The Evidence for Effective Inhibition of INa Produced by Mirogabalin ((1R,5S,6S)-6-(aminomethyl)-3-ethyl-bicyclo [3.2.0] hept-3-ene-6-acetic acid), a Known Blocker of CaV Channels

Mirogabalin (MGB, Tarlige^®), an inhibitor of the α₂δ-1 subunit of voltage-gated Ca²⁺ (Ca_V) channels, is used as a way to alleviate peripheral neuropathic pain and diabetic neuropathy. However, to what extent MGB modifies the magnitude, gating, and/or hysteresis of various types of plasmalemmal ionic currents remains largely unexplored. In pituitary tumor (GH₃) cells, we found that MGB was effective at suppressing the peak (transient, I_Na(T)) and sustained (late, I_Na(L)) components of the voltage-gated Na⁺ current (I_Na) in a concentration-dependent manner, with an effective IC₅₀ of 19.5 and 7.3 μM, respectively, while the K_D value calculated on the basis of minimum reaction scheme was 8.2 μM. The recovery of I_Na(T) inactivation slowed in the presence of MGB, although the overall current–voltage relation of I_Na(T) was unaltered; however, there was a leftward shift in the inactivation curve of the current. The magnitude of the window (I_Na(W)) or resurgent I_Na (I_Na(R)) evoked by the respective ascending or descending ramp pulse (V_ramp) was reduced during cell exposure to MGB. MGB-induced attenuation in I_Na(W) or I_Na(R) was reversed by the further addition of tefluthrin, a pyrethroid insecticide known to stimulate I_Na. MGB also effectively lessened the strength of voltage-dependent hysteresis of persistent I_Na in response to the isosceles triangular V_ramp. The cumulative inhibition of I_Na(T), evoked by pulse train stimulation, was enhanced in its presence. Taken together, in addition to the inhibition of Ca_V channels, the Na_V channel attenuation produced by MGB might have an impact in its analgesic effects occurring in vivo.     

Dynamic Changes in Reactive Oxygen Species in the Shoot Apex Contribute to Stem Cell Death in Arabidopsis thaliana

In monocarpic plants, stem cells are fated to die. However, the potential mechanism of stem cell death has remained elusive. Here, we reveal that the levels of two forms of reactive oxygen species (ROS), superoxide anion free radical (O2·−) and hydrogen peroxide (H₂O₂), show dynamic changes in the shoot apex during the plant life cycle of Arabidopsis thaliana. We found that the level of O2·− decreased and disappeared at four weeks after bolting (WAB), while H₂O₂ appeared at 3 WAB and showed a burst at 5 WAB. The timing of dynamic changes in O2·− and H₂O₂ was delayed for approximately three weeks in clv3-2, which has a longer lifespan. Moreover, exogenous application of H₂O₂ inhibited the expression of the stem cell determinant WUSCHEL (WUS) and promoted the expression of the developmentally programmed cell death (dPCD) marker gene ORESARA 1 (ORE1). These results indicate that H₂O₂ triggers an important signal inducing dPCD in stem cells. Given that O2·− plays roles in maintaining WUS expression and stem cell activity, we speculate that the dynamic shift from O2·− to H₂O₂ in the shoot apex results in stem cell death. Our findings provide novel insights for understanding ROS-mediated regulation during plant stem cell death.     

2-(2,5-二氨基苯)乙醇的合成

在二氯乙烷介质中,将3-氟苯乙酸于70℃下硝化4 h得到5-氟-2-硝基苯乙酸(质量分数为67.8%)。用硼烷还原5-氟-2-硝基苯乙酸后,接着用氨水在高压釜中加热到100℃氨解,得到2-(5-氨基-2-硝基苯)乙醇(84.4%)。最后,10%Pd/C作催化剂,在无水异丙醇介质中,0.6～0.7 MPa下,于70～80℃催化氢化12 h,得到目标分子2-(2,5-二氨基苯)乙醇(64%)。与文献工艺相比,目标分子总收率提高11%。用H–NMR和MS确定了目标分子2-(2,5-二氨基苯)乙醇的化学结构。     

