特定环状RNA表达与衰老的关系研究*

目的:研究小鼠不同组织器官中环状RNA的表达量在年老与年幼中的差异,揭示环状RNA与衰老的联系。方法:通过对不同组织器官的总RNA的提取,分别逆转录,并扩增circUSP34、circTCF4、circTCF20、circZFP64、circPWWP2A、circLIN54,通过凝胶电泳比较其在年轻小鼠与年老小鼠的组织器官中的表达情况,明确上述环状RNA与衰老的联系。结果:环状RNA在不同年龄小鼠的组织器官中存在广泛性的差异性表达,不同组织不同环状RNA有着不同的表达量的改变,其与衰老存在联系。在卵巢中除circTCF4,其余五种环状RNA表达量均与年龄负相关;在肾脏中,除circTCF4与circPWWP2A,其余与年龄呈负相关;在乳腺中只有circUSP3与衰老呈负相关;而在肠道与生长相关的只有上述后三种环状RNA,均呈正相关。其他样本与组织的发育阶段有不同的相关性,具体在结果体现。结论:环状RNA的表达量在组织中与年龄的增大有着显著相关性,环状RNA可能广泛地参与了不同的衰老通路,起到不同的生物学作用,其在衰老的产生中扮演重要角色。     

两种内镜手术对消化道神经内分泌肿瘤的切除效果及安全性评价

目的:探讨内镜下两种手术方法对消化道神经内分泌肿瘤的切除效果和安全性。方法:选取64例消化道神经内分泌肿瘤患者,随机分为A组和B组,每组各32例。A组接受内镜下黏膜切除术,B组接受内镜下黏膜剥离术。分析和比较两组所切除组织的病理学检查结果、手术时间、切除肿瘤的直径和厚度、治疗费用、住院时间、肿瘤完全切除率、垂直切缘阴性率以及并发症的发生率。结果:A组的手术时间为(8.95±1.63) min,治疗费用为(2127.70±468.31)元,均显著少于B组(P0.05);两组患者切除肿瘤直径和厚度、住院时间、垂直切缘阴性率对比差异均没有统计学意义(P0.05);B组的肿瘤完全切除率为93.75%,显著高于A组(P0.05);A组并发症发生率为3.13%,显著低于B组(P0.05)。结论:两种内镜下手术方式均可有效清除消化道神经内分泌肿瘤病灶。内镜下黏膜切除术的手术时间、费用及并发症的发生率更少低,而内镜下黏膜剥离术能够更彻底地清除肿瘤组织。     

Novel hepacivirus in Asian house shrew,China

<正>Dear Editor,Hepatitis C virus (HCV) is a leading global cause of various liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The genome of HCV is monopartite, single-stranded, positive RNA, about 10 kb in size.HCV is the prototype species of the Hepacivirus genus,which contains 14 species according to the update from the International Committee on Taxonomy of Viruses (Smith et al., 2016). Prior to 2005, humans were thought to be the only     

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose‐dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3‐methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX‐527 suppressed melatonin‐induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1‐autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1‐autophagy pathway regulation, which may help us better understand the association between melatonin and IDD.     

Inter‐α‐inhibitor deficiency in the mouse is associated with alterations in anxiety‐like behavior,exploration and social approach

In recent years, several genome‐wide association studies have identified candidate regions for genetic susceptibility in major mood disorders. Most notable are regions in a locus in chromosome 3p21, encompassing the genes NEK4‐ITIH1‐ITIH3‐ITIH4. Three of these genes represent heavy chains of the composite protein inter‐α‐inhibitor (IαI). In order to further establish associations of these genes with mood disorders, we evaluated behavioral phenotypes in mice deficient in either Ambp/bikunin, which is necessary for functional ITIH1 and ITIH3 complexes, or in Itih4, the gene encoding the heavy chain Itih4. We found that loss of Itih4 had no effect on the behaviors tested, but loss of Ambp/bikunin led to increased anxiety‐like behavior in the light/dark and open field tests and reduced exploratory activity in the elevated plus maze, light/dark preference and open field tests. Ambp/bikunin knockout mice also exhibited a sex‐dependent exaggeration of acoustic startle responses, alterations in social approach during a three‐chamber choice test, and an elevated fear conditioning response. These results provide experimental support for the role of ITIH1/ITIH3 in the development of mood disorders.     

Synthesis and Antitumor Evaluation in Vitro of NO‐Donating Ursolic Acid‐Benzylidene Derivatives

Antitumor activity of triterpenoid and its derivatives has attracted great attention recently. Our previous efforts led to the discovery of a series of NO‐donor betulin derivatives with potent antitumor activity. Herein, we prepared eight compounds derived from ursolic acid (UA). All the compounds were evaluated for their in vitro cytotoxicity against four human cancer cell lines (HepG‐2, MCF‐7, HT‐29 and A549). Among the compounds tested, compound 4a was found to be most active against HT‐29 (IC₅₀=4.28 μm ). Further biological assays demonstrated that compound 4a could induce cell cycle arrest at G1 phase and apoptosis in a dose‐dependent manner. In addition, compound 4a was found to upregulate pro‐apoptotic Bax, p53 and downregulate anti‐apoptotic Bcl‐2. All these results suggested that compound 4a is a potential candidate drug for the therapy of colon cancer.     

