Functional analysis of the novel mitochondrial tRNA^(Trp)and tRNA^(Ser(AGY))variants associated with type 2 diabetes mellitus

BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

A novel molybdenite depressant for efficient selective flotation separation of chalcopyrite and molybdenite

A novel small molecule depressant(M-DEP)was used to separate chalcopyrite and molybdenite via flotation.The results showed that M-DEP had an excellent selective depression on molybdenite,while had little effect on the flotation of chalcopyrite.The adsorption capacity of M-DEP on the surface of molybdenite was greater than that on chalcopyrite surface.The adsorption of M-DEP reduced the floatability of molybdenite and had less effect on the floatability of chalcopyrite,which was due to its different adsorption modes on the surface of the two minerals.Furthermore,the interaction between chalcopyrite and M-DEP was mainly chemical interaction,and almost all of the adsorbed M-DEP molecules were removed and replaced by sodium butyl xanthate(SBX).By contrast,hydrophobic interaction was the main way in which M-DEP was adsorbed on the molybdenite surface with little chemical interaction,which was less interfered by SBX addition.Therefore,M-DEP had a super selective depression on molybdenite.The study provided a novel depressant and approach for the deep separation of chalcopyrite and molybdenite via flotation.

Exploring the mechanism of a novel cationic surfactant in bastnaesite flotation via the integration of DFT calculations,in-situ AFM and electrochemistry

Effectively separating bastnaesite from calcium-bearing gangue minerals(particularly calcite)presents a formidable challenge,making the development of efficient collectors crucial.To achieve this,we have designed and synthesized a novel,highly efficient,water-soluble cationic collector,N-dodecylisopropanolamine(NDIA),for use in the bastnaesite-calcite flotation process.Density functional theory(DFT)calculations identified the amine nitrogen atom in NDIA as the site most susceptible to electrophilic attack and electron loss.By introducing an OH group into the traditional collector dodecylamine(DDA)structure,NDIA provided additional adsorption sites,enabling synergistic adsorption on the surface of bastnaesite,thereby significantly enhancing both the floatability and selectivity of these minerals.The recovery of bastnaesite was 76.02%,while the calcite was 1.26%.The NDIA markedly affected the zeta potential of bastnaesite,while its impact on calcite was relatively minor.Detailed Fourier-transform infrared spectroscopy(FTIR)and X-ray photoelectron spectroscopy(XPS)results elucidated that the―NH―and―OH groups in NDIA anchored onto the bastnaesite surface through robust electrostatic and hydrogen bonding interactions,thereby enhancing bastnaesite's affinity for NDIA.Furthermore,in situ atomic force microscopy(AFM)provided conclusive evidence of NDIA aggregation on the bastnaesite surface,improving contact angle and hydrophobicity,and significantly boosting the flotation recovery of bastnaesite.

Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide.Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and evolution.Emerging evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well defined.AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies.METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this study.We investigated genetic alterations of FABPs in various cancer types.mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with HCC.We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells.RESULTS We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in cancer.Amplification,in fact,is the most common genetic alteration for FABPs,leading to overexpression of FABPs.FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues.High FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0.22,P=1.6e-5).Furthermore,FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients(r=0.58,P=0;r=0.58,P=0;respectively).FABP5high Huh7 cells also expressed higher protein levels of p53,BIRC5,CDK1,CDK2,and CDK4 than FABP5low HepG2 cells.FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells.CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer,especially in HCC,leading to its significant elevated expression in HCC.Its high expression correlates well with worse patient outcome,enriched cancer hallmarks and oncogenes in HCC.FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells.All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Analyzing the Adaptation of Rebecca from the Novel to the Film in Light of the Black-and-White

Classical Chinese aesthetics is based on Chinese philosophy.The characteristic of classical Chinese aesthetics regards“artistic conception”as one of the basic aesthetic categories.Chinese art speaks highly of the charm of the black-and-white.During the adaptation,there is the same beauty in the black-and-white photography and the“color without color”of Chinese paintings.The“artistic conception”is similar between them from the aesthetic perspective.Therefore,the unique“artistic conception”of the novel should be mastered,if the adapter aims to retain the“soul”of it.In other words,film adaptation not only considers“similarity in form”,but also draws much attention to“similarity in spirit”.The latter is the essence of film adaptation.

Prevention and Nursing of Adverse Reactions of Novel Coronavirus Inactivated Vaccine (Vero Cells)

Objective:To discuss and analyze the causes of adverse reactions caused by the inactivated novel coronavirus vaccine(Vero cells),and to propose methods of prevention and care.Methods:A questionnaire was used to randomly select 229 adults who were vaccinated with the inactivated novel coronavirus vaccine(Vero cells)at Xi’an People’s Hospital(Xi’an Fourth Hospital).The adverse reactions were statistically analyzed.Results:Among the 229 adults vaccinated with the inactivated novel coronavirus vaccine(Vero cells),30 experienced vaccination reactions.The main reaction was local induration at the inoculation site,and dizziness was the primary systemic symptom.Conclusion:To reduce the incidence of adverse reactions to the inactivated novel coronavirus vaccine(Vero cells),it is necessary to effectively evaluate the health status of adults before vaccination,select the correct vaccination site,and strictly implement the rules of 3-inspections,7-checks,and 1-verification.Standardizing the operation process and providing thorough health education after vaccination can effectively reduce the occurrence of adverse reactions.

