Adiponectin receptor 1 and small ubiquitin-like modifier 4 polymorphisms are associated with risk of coronary artery disease without diabetes

Background The genes encoding adiponectin receptor 1 （ADIPOR1） and small ubiquitin-like modifier 4 （SUM04） have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease （CAD） without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms （SNPs） in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 （rs7539542-G, rs7514221-C and rs3737884-G） and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery （OR： 6.77, P = 0.009）, the right coronary artery （OR： 4.81, P = 0.028） or a relatively large number of vessels （P = 0.04）. Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles （OR： 5.82, 95% CI： 1.23-27.7, P= 0.013）. Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.

Modification of Classical SPM for Slightly Rough Surface Scattering with Low Grazing Angle Incidence

Based on the impedance/admittance rough boundaries, the reflection coefficients and the scattering cross section with low grazing angle incidence are obtained for both VV and HH polarizations. The error of the classical perturbation method at grazing angle is overcome for the vertical polarization at a rough Neumann boundary of infinite extent. The derivation of the formulae and the numerical results show that the backscattering cross section depends on the grazing angle to the fourth power for both Neumann and Dirichlet boundary conditions with low grazing angle incidence. Our results can reduce to that of the classical small perturbation method by neglecting the Neumann and Dirichlet boundary conditions.

Small Ubiquitin-Like Modifier Conjugating Enzyme with Active Site Mutation Acts as Dominant Negative Inhibitor of SUMO Conjugation in Arabidopsis

Small ubiquitin-like modifier （SUMO） conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and in vitro a SUMO conjugating enzyme with a Cys to Ser change in the active site, and show that it has a dominant negative effect. In planta expression significantly perturbs normal development, leading to growth retardation, early flowering and gene expression changes. We suggest that the mutant protein can serve as a probe to investigate sumoylation, also in plants for which poor genetic infrastructure precludes analysis via loss-of-function mutants.

Over-expression of small ubiquitin-like modifier proteases 1 predicts chemo-sensitivity and poor survival in non-small cell lung cancer

Background Non-small cell lung cancer （NSCLC） is one of the most common malignant tumors.Despite the advances in therapy over the years,its mortality remains high.The aim of this study was to evaluate the expression of small ubiquitin-like modifier （SUMO） proteases 1 （SENP1） in NSCLC tissues and its role in the regulation of vascular endothelial growth factor （VEGF） expression.We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.Methods A SENP1 small interfering RNA （siRNA） was constructed and transfected into the NSCLC cells.VEGF gene expression was analyzed by real-time polymerase chain reaction （RT-PCR）.Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.Results VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues.Inhibition of SENP1 by siRNA was associated with decreased VEGF expression.SENP1 was over-expressed in 55 of the 100 NSCLC samples （55％） and was associated with a moderate and low histological tumor grade （3.6％,38.2％,and 58.2％ in high,moderate and low differentiated tumors,respectively,P=0.046）,higher T stage （10.9％ in T1,and 89.1％ in T2 and T3 tumor samples,P ＜0.001）and TNM stage （10.9％ in stage Ⅰ,and 89.1％ in stages Ⅱ and Ⅲ tumor samples,P ＜0.001）.The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group （76.4％） than that in the SENP1 low expression group （33.3％,P ＜0.001）.Sixty three patients received postoperative chemotherapy,including 34 with SENP1 over-expression and 29 with SENP1 low expression.Among the 34 patients with SENP1 over-expression,22 （64.7％） patients developed recurrence or metastasis,significantly higher than those in the low expression group 27.6％ （8/29） （P=0.005）.Multivariate Cox regression analysis showed that lymph node metastasis （P=0.015）,TNM stage （P=-0.001）,and SENP1 expression level （P=0.002） were independent prognostic factors for the survival of NSCLC patients.Conclusions SENP1 may be a promising predictor of survival,a predictive factor of chemo-sensitivity for NSCLC patients,and potentially a desirable drug target for lung carcinoma target therapy.

