A measurement procedure has been developed for the determination of δ 44/40 Ca and δ 56/54 Fe in geological samples by multi‐collector inductively coupled plasma‐mass spectrometry (MC‐ICP‐MS) and thermal ionisation mass spectrometry (TIMS), combined with a single TODGA resin column for their separation. Using the TODGA resin for separation of geological materials, Fe and Ca ions were eluted by using 8 ml of 1.5 mol l −1 HNO 3 and 8 ml of 2 mol l −1 HCl, respectively, and their recovery was 99.7 ± 0.4% ( n = 3) for the former and 99.4 ± 0.6% ( n = 3) for the latter after removal of matrix and interfering elements using 12 ml of 6 mol l −1 HCl. This procedure was validated by the reference materials AGV‐2, BCR‐2 and BHVO‐2. Their Fe and Ca isotope data were comparable to their literature values, confirming a single column containing TODGA resin can be applied to the separation of Fe and Ca in geological samples for determination of their isotope ratios free of measurement bias.
Objective To establish a method for determination of escitalopram in biological samples by ultrasound-assisted ionic liquid-dispersive liquid-liquid microextraction combined with gas chromatography-tandem mass spectrometry （GC-MS/MS） and provide evidences for forensic determination of cases related to escitalopram. Methods The 1-hexyl-3-methylimidazolium hexafluorophosphate （[C6MIM][PF6]） was selected as an extract solvent to process biological samples. Ultrasound-assisted extraction was used on the samples. Then the samples were detected by GC-MS/MS. Results The linear range of escitalopram in blood and liver were 5.56-1 111.10 ng/mL and 0.025-5.00 mg/g, respectively. The correlation coefficient （r） were greater than 0.999, limit of detection （LOD） were 4.00 ng/mL and 2.00 μg/g, limit of quantitation （LOQ） were 14.00 ng/mL and 6.00 μg/g, respectively. The extraction recovery rates were all greater than 50%, the interday and intraday precision were less than 20%. Escitalopram was detected in blood and liver samples from the actual poisoning case by this method with a content of 1.26 μg/mL and 0.44 mg/g, respectively. Conclusion The ultrasound-assisted ionic liquid-dispersive liquid-liquid microextraction combined with GC-MS/MS is environment friendly, rapid, has good enriching effect and consumes less organic solvent and can be used for forensic determination of escitalopram related cases.分散液液微萃取-气相色谱串联质谱联用法测定生物样品中艾司西酞普兰.目的 建立超声辅助离子液体-分散液液微萃取-气相色谱串联质谱（gas chromatography-tandem mass spectrometry，GC-MS/MS）联用法测定生物样品中艾司西酞普兰的方法，为艾司西酞普兰相关案件的法医学鉴定提供依据。 方法 以1-己基-3-甲基咪唑六氟磷酸盐（[C6MIM][PF6]）离子液体为萃取剂处理生物样品，通过超声辅助萃取，GC-MS/MS法检测。 结果 血液和肝组织中艾司西酞普兰的线性范围分别为5.56~1 111.10 ng/mL和0.025~5.00 mg/g，相关系数（r）均大于0.999，检出限分别为4.00 ng/mL和2.00 μg/g，定量限分别为14.00 ng/mL和6.00 μg/g，提取回收率均大于50%，日内和日间精密度均小于20%。采用本方法从实际中毒案件的血液和肝组织样品中均检出艾司西酞普兰成分，含量分别为1.26 μg/mL和0.44 mg/g。 结论 超声辅助离子液体-分散液液微萃取-GC-MS/MS联用法检测生物样品中艾司西酞普兰，具有环境友好、快速、富集效果好、有机溶剂消耗小的优点，可应用于艾司西酞普兰相关案件的法医学鉴定。.法医毒理学；气相色谱-串联质谱法；艾司西酞普兰；超声辅助离子液体-分散液液微萃取；生物检材.