The Application of Newmark’s Metaphor Theory in Novel Translation--A Case Study of“the Jade King:History of a Chinese Muslim Family”

This paper examines the metaphorical part of“The Jade King:History of a Chinese Muslim Family”,Hoda’s novel,under the guidance of Newmark’s theory of metaphor.Newmark proposes six categories of metaphors,namely Dead Metaphor,ClichéMetaphor,Stock or Standard Metaphor,Adapted Metaphor,Recent Metaphor,Original Metaphor;and seven strategies of metaphor translation,including reproducing the same image in the target language,replacing the image in the source language with a standard target language image,translation of metaphor by simile,translation of metaphor(or simile)by simile plus sense,conversion of metaphor to sense,deletion and same metaphor combined with sense.They can provide a strong theoretical support for analyzing the expressions of metaphors in novels and their translation methods.By deeply analyzing the expressions of metaphor and its translation methods in novels,it not only helps to understand the metaphorical meaning and cultural connotation of the original works,but also helps to explore the cultural differences and challenges faced by English and Chinese bilingualism in the process of metaphor translation,thereby significantly improving the translation level and promoting the development of translation research.

A Novel Insulator and Its Characteristics

Both the ceramic and the composite insulators have their own advantages and disadvantages when compared with each other. It is a reasonable idea to combine their merits together to design a novel insulator. The key measure of the novel insulator suggested in this paper is to add an annular metal sheet coated with high temperature vulcanisation (HTV) silicone rubber (SIR) at the base of the traditional ceramic insulator cap. The HTVSIR covering on the exterior of the metal sheet can lengthen the creepage distance. The metal sheet can uniform the electric stress, reduce its maximum value and modify its direction on one insulator unit and acts as equalizing ring on an insulator string. The factors stated above are the main reasons why the novel insulator has better insulating performance, including lower leakage current and flashover voltage, especially under polluted conditions. Simultaneously, the novel insulator can overcome the disadvantages of the ordinary remedies which have been widely used to improve the performance of ceramic insulators against pollution. The experimental results obtained in the laboratory were in good agreement with the theoretical analysis and demonstrated the novel insulator's effectiveness.

多媒体看图CAI课件的研制及其在NOVELL网上的应用

介绍多媒体看图 CAI课件的特点 ,开发方法 ,制作过程及在 NOVELL 局域网上的应用和教学效果。

对Novel Pedar足底压力分布测量系统应用技术的初步开发

运动员的运动技术动作和足底对地面的作用压力分布有着密切的关系 ,因此如何测试运动员足底作用压力分布并得出准确数据显得非常重要。通过对最新引进的德国 Novel Pedar足底压力分布测量系统进行开发 ,发现其系统软件具有应用技术功能 ,得出落地瞬间足底压力的分布图及最大力、每 cm2 最大压力、每 cm2 平均压力的参数值 ,绘制出步态的压力峰值三维示意图和落地瞬间压力曲线图 。

Novell网络与DCS的连接与通讯

本文针对DCS系统和Novell网络的特点,给出了一种实现DCS和Novell网络连接及数据通讯的方法。文中详细地介绍了该方法的实现原理,最后给出了该方法的一个应用实例。

有限元分析冠状动脉新型刻痕球囊的安全性及有效性

背景:目前临床上使用的冠状动脉介入预扩张球囊主要是传统的高压球囊、乳突球囊等,它们在病变血管中可能会出现滑脱进而擦伤血管的情况。目的:评估新型旋刻球囊在血管扩张中的安全性及有效性。方法:(1)有限元分析:通过采集相关人体组织数据建立血管三维有限元模型,随后建立乳突球囊植入血管三维有限元模型与旋刻球囊植入血管三维有限元模型,分析不同充气压下球囊扩张时的血管应力、血管位移、球囊应力、球囊位移。(2)动物实验:将8只新西兰大耳兔随机分成2组,在髂动脉中分别植入乳突球囊与旋刻球囊进行扩张,每组4只。球囊撤出后取材,苏木精-伊红染色与透射电镜观察血管损伤情况。结果与结论:(1)有限元分析:两种球囊的弹力性质无明显差异,在相同充气压下,乳突球囊组血管应力、血管位移、球囊应力、球囊位移均远远大于旋刻球囊组,并且各指标的均匀性优于旋刻球囊组;随着充气压的增加,乳突球囊组血管应力、血管位移、球囊应力、球囊位移增加幅度远远大于旋刻球囊组。(2)动物实验:苏木精-伊红染色与透射电镜观察显示,旋刻球囊扩张造成的血管损伤只局限在内膜,而乳突球囊扩张造成的血管损伤比较严重,内膜、中膜损伤严重,部分节段可以看到血肿形成,血管周围的炎性细胞较多,局部可见有巨噬细胞堆积。(3)结果表明:相较于乳突球囊扩张,旋刻球囊扩张造成血管闭塞以及夹层的风险较小,但有一定出现球囊弯曲的概率。