Function,mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy

Ubiquitin(Ub)and ubiquitin-like(Ubl)pathways are critical post-translational modifications that determine whether functional proteins are degraded or activated/inactivated.To date,>600 associated enzymes have been reported that comprise a hierarchical task network(e.g.,E1–E2–E3 cascade enzymatic reaction and deubiquitination)to modulate substrates,including enormous oncoproteins and tumor-suppressive proteins.Several strategies,such as classical biochemical approaches,multiomics,and clinical sample analysis,were combined to elucidate the functional relations between these enzymes and tumors.In this regard,the fundamental advances and follow-on drug discoveries have been crucial in providing vital information concerning contemporary translational efforts to tailor individualized treatment by targeting Ub and Ubl pathways.Correspondingly,emphasizing the current progress of Ub-related pathways as therapeutic targets in cancer is deemed essential.In the present review,we summarize and discuss the functions,clinical significance,and regulatory mechanisms of Ub and Ubl pathways in tumorigenesis as well as the current progress of small-molecular drug discovery.In particular,multiomics analyses were integrated to delineate the complexity of Ub and Ubl modifications for cancer therapy.The present review will provide a focused and up-to-date overview for the researchers to pursue further studies regarding the Ub and Ubl pathways targeted anticancer strategies.

曲面综合法少齿数弧齿锥齿轮加工参数计算仿真与切齿试验

少齿数高减比齿轮传动具有体积小和轻量化的优势。根据综合变位和节锥外啮合原理,设计了一对高减速比弧线等高齿锥齿轮,给出了相关的几何限制条件,推导了大、小轮齿面方程。大轮采用成形法加工,小轮采用单面展成法加工,为弥补大轮齿廓曲率的不足,小轮刀齿采用圆弧刃修形,采用曲面综合法优化求解了小轮加工参数;通过建立ease-off差齿面,对齿面修形梯度、传动误差、接触路径与接触线进行了仿真。切齿和滚检试验,验证了高减比弧齿锥齿轮几何设计、刀盘修形加工方法的可行性。

圆管内氦氙混合气体与超临界二氧化碳换热特性对比分析

小型化、高紧凑反应堆系统是陆上多用途能源供给的研究重点,直接热-动循环下的能量转换对冷却剂工质选型提出极高要求。为了明确氦氙混合气体、超临界二氧化碳的工质适用性,本文采用数值模拟方法,对二者在圆管内的换热特性进行计算,对比了2种冷却剂的物性,分析了不同加热功率、入口速度、入口温度对冷却剂换热系数的影响,拟合提出了2种冷却剂工质圆管内换热的经验模型。研究结果表明:反应堆在加热功率超过100 kW/m~2、入口流速大于10 m/s下,对流换热系数较大;氦氙混合气体入口温度在1 000~1 200 K、超临界二氧化碳在入口温度550~600 K附近时,对流换热系数存在极大值;在高雷诺数区(Re>10~4),2冷却剂的修正关系式与计算值吻合良好。本文计算能够为新型反应堆开发提供数据及模型基础。

提升碱化MXene材料性能的策略综述

拥有片层结构的二维过渡金属氮化物和碳化物(MXene)纳米材料是新发现的一种二维材料,可以通过氢氧化钠处理改变MXene材料表面的官能团和官能团的数量,经碱处理过的MXene材料拥有更优良的电化学、吸附等性能,可应用于能量储存和转换、光电催化、柔性传感器等领域。对提升碱化MXene材料性能的策略进行综述。首先可以通过十八烷基胺、氨基、金属离子等小分子修饰碱化MXene材料,还可以通过碱化MXene与金属材料、金属化合物、非金属材料、高分子材料等复合得到复合材料从而提升其性能。还对碱化MXene的发展提出了建议,认为调控碱化MXene材料的性能并降低碱化MXene材料的生产成本是拓展碱化MXene材料实际应用的主要方向。

白炭黑表面修饰及其在橡胶复合材料中的应用

总结了近年来国内外对白炭黑表面修饰的研究进展,介绍了烷氧基偶联剂、环氧官能团、离子液体、生物小分子、小分子橡胶助剂等对白炭黑表面修饰的方法,以及白炭黑表面修饰对白炭黑/橡胶复合材料在轮胎胎面胶中应用性能的影响。此外,还对比了各种改性方式存在的优势和不足,并对白炭黑表面修饰方法的发展前景进行了展望。