改性Mo/HZSM-5催化剂甲烷无氧芳构化反应条件研究

采用Mo担载的质量分数为6%、经过先碱后酸预处理的Mo/HZSM-5作为催化剂,在不同反应温度和反应空速下,比较了甲烷的转化率、苯的生成速率和积炭的收率.结果表明,当反应温度为700℃,反应空速为1 400 mL/(g·h)时,甲烷无氧芳构化性能最佳.     

2-(5-Br-2-吡啶偶氮)-5-二甲氨基苯酚吸光光度法测定微量锌的研究

研究了显色剂2-(5-Br-2-吡啶偶氮)-5-二甲氨基苯酚(5-Br-DMPAP)吸光光度法测定Zn(Ⅱ)的新方法。在pH值为9.0时,Zn(Ⅱ)与5-Br-DMPAP和非离子表面活性剂乙二醇辛基苯醚(OP)发生高灵敏的显色反应,生成稳定的紫红色配合物。该配合物在556nm处有一最大吸收波长,Zn(Ⅱ)含量在(0～25)μg/25mL范围内符合比耳定律,表观摩尔吸光系数为ε=7.74×104L.mol-1.cm-1,检出限为0.2μg/25mL。方法用于奶粉中微量锌的测定,结果满意。     

合成C5石油树脂催化剂的研究

研制了一种酸性离子溶液,它是一种新型的催化剂溶液,可广泛应用于均相催化.使用这种催化剂离子溶液催化合成C5石油树脂,研究了催化剂用量、温度和添加方式对聚合反应的影响.     

Effect of Betaine and Arginine on Interaction of αB-Crystallin with Glycogen Phosphorylase b

Protein–protein interactions (PPIs) play an important role in many biological processes in a living cell. Among them chaperone–client interactions are the most important. In this work PPIs of αB-crystallin and glycogen phosphorylase b (Phb) in the presence of betaine (Bet) and arginine (Arg) at 48 °C and ionic strength of 0.15 M were studied using methods of dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation. It was shown that Bet enhanced, while Arg reduced both the stability of αB-crystallin and its adsorption capacity (AC₀) to the target protein at the stage of aggregate growth. Thus, the anti-aggregation activity of αB-crystallin increased in the presence of Bet and decreased under the influence of Arg, which resulted in inhibition or acceleration of Phb aggregation, respectively. Our data show that chemical chaperones can influence the tertiary and quaternary structure of both the target protein and the protein chaperone. The presence of the substrate protein also affects the quaternary structure of αB-crystallin, causing its disassembly. This is inextricably linked to the anti-aggregation activity of αB-crystallin, which in turn affects its PPI with the target protein. Thus, our studies contribute to understanding the mechanism of interaction between chaperones and proteins.     

Expression of Irisin/FNDC5 in Breast Cancer

Irisin is a myokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. FNDC5 and irisin levels have been poorly studied in the tumor tissues of breast cancer (BC). The aim of this study was to determine the levels of irisin expression in BC tissues and compare them to clinicopathological factors and Ki-67 and PGC-1α expression levels. Tissue microarrays (TMAs) with 541 BC tissues and 61 samples of non-malignant breast disease (NMBD; control) were used to perform immunohistochemical reactions. FNDC5 gene expression was measured in 40 BC tissue samples, 40 samples from the cancer margin, and 16 NMBD samples. RT-PCR was performed for the detection of FNDC5 gene expression. Higher irisin expression was found in BC patients compared to normal breast tissue. FNDC5/irisin expression was higher in patients without lymph node metastases. Longer overall survival was observed in patients with higher irisin expression levels. FNDC5/irisin expression was increased in BC tissues and its high level was a good prognostic factor for survival in BC patients.