Thermus thermophilus 木糖异构酶与木糖醇的分子对接及模型分析

在1BXB结构基础上, 通过分子对接方法构建木糖异构酶与抑制剂木糖醇的复合物模型, 为合理设计解除木糖醇对木糖异构酶的抑制及进一步揭示木糖醇对该酶抑制机理提供参考.     

高效毛细管电泳法手性分离D-氨基酸取代胸腺五肽类似物的研究

采用高效毛细管电泳法分离两对D-氨基酸取代的胸腺五肽类似物。对影响分离的缓冲液pH值、电泳温度、电泳电压等进行了系统的研究。用含20mmol/L2,6-二甲基-β-环糊精(DM-β-CD),40mmol/L磷酸盐缓冲液(Ⅰ:pH6.03;Ⅱ:pH5.05)作运行缓冲液,柱温15℃,电压20kV,使样品获得基线分离,取得了满意的分离结果。结果显示,两组样品的D-氨基酸取代物均比L-氨基酸取代物出峰早,提示D-氨基酸取代物的电泳移动速度较快,与DM-β-CD的结合稳定性较L-氨基酸取代物弱。     

Quantification of tripdiolide in human whole blood by liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry

A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) assay was developed and validated to determine tripdiolide in human whole blood using dexamethasone acetate as an internal standard (I.S.). Liquid-liquid extraction with ethyl acetate was used to isolate them from the biological matrix. Detection was performed on a mass spectrometer coupled with a negative atmospheric pressure chemical ionization (APCI) in the multiple-reaction monitoring (MRM) mode. The calibration curve was linear (r² = 0.9973) in the concentration range of 0.5-100.0 ng/mL in human whole blood with a lower limit of quantification of 0.5 ng/mL. Intra-day and inter-day relative standard deviations (R.S.D.s) were less than 7.0 and 10.1%, respectively. Extraction recoveries of tripdiolide ranged from 80.5 to 90.1%. This assay can be used to determine trace tripdiolide in human whole blood.     

Simultaneous Determination of Triptolide and Tripdiolide in Extract of Tripterygium wilfordii Hook. f. by LC–APCI-MS

A novel method using liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry in the negative selected ion monitoring mode has been developed and validated for rapid simultaneous determination of triptolide and tripdiolide in the extract of Tripterygium wilfordii Hook. f. The molecular ions m/z [M–H]⁻ 359 and 375 were selected for the quantification in selected ion monitoring mode for triptolide and tripdiolide. Standard calibration curve was linear over the concentration range of 0.12–24 and 0.15–30 μg mL⁻¹ for triptolide and tripdiolide. The relative standard deviations of intra- and inter-day were in the range of 4.7–9.9 and 8.9–12.6%. The average recoveries were between 96.4 and 104.6%. The limits of quantitation were 2.0 × 10⁻³ and 2.5 × 10⁻³ μg mL⁻¹ for triptolide and tripdiolide.     

Removal of U(VI) from aqueous solutions by using MWCNTs and chitosan modified MWCNTs

In this paper, the multiwalled carbon nanotubes (MWCNTs) were modified with chitosan (CS) by using low temperature plasma grafting technique (denoted as MWCNT-CS). The prepared MWCNTs and MWCNT-CS were characterized by SEM, TEM, FTIR and Raman spectroscopy in detail and the results suggested that CS molecules were successfully grafted on the surfaces of MWCNTs. The materials were applied as adsorbents in the removal of U(VI) ions from large volumes of aqueous solutions as a function of environmental conditions. The removal of U(VI) from aqueous solution to MWCNTs and MWCNT-CS increased with increasing pH values at pH < 7, and then decreased with increasing pH values at pH > 7. The sorption of U(VI) on MWCNTs and MWCNT-CS was strongly dependent on pH and independent of ionic strength. The sorption of U(VI) on MWCNTs and MWCNT-CS was dominated by inner-sphere surface complexation rather than by ion exchange or outer-sphere surface complexation. The surface grafted chitosan molecules can enhances U(VI) sorption on MWCNTs obviously, which was also evidenced from the XPS spectroscopy analysis. The results of high sorption capacity of U(VI) on MWCNT-CS suggest that the MWCNT-CS nanomaterial is a suitable candidate in the preconcentration of U(VI) ions from large volumes of aqueous solutions.     

Inhibitor Development against p7 Channel in Hepatitis C Virus

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Several classes of compounds, such as amantadine and rimantadine have been testified for p7 inhibition. However, the efficacies of these compounds are not high. Here, we screened some novel p7 inhibitors with amantadine scaffold for the inhibitor development. The dissociation constant (Kd) of 42 ARD-series compounds were determined by nuclear magnetic resonance (NMR) titrations. The efficacies of the two best inhibitors, ARD87 and ARD112, were further confirmed using viral production assay. The binding mode analysis and binding stability for the strongest inhibitor were deciphered by molecular dynamics (MD) simulation. These ARD-series compounds together with 49 previously published compounds were further analyzed by molecular docking. Key pharmacophores were identified among the structure-similar compounds. Our studies suggest that different functional groups are highly correlated with the efficacy for inhibiting p7 of HCV, in which hydrophobic interactions are the dominant forces for the inhibition potency. Our findings provide guiding principles for designing higher affinity inhibitors of p7 as potential anti-HCV drug candidates.     