LYRIC在人肝癌组织中的表达及其临床意义

目的:检测LYRIC分子在肝癌和癌旁组织中的表达,探讨LYRIC分子与肝癌患者临床病理特征的关系及其对预后判断的指导意义。方法:收集2005年1月至2013年12月沈阳军区总医院和中国医科大学附属盛京医院的87例肝癌患者肝癌及其癌旁组织切除标本,采用Real-time PCR和免疫组织化学染色等方法从基因和蛋白水平检测肝癌患者的癌组织及相应的癌旁组织中LYRIC分子的表达,结合患者病理指标、病理分型和预后随访资料分析LYRIC分子表达的临床意义。结果:在基因水平检测发现,LYRIC基因在56例肝癌组织中表达高于癌旁组织,高表达率为64.7%(56/87);在蛋白水平检测发现,LYRIC蛋白在87例肝癌组织中均表达,且在肝癌组织中的表达显著高于癌旁组织(2.16±0.87 vs 1.63±0.88,P=0.000 1)。在肝癌组织中LYRIC分子的高、低表达可较好地预测肝癌患者的预后情况,LYRIC分子高表达患者预后较差(Log-rank10.236,P=0.001);多因素分析提示,LYRIC高表达(HR=2.19)、转移(HR=2.44)及肿瘤分期(HR=2.01)是影响肝癌总体生存期的独立危险因素,而与肿瘤直径及是否有病毒感染无关。结论:LYRIC分子在肝癌组织中高表达,且其表达水平与肝癌的临床分期、转移能力和临床预后密切相关,是肝癌潜在的预后判断指标。

NOVELL无盘网络使用与改造升级常见问题与分析

本文以实践为基础 ,分析了NOVELL无盘网络系统安装维护及改造升级中常见故障的现象和原因 ,给出了对NetWare系统管理员和用户有参考意义的解决方法。

基于Novell网的高校实验室管理系统设计与实施

文章介绍了基于Novell网的高校实验室管理系统设计与实施。该系统提供了用户统一身份验证,文件发布,策略管理,资产管理,用户日志管理等相关功能。该文提供了相关的实施步骤及功能介绍。

NOVELL网络常见错误的检测与排除

论述用Ｃ语言编程实现的ＮＯＶＥＬＬ网络常见错误数据库的设计，及其常见错误检测与排除系统的主程序编程技术，并提供常见错误信息的利用与故障排除实例．

利伐沙班在犬和猫临床应用的研究进展

血栓栓塞是犬、猫临床上多种疾病的并发症,可累及动脉或静脉,预后较差。目前兽医临床防治血栓栓塞可用的抗血栓药物种类有限,影响临床诊疗水平,引入新药具有实际意义。利伐沙班是一种新型非维生素K拮抗剂类口服抗凝药物,研究证明其能够特异性抑制活性凝血因子X从而抑制血栓形成。近年来人医领域对利伐沙班的相关临床研究逐渐丰富,涉及单用利伐沙班或使用双通路抑制疗法防治不同类型的动、静脉血栓栓塞,可为其应用于兽医临床提供据。犬、猫临床使用利伐沙班的研究正相继开展,论文就犬、猫血栓栓塞疾病发病情况、防治现状,利伐沙班的药理学特性及其在人医、兽医领域的临床试验研究进展进行综述,以期为兽医临床上利伐沙班的进一步研究提供参考。

小鼠3D3／LYRIC基因重组质粒构建及蛋白表达和定位

目的构建小鼠3D3/LYRIC真核表达载体并证实融合蛋白在细胞内的表达及定位。方法提取小鼠乳腺上皮细胞系C127的mRNA,反转录为cDNA。PCR扩增m3D3/LYRIC全长编码基因,亚克隆至pEGFP-C1表达载体中。将构建的重组质粒测序并转染到腺样囊性癌细胞系ACC-2中,提取细胞蛋白进行Western blot检测。利用免疫荧光显微镜观察pEGFP-m3D3/LYRIC在腺样囊性癌ACC-2细胞内的定位。结果 m3D3/LYRIC全长基因序列克隆到真核表达载体pEGFP-C1中,酶切鉴定片段大小为1 740 bp。Western blot检测到融合蛋白GFP-m3D3/LYRIC表达,分子量约为91 kDa。pEGFP-C1-m3D3/LYRIC主要在细胞质内定位,在细胞核内未见表达。结论成功构建了m3D3/LYRIC全长基因真核表达载体,pEGFP-m3D3/LYRIC蛋白主要定位于细胞质内。

Novell平台上的光盘数据库网络检索系统

介绍了以Ｎｏｖｅｌ为平台的光盘数据库网络检索系统，阐述了光盘网络软硬件配置，网络拓扑结构，光盘网络的安装和实施方法，论述了系统特点和主要功能。