[Determination of four phenolic endocrine-disrupting chemicals in water by dispersive solid-phase extraction-ultra performance liquid chromatography-tandem mass spectrometry based on metal-organic skeleton porous carbon materials].

Phenolic endocrine-disrupting chemicals (EDCs) are exogenous substances that interfere with the endocrine system and disrupt normal cell functions upon entering a living organism, leading to reproductive and developmental toxicity. Therefore, the development of a rapid and efficient analytical method for detecting phenolic EDCs in environmental waters is crucial. Owing to the low concentration of phenolic EDCs in environmental water, appropriate sample pretreatment methods are necessary to remove interferences caused by the sample matrix and enrich the target analytes before instrumental analysis. Dispersive solid-phase extraction (DSPE) has gained considerable attention as a simple and rapid sample pretreatment method for environmental-sample analysis. In this method, an adsorbent material is uniformly dispersed in a sample solution and the target analytes are extracted through processes such as vortexing. Compared with traditional solid-phase extraction (SPE), DSPE increases the contact area between the adsorbent and sample solution, reduces the required amounts of adsorbent and organic solvents, and improves the extraction efficiency. The adsorbent material plays a critical role in DSPE because it determines the extraction efficiency of the method. Metal-organic frameworks (MOFs) are porous framework materials composed of metal clusters and multifunctional organic ligands. They possess many excellent properties such as tunable pore sizes, large surface areas, and good thermal and chemical stability, rendering them ideal adsorbent materials for sample pretreatment. MOF-derived porous carbon materials obtained through high-temperature carbonization not only increase the density of MOF materials for better separation but also retain the advantages of a large surface area, highly ordered porous structure, and high porosity. In this study, a porous carbon material derived from an MOF, named as University of Oslo-66-carbon (UiO-66-C), was synthesized using a solvothermal method and applied as an adsorbent to enrich four phenolic EDCs (bisphenol A, 4-tert-octylphenol, 4-nonylphenol, and nonylphenol) in water. A method combining DSPE with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established to analyze these phenolic EDCs in water. The UiO-66-C dosage, pH of water sample, adsorption time, eluent type and volume, elution time, and ion strength were optimized. Gradient elution was performed using methanol-water as the mobile phase. The target analytes were separated on an ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and multiple reaction monitoring (MRM) was conducted in negative electrospray ionization mode. The method exhibited a linear correlation within the range of 0.5-100 µg/L for the four phenolic EDCs. The limits of detection (LODs) and quantification (LOQs) of the four phenolic EDCs were 0.01-0.13 µg/L and 0.03-0.42 µg/L, respectively. The precision of the method was evaluated through intra- and inter-day relative standard deviations (RSDs), with values ranging from 1.5% to 10.6% and from 6.1% to 13.2%, respectively. When applied to the detection of phenolic EDCs in tap and surface water, the spiked recoveries of the four phenolic EDCs were 77.1%-116.6%. Trace levels of 4-nonylphenol and nonylphenol were detected in surface water at levels of 1.38 and 0.26 µg/L, respectively. The proposed method exhibits good accuracy and precision; thus, it provides a new rapid, efficient, and sensitive approach for the detection of phenolic EDCs in environmental water.

Pregabalin can interact synergistically with Kv7 channel openers to exert antinociception in mice.

Chronic pain is a common public health problem and remains an unmet medical need. Currently available analgesics usually have limited efficacy for the treatment of chronic pain, including neuropathic pain and persistent inflammatory pain, or they are accompanied by many adverse side effects. The voltage-gated calcium channel blocker (pregabalin) and potassium channel openers (flupirtine and retigabine) have been widely used for the management of chronic pain, but their effectiveness in combination is unclear. In this research, we evaluated the antinociceptive effects of pregabalin in combination with flupirtine or retigabine in carrageenan-induced inflammatory pain and paclitaxel-induced peripheral neuropathy in mice using the von Frey test. Isobolographic analysis indicated that pregabalin exerted synergistic antinociceptive effects when combined with flupirtine or retigabine in neuropathic and inflammatory pain models. Furthermore, the antinociceptive effects of pregabalin, flupirtine/retigabine, and their combinations were significantly attenuated by the Kv7 channel blocker XE991. The favored dose ratio between pregabalin and flupirtine/retigabine in combinations was also investigated. Finally, we evaluated the motor coordination of their combinations using the rotarod test, and the outcomes underpinned their safety. Collectively, our results support the potential use of pregabalin in combination with flupirtine or retigabine to alleviate chronic pain.

Identification of differentially expressed long non-coding RNAs and messenger RNAs involved with muscle development in Dazu black goats through RNA sequencing.

This study aimed to explore the genetic basis of muscle development in goats. The transcriptome dataset for differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs) of goat muscle at different developmental stages were obtained using RNA-Seq. A total of 447,806,481 and 587,559,465 clean reads in the longissimus dorsi muscle of Dazu black goats between 75d embryonic stage and 1d after birth were generated through Illumina paired-end sequencing, and their mapping rates were 89.82 and 90.99%, respectively. Moreover, 4517 DEGs and 648 DELs were identified, and 4784 lncRNA-mRNA targeting relationships were predicted. Gene function annotation results showed that 4101 DEGs were significantly enriched to 1098 GO terms, and 2014 DEGs were significantly enriched to 40 KEGG pathways, including many GO terms and pathways related to muscle development, such as cell differentiation and Wnt signaling pathway. Then, 10 DELs and 20 DEGs were randomly selected for RT-qPCR verification, and the agreement rate between the verification and RNA-Seq results was 90%, indicating the high reliability of the RNA-Seq data analysis. In conclusion, this study obtained several mRNAs and lncRNAs related to the muscle development of Dazu black goats and identified several targeted regulatory pairs of lncRNA-mRNA. This study may serve as a reference to understand the genetic basis and molecular mechanism of muscle development in goats.