Antioxidant properties of flavonoid derivatives and their hepatoprotective effects on CCl4 induced acute liver injury in mice

Excessive accumulation of free radicals in the body can cause liver damage, aging, cancer, stroke, and myocardial infarction. Anastatin B, a skeletal flavonoid, was reported to have antioxidant and hepatoprotective effects. Anastatin B derivatives, compound 1 and 2, were synthesized by our group previously. In this study, their antioxidant activity and hepatoprotective mechanism were studied using chemical evaluation methods, a cellular model of hydrogen peroxide (H₂O₂)-induced oxidative damage, and a mouse model of carbon tetrachloride (CCl₄)-induced liver injury. Results from the chemical evaluation suggested that both compounds had good antioxidant power and radical scavenging ability in vitro. MTT assay showed that both compounds had cytoprotective activity in H₂O₂-treated PC12 cells. Moreover, their hepatoprotective activities evaluated using a mouse model of CCl₄-induced liver injury that compared with the model group, pretreatment with compound 1 and 2 significantly decreased alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels; reduced the liver tissue damage; and increased glutathione content. However, compound 2 was a more effective hepatoprotectant than compound 1 was. Finally, the amount of TNF-α and cytochrome P450 2E1 (CYP2E1) were significantly downregulated in compound 1 and 2 pretreatment groups. Collectively, our findings demonstrate that both compounds have potential antioxidant activity and hepatoprotective effect in vitro and in vivo. Further chemo-biological study and investigation of the compounds'' enzymatic targets are ongoing.

Excessive accumulation of free radicals in the body can cause liver damage, aging, cancer, stroke, and myocardial infarction.     

Glutamine Improves Innate Immunity and Prevents Bacterial Enteroinvasion During Parenteral Nutrition

Background: Patients receiving parenteral nutrition (PN) are at increased risk of infectious complications compared with enteral feeding, which is in part explained by impaired mucosal immune function during PN. Adding glutamine (GLN) to PN has improved outcome in some clinical patient groups. Although GLN improves acquired mucosal immunity, its effect on innate mucosal immunity (defensins, mucus, lysozymes) has not been investigated. Methods: Forty‐eight hours following venous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 10), PN (n = 12), or PN + GLN (n = 13) for 5 days. Small intestine tissue and luminal fluid were collected for mucin 2 (MUC2), lysozyme, cryptdin 4 analysis, and luminal interleukin (IL)–4, IL‐10, and IL‐13 level measurement. Tissue was also harvested for ex vivo intestinal segment culture to assess tissue susceptibility to enteroinvasive Escherichia coli. Results: In both luminal and tissue samples, PN reduced MUC2 and lysozyme (P < .0001, respectively) compared with chow, whereas GLN addition increased MUC2 and lysozyme (luminal, P < .05; tissue, P < .0001, respectively) compared with PN alone. PN significantly suppressed cryptdin 4 expression, while GLN supplementation significantly enhanced expression. IL‐4, IL‐10, and IL‐13 decreased significantly with PN compared with chow, whereas GLN significantly increased these cytokines compared with PN. Functionally, bacterial invasion increased with PN compared with chow (P < .05), while GLN significantly decreased enteroinvasion to chow levels (P < .05). Conclusions: GLN‐supplemented PN improves innate immunity and resistance to bacterial mucosal invasion lost with PN alone. This work confirms a clinical rationale for providing glutamine for the protection of the intestinal mucosa.     

肿瘤患者偏移的T细胞TCRBV表达谱在自体CIK细胞中的恢复

目的 研究肿瘤患者自体PBMC经体外诱导培养的CIK细胞群TCRBV亚家族表达的变化.方法 Ficoll密度梯度离心法分类人体外周血单核细胞(PBMC),经IFN-γ、OKT-3以及IL-2诱导培养,Trizol试剂提取总RNA,RT-PCR半定量分析24个TCRBV亚家族表达情况,流式分选平台分选CD3+ CD8+细胞和CD3+ CD56+细胞亚群.结果 诱导培养后的CIK中,分化的CD3+ CD56+细胞亚群比例占12.6％～41.7％.PBMC中弱表达或缺失的TCRBV亚家族,在CIK中上调或恢复表达.CIK细胞群中,CD3+CD8+细胞和CD3+ CD56+细胞亚群克隆组成无明显差异.结论 肿瘤患者自体PBMC体外诱导培养CIK细胞后,部分表达偏移的TCRBV亚家族能恢复表达,表明部分受损或被抑制的T细胞克隆在CIK培养中被激活并增殖.     

