乳酰化修饰在疾病中的作用及机制研究进展

乳酸是细胞呼吸的产物。葡萄糖进入细胞后,在己糖激酶等的催化作用下通过糖酵解代谢成丙酮酸。当细胞氧供充足时,丙酮酸通过线粒体基质中的丙酮酸脱氢酶转化为乙酰辅酶A参与三羧酸循环,为细胞提供必需的能量。当细胞缺氧时,丙酮酸由胞质中的乳酸脱氢酶催化生成乳酸。乳酸不仅为线粒体呼吸提供能量源,还通过自分泌、旁分泌和内分泌等形式在炎症反应、创伤修复、记忆形成和神经保护以及肿瘤生长和转移等病理生理过程中发挥重要作用,影响疾病发展和预后。表观遗传修饰是通过修饰酶共价添加或水解组蛋白和DNA结构中的功能基团以调节基因复制、转录和翻译等过程,影响细胞生物学效应。组蛋白是真核生物染色体的基本结构蛋白,其翻译后修饰诸如甲基化、乙酰化等影响其与DNA双链的亲和性,改变染色质结构,广泛参与基因的表达调控。最新研究发现组蛋白上可以发生乳酰化修饰,即通过对组蛋白上的赖氨酸残基添加乳酸基团,使其作为一种全新的表观遗传修饰发挥作用。随着研究的深入,乳酰化修饰也被证明广泛发生在非组蛋白上。乳酰化修饰的发现扩大了对乳酸参与疾病病理机制的认识。该文主要综述了乳酰化修饰在肿瘤、炎性疾病和神经系统疾病中的作用和机制,以期为相关疾病的研究与诊疗提供新思路。

蛋白质乳酰化翻译后修饰的功能研究进展

蛋白质翻译后修饰通过调控基因表达、改变信号通路活化、影响细胞内代谢通路等对机体多种生理和病理过程产生重要影响。乳酰化修饰是近年来新发现的一种由乳酸促进产生的蛋白质翻译后修饰,其由乙酰转移酶p300介导,且与乳酸的含量密切相关。目前的研究发现组蛋白乳酰化修饰的改变与肿瘤及各种其他疾病(如阿尔茨海默病、肺纤维化)的发生发展密切相关。其他蛋白质乳酰化则与真菌毒力和脓毒症进展有关。因此,关注蛋白质乳酰化在疾病发生发展过程中的作用,可能为疾病的治疗提供新思路。

非包衣乙酰化β-乳球蛋白肠溶片的制备及处方优化

目的研究乙酰化β-乳球蛋白作为新型肠溶辅料的特性,制备乙酰化β-乳球蛋白为肠溶辅料的阿司匹林非包衣肠溶片,并对其进行处方优化。方法使用乙酸酐对β-乳球蛋白进行乙酰化改性,考察改性后的β-乳球蛋白在不同p H环境下的溶解度及稳定性。以阿司匹林为模型药物,乙酰化β-乳球蛋白为肠溶填充辅料制备非包衣肠溶片,并利用Box-Behnken法对非包衣肠溶片的处方和工艺进行优化。结果乙酰化改性使β-乳球蛋白等电点向低p H端偏移,实现了乙酰化β-乳球蛋白在p H<5.2环境下溶解度的降低和稳定性的提高,因此显现出了一定的肠溶释药性能。对制备的阿司匹林非包衣肠溶片进行处方及工艺优化后,实现了药物在酸性条件下2 h释放量低于2%且在中性环境下45 min释放量达到97%的肠溶释放效果。结论经乙酰化改性的β-乳球蛋白可作为一种新型的肠溶辅料应用于非包衣肠溶片的制备,所制备的非包衣肠溶片具有良好的肠溶释药效果。

Synthesis of allyl 4-O-{3-deoxy-3-[4-benzylaminocarbonyl-1H-(1,2,3)-triazol-l-yl]-β-D-galactopyranosyl}-2-deoxy-2-acetamido-β-D-glucopyranoside as a potential inhibitor of galectin-3

Allyl 4-O-{3-deoxy-3-[4-benzylaminocarbonyl-1H-（1,2,3）-triazol-1-yl]-β-D-galactopyranosyl}-2-deoxy-2-acetamido- β-D-glucopyranoside, a potential inhibitor of galectin-3, was designed and synthesized using lactose as stating material. The modifications of lactose included in introducing of N-acetamino group at the C-2 position through an azidoiodoglycosylation meanwhile constructing the [3-aminolactoside stereoselectively and replacing 3＇-OH with substituent 1,2,3-triazolyl group to enhance the affinity toward galeetin-3.

Response of Rice Varieties to Bound Residues of Metsulfuron-Methyl in a Paddy Soil

Metsulfuron-methyl is one of the widely used sulfonylurea herbicides. However, approximately half of the applied metsulfuron-methyl may remain as bound residues in soil. To characterize the response of rice plants to residual metsulfuron-methyl in soil, the activities of acetolactate synthase （ALS）, superoxide dismutase （SOD）, peroxidase （POD）, and catalase （CAT） were investigated in two rice varieties that differed in susceptibility to the herbicide. Changes in the activity of these enzymes in leaves and roots of Xiushui 63, a sensitive rice variety, were greater than those in a resistant variety Zhenong 952. Irrespective of variety, changes in the enzyme activity were greater in the roots than in the leaves. The activities of ALS and CAT decreased, while the SOD activity increased with the increase in the amounts of bound residues of metsulfuron-methyl （BRM） in soil. The POD activity increased at the BRM level of 0.025 mg kg^-1, but decreased at the BRM level of 0.05 mg kg^-1. The results showed that the bound residues of sulfonylurea herbicides may affect metabolism of rice plants.