To investigate the therapeutic effect and primary pharmacological mechanism of Ziyuglycoside I (Ziyu I) on collagen-induced arthritis (CIA) mice. CIA mice were treated with 5, 10, or 20 mg/kg of Ziyu I or 2 mg/kg of methotrexate (MTX), and clinical manifestations, as well as pathological changes, were observed. T cell viability and subset type were determined, and serum levels of transforming growth factor-beta (TGF-β) and interleukin-17 (IL-17) were detected. The mRNA expression of retinoid-related orphan receptor-γt (RORγt) and transcription factor forkhead box protein 3 (Foxp3) in mouse spleen lymphocytes was ascertained by the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Molecular docking was used to detect whether there was a molecular interaction between Ziyu I and protein kinase B (Akt). The activation of mechanistic target of rapamycin (mTOR) in T cells was verified by Western blotting or immunofluorescence. Ziyu I treatment effectively alleviated arthritis symptoms of CIA mice, including body weight, global score, arthritis index, and a number of swollen joints. Similarly, pathological changes of joints and spleens in arthritic mice were improved. The thymic index, T cell activity, and RORγt production of Ziyu I-treated mice were significantly reduced. Notably, through molecular docking, western blotting, and immunofluorescence data analysis, it was found that Ziyu I could interact directly with Akt to reduce downstream mTOR activation and inhibit helper T cell 17 (Th17) differentiation, thereby regulating Th17/regulatory T cell (Treg) balance and improving arthritis symptoms. Ziyu I effectively improves arthritic symptoms in CIA mice by inhibiting mTOR activation, thereby affecting Th17 differentiation and regulating Th17/Treg balance.
Rationale An inductively coupled plasma tandem mass spectrometry (ICP‐MS/MS) instrument can be developed to determine 87 Sr/ 86 Sr ratios with an external precision better than 0.05% relative standard deviation (RSD) in “mass shift” mode without prior Sr purification. Previous studies suggested using CH 3 F, N 2 O, and SF 6 as reaction gases for this method because a better reaction rate can be achieved with Sr + than with O 2 in the reaction cell. However, these gases are not commonly used in general chemistry laboratories, and processes using these gases are difficult to implement quickly due to regulations. We aim to develop a rapid method that can be applied to many samples for the accurate determination of 87 Sr/ 86 Sr isotope ratios with precision below 0.1% RSD (or approximately to the fourth decimal place). Methods We evaluated the accuracy and precision of 87 Sr/ 86 Sr ratios in certified reference materials and different rock types determined using ICP‐MS/MS with O 2 as the reaction gas in comparison with those determined using the multicollector inductively coupled plasma mass spectrometry (MC‐ICP‐MS) method. Results This study showed that by using the ICP‐MS/MS method, the 87 Sr/ 86 Sr ratios of BCR‐2 and BHVO‐2 do not vary significantly with and without prior Sr purification; when the Sr concentration of the measured solution is within the range of 60–350 ng/mL, there is no significant effect on the measured 87 Sr/ 86 Sr ratios. The results also showed that the 87 Sr/ 86 Sr ratios of 23 different rock types measured by ICP‐MS/MS and MC‐ICP‐MS methods agree very well. Conclusions The precision of the 87 Sr/ 86 Sr ratio measured using ICP‐MS/MS varies between 0.0001 and 0.0019 (2SD). This precision is less than that of the MC‐ICP‐MS method but is sufficient for certain applications, such as identifying 87 Sr/ 86 Sr ratios in different rock types. These results suggest that the developed ICP‐MS/MS method has the potential for future studies involving the identification of Sr sources.
Hyperplasia and migration of fibroblast-like synoviocytes (FLSs) are the key drivers in the pathogenesis of rheumatoid arthritis (RA) and joint destruction. Abundant Yes-associated protein (YAP), which is a powerful transcription co-activator for proliferative genes, was observed in the nucleus of inflammatory FLSs with unknown upstream mechanisms. Using Gene Expression Omnibus database analysis, it was found that Salvador homolog-1 (SAV1), the pivotal negative regulator of the Hippo-YAP pathway, was slightly downregulated in RA synovium. However, SAV1 protein expression is extremely reduced. Subsequently, it was revealed that SAV1 is phosphorylated, ubiquitinated, and degraded by interacting with an important serine-threonine kinase, G protein-coupled receptor (GPCR) kinase 2 (GRK2), which was predominately upregulated by GPCR activation induced by ligands such as prostaglandin E
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