基于ERK1/2翻译后修饰调控及空间性调节的抗癌策略研究进展

ERK1/2是一种介导细胞信号转导的关键蛋白,参与调节细胞的染色质重塑、核解体、增殖、存活、代谢、迁移和分化等生物学过程。其过度激活与癌症的发生进展密切相关,机制表现为上游通路分子或调节因子的基因突变使ERK1/2过度激活及针对上述靶点进行抑制后的ERK1/2再激活。因而ERK1/2为一个有潜在价值的靶点。本文对ERK1/2的翻译后修饰调控及空间性调节的机制研究和相应小分子抑制剂的应用现状进行了讨论,总结并展望了目前靶向调控ERK1/2的抗癌策略及针对潜在靶点展开探索的可能性,为ERK1/2作为抗癌理想靶点的开发性研究提供了新思路。

Chronic sleep deprivation induces alterations in DNA and RNA modifications by liquid chromatography-mass spectrometry analysis

Sleep deprivation(SD)is a widespread issue that disrupts the lives of millions of people.These effects ini-tiate as changes within neurons,specifically at the DNA and RNA level,leading to disruptions in neuronal plasticity and the dysregulation of various cognitive functions,such as learning and memory.Nucleic acid epigenetic modifications that could regulate gene expression have been reported to play crucial roles in this process.However,there is a lack of comprehensive research on the correlation of SD with nucleic acid epigenetic modifications.In the current study,we aimed to systematically investigate the landscape of modifications in DNA as well as in small RNA molecules across multiple tissues,including the heart,liver,kidney,lung,hippocampus,and spleen,in response to chronic sleep deprivation(CSD).Using liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis,we characterized the dynamic changes in DNA and RNA modification profiles in different tissues of mice under CSD stress.Specifically,we ob-served a significant decrease in the level of 5-methylcytosine(5mC)and a significant increase in the level of 5-hydroxymethylcytosine(5hmC)in the kidney in CSD group.Regarding RNA modifications,we observed an overall increased trend for most of these significantly changed modifications across six tis-sues in CSD group.Our study sheds light on the significance of DNA and RNA modifications as crucial epigenetic markers in the context of CSD-induced stress.

Surface modification of small intestine submucosa in tissue engineering

With the development of tissue engineering,the required biomaterials need to have the ability to promote cell adhesion and proliferation in vitro and in vivo.Especially,surface modification of the scaffold material has a great influence on biocompatibility and functionality of materials.The small intestine submucosa(SIS)is an extracellular matrix isolated from the submucosal layer of porcine jejunum,which has good tissue mechanical properties and regenerative activity,and is suitable for cell adhesion,proliferation and differentiation.In recent years,SIS is widely used in different areas of tissue reconstruction,such as blood vessels,bone,cartilage,bladder and ureter,etc.This paper discusses the main methods for surface modification of SIS to improve and optimize the performance of SIS bioscaffolds,including functional group bonding,protein adsorption,mineral coating,topography and formatting modification and drug combination.In addition,the reasonable combination of these methods also offers great improvement on SIS surface modification.This article makes a shallow review of the surface modification of SIS and its application in tissue engineering.

小核酸类药物的修饰和靶向递送研究进展

小核酸类药物是在基因水平上发挥作用的小RNA分子,包括小干扰RNA、反义寡核苷酸、核酸适配体、微RNA等。小核酸类药物研发中面临易被核酸酶降解、半衰期短、易被血液循环中的免疫细胞识别、跨膜转运困难等难题。利用化学修饰和末端修饰可提高小核酸的抗酶解能力和稳定性,延长半衰期,降低免疫原性,提高靶向性。利用核酸类药物载体可协助核酸类药物到达病灶,增加靶向性,并实现溶酶体逃逸,提高药效。常用的载体包括病毒载体、脂质体、无机纳米粒子、聚合物纳米粒子和外泌体等。本文综述小核酸药物的修饰和递送技术研究进展,探讨提高小核酸类药物药效和靶向性的策略,以期为小核酸类药物的临床应用转化提供参考。