血管紧张素Ⅱ对心脏成纤维细胞TRPM7通道功能的影响

目的:研究心脏成纤维细胞(CFs)膜上的TRPM7通道的电生理特性。方法:将分离培养出来的乳鼠CFs用6种不同浓度的血管紧张素Ⅱ(AngⅡ)干预至12h,分别测量各组胶原蛋白的表达水平,从而挑选出最佳诱导纤维化的AngⅡ浓度,最佳浓度的AngⅡ分别将CFs干预至5个不同的时间,记录相应的CFs膜上的TRPM7电流及各组的胶原蛋白水平。结果:诱导心脏纤维化最大的AngⅡ浓度是1nmol/L,最佳诱导纤维化浓度干预0,6,12,24,48h后CFs的TRPM7与胶原蛋白Ⅲ的表达水平最初升高,于12h达到最高水平,之后呈现递减水平,且在CFs膜上记录到的TRPM7内外向电流也呈现相应的先增加后降低趋势,与两种蛋白的表达水平正相关。结论:CFs膜上的TRPM7电流在AngⅡ的作用下,呈现先增加后减少的趋势,是AngⅡ介导CFs增殖与凋亡从而导致心脏纤维化的重要途径之一。     

Interface studies of well-controlled polymer bilayers and field-effect transistors prepared by a mixed-solvent method

The properties of semiconductor/dielectric interfaces are crucial to the performance of polymer field-effect transistors. The key to fabricating high-performance polymer transistors by spin-coating is solving solvent corrosion issues, wherein the solvent of the top polymer produces a rough interface or damage on the underlying polymer layer during deposition. Herein, we propose a mixed-solvent method that employs a mixture of an orthogonal solvent of the underlying polymer and a good solvent of the top polymer as the solvent of the top polymer to prepare polymer bilayers and produce a comparative study of the trap density at the semiconductor/dielectric interface of the corresponding transistor. By changing the ratio of orthogonal solvent to good solvent, namely the degree of orthogonality of the mixed solvent with respect to the underlying polymer, the interface and film qualities of polymer bilayers can be well controlled. We applied this method to spin-coat poly(3-hexylthiophene) (P3HT) on poly(methylmethacrylate) (PMMA) with a mixture of cyclohexane (orthogonal solvent) and chloroform (good solvent). The results of morphology characterizations and electrical property studies indicate the optimal ratio of cyclohexane to chloroform for preparing high-quality P3HT/PMMA bilayers for field-effect conduction is 7 : 3. Transistors based on the optimal bilayers with a bottom-gate/top-contact configuration and a long channel length show good performance. The trap density at the P3HT/PMMA interface is evaluated to be 3.6 × 10¹² cm⁻² eV⁻¹ from the subthreshold swing, characterizing the distribution of the interface trap levels across the bandgap in P3HT. Furthermore, based on deviations from ideality in the capacitance–voltage characteristics of the metal–insulator–semiconductor capacitor in the device, the traps at the interface are found to be acceptor-type, with the trap density determined to be 2.3 × 10¹¹ cm⁻². This value is in a good agreement with that estimated from the subthreshold swing.

A mixture of an orthogonal solvent of the bottom polymer and a good solvent of the top polymer is used as the solvent of the top layer to prepare polymer bilayers. The trap densities at the semiconductor/dielectric interface of the corresponding transistor are evaluated.     

Evidence for Elizabethkingia anophelis Transmission from Mother to Infant,Hong Kong

Elizabethkingia anophelis, recently discovered from mosquito gut, is an emerging bacterium associated with neonatal meningitis and nosocomial outbreaks. However, its transmission route remains unknown. We use rapid genome sequencing to investigate 3 cases of E. anophelis sepsis involving 2 neonates who had meningitis and 1 neonate’s mother who had chorioamnionitis. Comparative genomics revealed evidence for perinatal vertical transmission from a mother to her neonate; the 2 isolates from these patients, HKU37 and HKU38, shared essentially identical genome sequences. In contrast, the strain from another neonate (HKU36) was genetically divergent, showing only 78.6% genome sequence identity to HKU37 and HKU38, thus excluding a clonal outbreak. Comparison to genomes from mosquito strains revealed potential metabolic adaptations in E. anophelis under different environments. Maternal infection, not mosquitoes, is most likely the source of neonatal E. anophelis infections. Our findings highlight the power of genome sequencing in gaining rapid insights on transmission and pathogenesis of emerging pathogens.     