Determination of oxytetracycline hydrochloride in milk and egg white samples using Ru(bipy)32+–Ce(SO4)2 chemiluminescence

A novel, rapid and sensitive chemiluminescence (CL) method for the determination of oxytetracycline hydrochloride (OTCH) is described in this paper. The presented method was based on the fact that OTCH could immensely enhance the CL of the reaction of cerium sulfate and tris(2,2‐bipyridyl) ruthenium (II) in acidic medium. Under optimal experimental conditions, CL intensity was favorably linear for OTCH in the range 5.0 × 10^?7 to 5.0 × 10^?5 g/ml, with a detection limit of 1.5 × 10^?7 g/ml (S/N = 3). The relative standard detection was 4.76% for 5.0 × 10^?6 g/ml (n = 11). This method was successfully applied to the analysis of OTCH in milk and egg white samples. According to the results of the kinetic curves for OTCH in the Ru(bipy)₃²⁺–Ce(SO₄)₂ CL system, together with CL and ultraviolet (UV)–visible spectra, the possible mechanism of the CL reaction is discussed briefly.     

Chemical synthesis,microbial transformation and biological evaluation of tetrahydroprotoberberines as dopamine D1/D2 receptor ligands

Dopamine D1/D2 receptors are important targets for drug discovery in the treatment of central nervous system diseases. To discover new and potential D1/D2 ligands, 17 derivatives of tetrahydroprotoberberine (THPB) with various substituents were prepared by chemical synthesis or microbial transformation using Streptomyces griseus ATCC 13273. Their functional activities on D1 and D2 receptors were determined by cAMP assay and calcium flux assay. Seven compounds showed high activity on D1/D2 receptor with low IC₅₀ values less than 1?µM. Especially, top compound 5 showed strong antagonistic activity on both D1 and D2 receptor with an IC₅₀ of 0.391 and 0.0757?µM, respectively. Five compounds displayed selective antagonistic activity on D1 and D2 receptor. The SAR studies revealed that (1) the hydroxyl group at C-9 position plays an important role in keeping a good activity and small or fewer substituents on ring D of THPBs may also stimulate their effects, (2) the absence of substituents at C-9 position tends to be more selective for D2 receptor, and (3) hydroxyl substitution at C-2 position and the substitution at C-9 position may facilitate the conversion of D1 receptor from antagonist to agonist. Molecular docking simulations found that Asp 103/Asp 114, Ser 107/Cys 118, and Trp 285/ Trp 386 of D1/ D2 receptors are the key residues, which have strong interactions with the active D1/D2 compounds and may influence their functional profiles.     

无菌APPswe/PS1ΔE9双转基因小鼠模型建立及脑内斑块变化初步观察

目的 使用剖宫产净化方法建立无菌APPswe/PS1ΔE9(PAP)双转基因小鼠模型并对动物脑内斑块沉积情况进行初步观察,为研究肠道菌群与阿尔茨海默症关系提供新的动物模型。方法 选择阳性PAP雄性杂合子鼠与经产的C57野生型雌鼠1∶2进行交配。怀孕母鼠在超净工作台内行剖宫产手术,用无菌ICR小鼠代乳。术后每个月进行无菌状态检测;PCR方法检测剖宫产所得PAP仔鼠的基因型;免疫组化方法定量检测9月龄PAP小鼠脑内斑块变化情况。结果 实施剖宫产手术12例,获仔鼠66只,剖宫产存活率及离乳存活率分别为95.45%(63/66)和95.24%(60/63),净化后按国标检测无菌状态均为合格。免疫组化结果显示9月龄无菌PAP小鼠海马内斑块较同月龄SPF级动物减少。结论 通过剖宫产净化技术去除了PAP小鼠携带的菌群,9月龄无菌PAP小鼠脑内斑块减少。     

石灰岩石器使用功效的模拟实验——以重庆巫山玉米洞遗址为例

本文以巫山玉米洞遗址为例,对石灰岩石器进行复制与使用功效的模拟实验,结果表明有些石灰岩在石器打制层面表现出较好的适用性,石灰岩石器在常规的砍砸、切割、挖掘等行为活动中表现出良好的功能实用性和效率。通过实验标本与遗址出土石器的对比分析,我们认为该遗址应存在优选天然毛坯直接使用而形成的“使用石器”,类型主要集中在砍砸器和手镐等重型工具,但二次加工的石器比“使用石器”更为有效耐用;有尖类石器在作用于硬性对象或结构不稳定、受力不均时容易产生残损,与出土有尖类石器较高的残损率相吻合;把手修理在石器使用过程中显得非常必要,为遗址出土石器普遍存在把手修理现象提供了合理解释。