrane extraction (CFLME), C18 precolumn, and liquid chromatography with UV detection was applied to trace analysis of sulfonylurea herbicides in water. During preconcentration by CFLME, five target compounds, including metsulfuron methyl, bensulfuron methyl, tribenuron methyl, sulfometuron methyl, and ethametsulfuron, were enriched in 960 microl of 0.5 mol l(-1) Na2CO3-NaHCO3 (pH 10.8) buffer used as acceptor. This acceptor was on-line neutralized and transported to the C18 precolumn where the analytes were absorbed and focused. Then the focused analytes were injected onto a C18 analytical column for separation and detection at 240 nm. The proposed method was applied to determine sulfonylurea herbicides in water, river, and reservoir water with detection limits of 10-50 ng l(-1) when enriching a 120-ml sample. Throughput is typically one sample per hour.

Determination of sulfonylurea herbicides by continuous-flow liquid membrane extraction on-line coupled with high-performance liquid chromatography.

On-line coupling continuous-flow liquid membrane extraction (CFLME) with HPLC, a novel automatic system was developed for the determination of sulfonylurea herbicides in water. After an automatic trace-enrichment process by CFLME, which is the combination of continuous flow liquid-liquid extraction and support liquid membrane (SLM) extraction, the target analytes were concentrated in 50 microl of 0.2 M Na2CO3-NaHCO3 (pH 10.0) buffer. The concentrated sample solutions were injected directly onto a C18 analytical column with a valve, and detected at 240 nm with a diode array detector. Metsulfuron methyl (MSM), and DPX-A 7881 were baseline separated with a mobile phase consisting of methanol and 67 mM KH2PO4-Na2HPO4 (pH 5.91) buffer (45+55, v+v) at a flow-rate of 1.0 ml min(-1). With an enrichment time of 10 min and enrichment sample volume of 20 ml, the enrichment factors and detection limits are 100 and 0.05 microg l(-1) for MSM, and 96 and 0.1 microg l(-1) for DPX-A 7881, respectively. The linear range and precision (RSD) are 0.1-50 microg l(-1) and 7.0% for MSM, and 0.2-50 microg l(-1) and 9.2% for DPX-A 7881, respectively. This proposed method was applied to determine MSM and DPX-A 7881 in seawater, tap water, and bottled mineral water with spiked recoveries in the range of 83-95% for MSM and 88-100% for DPX-A 7881, respectively.