Effect of Protective Measures on Eye Exposure to Solar Ultraviolet Radiation

In this study, ocular biologically effective exposure to solar ultraviolet radiation (UVBE) is investigated with six kinds of sun protective measures (spectacle lenses, sunglasses, cap, bonnet, straw hat and under parasol). Ocular UV exposure measurements were performed on manikins during the summer period in Shenyang city (41.64° N, 123.50° E, 66 m a.s.l.), China. The measurements include the ocular UV exposure of an unprotected eye and the ambient UV as a control concurrently. Based on the relative spectral weighting factors of the International Commission on Non‐Ionizing Radiation Protection (ICNIRP), the ocular biologically effective UV is calculated and compared with the 8‐h exposure limits of ICNIRP (30 J m^?2). The UV index (UVI) of the measurement days is 0–8, and the 8‐h (8:00–16:00 China Standard Time, CST) cumulated UVBE of the unprotected eye is 452.0 J m^?2. The 8‐h cumulated UVBE of the eye with spectacle lenses, sunglasses, cap, bonnet, straw hat and under parasol are 364.2, 69.1, 51.4, 49.0, 56.8 and 110.2 J m^?2, respectively. Importantly, it should be noted that the eye could be exposed to risk despite protective measures. The 8‐h cumulated UVBE of the eye with protection is ca 1.6–15.1 times the exposure limit, respectively. As indicated in the present study, during summer months, high exposure to the sun for more than 30 min without eye protection and more than 1 h with eye protection is not advisable. The protection measures could effectively reduce the UVBE reaching the eye, yet there is still a high degree of risk when compared with the ICNIRP 8‐h exposure limits.     

2D warp-and-woof interwoven networks constructed by helical chains with different chirality

Two unprecedented 2D entangled layers of warp-and-woof threads interwoven by left- and right-handed helical chains, {[Mn(salen)Au(CN)2]4(H2O)}n (salen = N,N'-ethylenebis(salicylideneaminato)) and {Mn(acacen)Ag(CN)2}n (acacen = N,N'-ethylenebis(acetylacetonylideneiminate)) 2, have been synthesized and characterized.     

Ca、Ba掺杂Sm0.5Sr0.5CoO3作为中低温固体氧化物燃料电池阴极的结构与性能

通过X射线衍射(XRD)、热重、热膨胀、电导率以及电化学交流阻抗等测试技术研究了SmSr1-xAexCo2O6(x=0, 0.2, 0.4, 0.6, 0.8, 1; Ae=Ca, Ba)作为中低温固体氧化物燃料电池(IT-SOFC)阴极的结构与性能. 研究表明, 固相法合成的SmSr0.8Ae0.2Co2O6(Ae=Ca, Sr, Ba; 简写为SSAC)随着Ca、Ba掺杂量的增大晶体结构发生变化. 其中, 空间群为Pnma晶体结构的电极SSAC中, 晶胞参数随着Sr、Ca、Ba的顺序增大; SSAC晶体中的氧空位浓度随着Ca、Sr、Ba的顺序增大, SSAC热膨胀系数与Ae元素关系不大, 氧催化性能随着Ca、Sr、Ba的顺序降低. 由于载流子浓度降低, 使得Ba 掺杂Sm0.5Sr0.5CoO3(SSC)后电极的电导率降低. 由于导电活化能增大, 使得Ca掺杂SSC后电极的电导率也降低.     

Positive Charges in the Brace Region Facilitate the Membrane Disruption of MLKL-NTR in Necroptosis

Necroptosis is a type of programmed cell death executed through the plasma membrane disruption by mixed lineage kinase domain-like protein (MLKL). Previous studies have revealed that an N-terminal four-helix bundle domain (NBD) of MLKL is the executioner domain for the membrane permeabilization, which is auto-inhibited by the first brace helix (H6). After necroptosis initiation, this inhibitory brace helix detaches and the NBD can integrate into the membrane, and hence leads to necroptotic cell death. However, how the NBD is released and induces membrane rupture is poorly understood. Here, we reconstituted MLKL_2–154 into membrane mimetic bicelles and observed the structure disruption and membrane release of the first brace helix that is regulated by negatively charged phospholipids in a dose-dependent manner. Using molecular dynamics simulation we found that the brace region in an isolated, auto-inhibited MLKL_2–154 becomes intrinsically disordered in solution after 7 ns dynamic motion. Further investigations demonstrated that a cluster of arginines in the C-terminus of MLKL_2–154 is important for the molecular conformational switch. Functional mutagenesis showed that mutating these arginines to glutamates hindered the membrane disruption of full-length MLKL and thus inhibited the necroptotic cell death. These findings suggest that the brace helix also plays an active role in MLKL regulation, rather than an auto-inhibitory domain.