Multiple Resistance to Acetyl Coenzyme A Carboxylase and Acetolactate Synthase Inhibiting Herbicides in Tunisian Ryegrass Populations （Lolium rigidum）

The good understanding of the mechanisms of resistance to herbicides in weeds is a necessity to implement sustainable weed management strategies. Here, a study was conducted to characterize the molecular bases of resistance to acetyl coenzyme A carboxylase （ACCase） and acetolactate synthase （ALS） inhibiting herbicides in Lolium rigidum populations from Tunisia. Nine Lolium rigidum （ryegrass） populations collected in wheat fields from Northern Tunisia were investigated for their resistance to two ACCase-inhibiting herbicides and an ALS-inhibiting herbicide. All populations were tested in the greenhouse in pots using the commercial dose to determine resistance status. Survival plants were also tested for the presence of two ACCase （L 1781 and N2041） and two ALS （P197 and W574） mutant resistant alleles using molecular markers. Resistance to ACCase-inhibiting herbicides was found in all tested populations. Comparison of the results from herbicide sensitivity bioassays with genotyping indicated that more than 80% of the plants resistant to ACC-inhibiting herbicides would be resistant via increased herbicide metabolism. However, ALS-inhibiting herbicides are still more or less controlling ACCase resistant populations, so indicating that the selection process of resistance is ongoing. Target-site resistance appears to be the major mechanism for these early cases of ALS inhibitor resistance. This study reported the first case of resistance to ALS-inhibiting herbicides in ryegrass in Tunisia, and investigated the molecular bases of this resistance. It establishes the clear importance of non target-site resistance to ACCase- and/or ALS-inhibiting herbicides.

The side effects of docetaxel with cyclophosphamide as postoperative adjuvant chemotherapy for elderly breast cancer patients

Objective: The aim of this study was to investigate the side effects of docetaxel with cyclophosphamide as postoperative adjuvant chemotherapy for elderly breast cancer patients. Methods: Thirty-six operable elderly breast cancer patients at intermediate risk based on the St Gallen risk classification underwent modified radical mastectomy and then were given four cycles of TC regimen (docetaxel 75 mg/m2 i.v. on day 1; cyclophosphamide 600 mg/m2 i.v. on day 1; every 21 days ). Primary prophylaxis granulocyte colony stimulating factor (G-CSF) 200μg i.h. was administered on day 4-6. Results: The main side effect was neutropenia. Grade 3 neutropenia developed in 36.1% and G4 in 19.4%, respectively. Most of the other side effects were G1-2. Dose reduction occurred in 11.1% patients. The completion rate of chemotherapy was 100%. Conclu-sion: Docetaxel with cyclophosphamide as postoperative adjuvant chemotherapy regimen with G-CSF primary prophylaxis is tolerable for elderly patients in general good condition.

The Effect and Benefit of Rice Chilo suppressalis Walker Chemical Control Test of Chlorantraniliprole etc.

In this paper, the first generation and second generation of Chilo suppressalis Walker were conducted as the test objects to investigate control of a new pesticide(chlorantraniliprole) with preparation of chlorantraniliprole 20% SC,abamectin 1.8% EC and chlorpyrifos 40% EC to Chilo suppressalis Walker. The results showed that chlorantraniliprole 20% SC, abamectin 1.8% EC and chlorpyrifos40% EC had effective control to Chilo suppressalis Walker for its excellent control efficacy and long persistence period. Seedling protection efficacies were between84.2%-100%, 90.1% and 92.1%, and insecticidal efficacies were between 84.6%-100%,90.7% and 93.8% 36 days after application of chlorantraniliprole 20% SC in treatments with abamectin 1.8% EC and chlorpyrifos 40% EC for first generation Chilo suppressalis Walker control. The dead panicles were between 0.2%-1.4%, 0.8%and 0.7%, pest plant rate control in 0.4%-2.2%, 1.1% and 0.9%, and the rates of damaged rice plants were between 82.4%-97.6%, 90.2%-91.2% and 91.4%-92.8%,30 days after application of chlorantraniliprole 20% SC, abamectin 1.8% EC and chlorpyrifos 40% EC for the second generation Chilo suppressalis Walker control. It can effectively protect seedlings, protect spike, increase grain number and grain weight, which promoting the increase production income effect. The real estate increased by 9.7%-12.3%, 10.9% and 11.2% than water treatment(CK) with a very significant level, while the incomes were higher than 1 719.19-1 998.22, 1 956.52 and 2 057.83 yuan.

Catalytic transformations of cellulose and its derived carbohydrates into 5-hydroxymethylfurfural, levulinic acid, and lactic acid

The catalytic transformation of cellulose into key building-block or platform chemicals such as 5-hydoxymethylfurfural(HMF),levulinic acid,and lactic acid under mild conditions,has attracted much attention in recent years,as these conversions can be operated without consumption of hydrogen or oxygen and thus are more economical compared to the hydrogenolysis or oxidation of cellulose.This review article highlights recent advances in the development of novel catalysts or catalytic processes for the conversion of cellulose and its derived carbohydrates into HMF,levulinic acid,and lactic acid or their esters under inert atmosphere.We also analyze efficient catalytic systems for HMF production,in particular Lewis acids combined with ionic liquid or biphasic systems.For the formations of levulinic and lactic acids or their esters,we focus on the reactions in aqueous and alcohol media catalyzed by multifunctional catalysts that combine the functions of hydrolysis,isomerization,and dehydration-rehydration or retro-aldol reactions.The reaction mechanism for each process will also be discussed to gain insights into the activation of C–O and C–C bonds in the absence of hydrogen or oxygen.