Biological efficacy and toxic effect of emergency water disinfection process based on advanced oxidation technology

An innovative and removable water treatment system consisted of strong electric field discharge and hydrodynamic cavitation based on advanced oxidation technologies was developed for reactive free radicals producing and waterborne pathogens eliminating in the present study. The biological efficacy and toxic effects of this advanced oxidation system were evaluated during water disinfection treatments. Bench tests were carried out with synthetic microbial-contaminated water, as well as source water in rainy season from a reservoir of Dalian city (Liaoning Province, China). Results showed that high inactivation efficiency of Escherichia coli (>5 log) could be obtained for synthetic contaminated water at a low concentration (0.5–0.7 mg L^?1) of total oxidants in 3–10 s. The numbers of wild total bacteria (108 × 10³ CFU mL^?1) and total coliforms (260 × 10² MPN 100 mL^?1) in source water greatly reduced to 50 and 0 CFU mL^?1 respectively after treated by the advanced oxidation system, which meet the microbiological standards of drinking water, and especially that the inactivation efficiency of total coliforms could reach 100 %. Meanwhile, source water qualities were greatly improved during the disinfection processes. The values of UV₂₅₄ in particular were significantly reduced (60–80 %) by reactive free radicals. Moreover, the concentrations of possible disinfection by-products (formaldehyde and bromide) in treated water were lower than detection limits, indicating that there was no harmful effect on water after the treatments. These investigations are helpful for the ecotoxicological studies of advanced oxidation system in the treatments of chemical polluted water or waste water. The findings of this work suggest that the developed water treatment system is ideal in the acute phases of emergencies, which also could offer additional advantages over a wide range of applications in water pollution control.     

Theoretical investigations on azole-fused tricyclic 1,2,3,4-tetrazine-2-oxides

Fused compounds, a unique class of large conjugate structures, have emerged as prime candidates over traditional nitrogen-rich mono-ring or poly-ring materials. Meanwhile, compounds containing catenated nitrogen chains have also attracted attention from scientists due to their high heats of formation. On the other hand, the azoxy [–N N(O)–] moiety has been found to increase density effectively in the molecular structure of compounds. Therefore, combining fused heterocyclic organic skeletons with the azoxy moiety can be regarded as an effective method for increasing the density and heat of formation, which results in substantial increase in detonation properties. Based on the above-mentioned considerations, in this study, a series of new non-hydrogen-containing 5/6/5 fused ring molecules with azoxy moiety structures are designed. Furthermore, their properties as potential high-energy-density materials, including their density, heats of formation, detonation properties, and impact sensitivity, have been extensively evaluated using thermodynamic calculations and density functional theory. Among the investigated compounds, 1,3,8,10-tetranitrodiimidazo[1,5-d:5′,1′-f][1,2,3,4]tetrazine 5-oxide (B), 1,10-dinitrobis([1,2,3]triazolo)[1,5-d:5′,1′-f][1,2,3,4]tetrazine 5-oxide (C) and 2,9-dinitrobis([1,2,4]triazolo)[1,5-d:5′,1′-f][1,2,3,4]tetrazine 5-oxide (D) display remarkable stabilities and are predicted to be high-performance energetic materials due to their high density (>1.94 g cm⁻³), detonation velocity (>9616 m s⁻¹), and detonation pressure (>41.1 GPa). In addition, our design strategy, which combines the azoxy moiety and fused tricyclic skeleton to construct nitrogen-rich molecular structures with high density and positive heat of formation, is a valuable approach for developing novel high-energy-density materials with excellent performance and stability.

In this work, a series of novel non-hydrogen-containing 5/6/5 fused ring molecules with azoxy moiety were designed, some physicochemical or detonation properties of them were calculated.     

Venous thromboembolism in non-COVID-19 population during the pandemic: a nationwide multicenter retrospective survey

Journal of Thrombosis and Thrombolysis - Although mechanical thrombectomy is a powerful predictor of stroke outcome, it induces vessel wall injury in the acute phase. This study aimed to analyze...     

临床药师参与治疗鲍曼不动杆菌颅内感染患儿的药学实践

目的为临床救治重症难治性鲍曼不动杆菌颅内感染患儿提供用药参考。方法通过分析临床药师参与救治我院1例鲍曼不动杆菌颅内感染患儿提供的药学服务,根据患者的病情变化,临床药师结合药物的药理药化知识,查阅相关文献资料,与临床医师共同协商,制定出最优的药物治疗方案。结果通过临床医师及临床药师的共同努力,最终成功救治该患儿。结论临床药师的参与可以协助医师制订安全、有效的治疗方案。