m^(6)A修饰在非小细胞肺癌中作用的研究进展

肺癌是全世界常见的恶性肿瘤,也是恶性肿瘤导致死亡的常见原因。根据肺癌的分化程度和形态特征,目前将肺癌分为两大类,即小细胞肺癌和非小细胞肺癌(non-small-cell lung cancer,NSCLC),其中常见的是NSCLC,约占肺癌的85%^([1])。尽管近几十年来诊断和治疗技术得到了改进,但NSCLC的不良预后导致患者的五年生存率始终低于20%^([2]),严重危害人类健康,是人类未解决的难题,因此,还需要对其发生发展的分子机制有更深入的认识。近年,RNA的N^(6)-甲基腺嘌呤(N^(6)-methyladenosine,m^(6)A)修饰与肿瘤的关系得到了广泛关注,大量研究揭示m^(6)A修饰参与包括NSCLC在内的各种肿瘤的发生发展过程,本文总结了近年m^(6)A修饰各种相关调节因子在NSCLC中发挥的细胞生物学功能及分子机制的研究进展。

精密小模数非均布行星齿轮传动优化设计

本文以某款精密小模数行星传动齿轮箱为对象,分析了行星轮非对称分布时安装角的计算方法及步骤,对比了不同安装角对径向力的影响,提出了安装角尽量接近均匀分布安装角有助于最小化径向力,提高系统寿命。针对非均布传动进行修形优化,降低其传递误差波动,改善齿面接触斑偏载现象,进一步改善齿轮啮合质量,提高运行寿命。

大直径盾构小半径曲线掘进施工工艺技术研究

以广州琶洲支线项目盾构500m小半径曲线施工为例,对大直径泥水盾构小半径曲线隧道施工中的大盾构针对性改造、掘进轴线控制、管片姿态控制、地表沉降控制等技术难题进行研究,通过同步双液注浆、保持合适的掘进姿态,并使用深层位移监测手段对盾构掘进影响进行研究,归纳整理出相应的解决措施,保证了盾构施工质量。

降低竖炉带冷机故障及提升冷却效率的措施

新疆昕昊达矿业有限责任公司采用球团竖炉工艺,用带式冷却机对球团矿进行冷却,在生产运行中带冷机故障频繁,经常性非计划停机,设备作业率低,影响竖炉产能的发挥。带冷机主要存在轨道跑偏、漏料严重和小刮板掉道等问题。同时,因原篦子箅缝中卡球团,导致冷却效率降低。利用年修及定期检修对带冷机进行技术改造后,故障发生率降低了90%以上,冷却效率大幅提高。

植物嫁接诱导的遗传变异机理的研究进展

植物嫁接诱导的可遗传变异是一种普遍存在的现象,但是关于嫁接变异产生的条件及机制一直是国内外备受争议的研究课题之一。近年来,对于砧穗之间遗传物质的水平转移方面的研究取得了很大的进步。研究表明在嫁接植物体中,来自砧木的遗传信号物质能够通过胞间连丝和维管束转移到接穗中并调控接穗的生长发育模式。而且,一些非编码RNA还能通过表观遗传修饰改变植物的特性以应对嫁接冲击。文章主要从嫁接遗传变异的产生和维持机制两方面对最新的研究进展进行了系统地综述,这对于深入理解嫁接变异的机理具有一定意义。

杂种优势形成的表观遗传学研究进展

杂种优势是一种复杂的生物学现象,在农业生产上得到了广泛的应用,但对其形成的遗传机理和分子基础尚不清楚。随着表观遗传学的深入研究,尤其是DNA甲基化、小分子RNA和组蛋白修饰等技术的发展,为杂种优势形成的分子基础提供了新的研究策略和技术手段。DNA甲基化、小分子RNA、组蛋白三者在杂交种中水平的改变与杂种优势有着一定关系,同时,三者之间相互作用调节基因表达影响杂种优势。本文简述了近年来表观遗传学在杂种优势形成中的作用和遗传机制等方面的研究进展,并且提出了目前存在的问题和下一步的研究方向。本综述将有助于从表观遗传学的角度认识杂种优势的形成机理,从而促进对杂种优势的表观遗传学基础的理解及其在植物杂交育种上的应用研究。

化学修饰阳极氧化铝模板法合成小尺寸聚苯胺纳米线

利用表面活性剂对阳极氧化铝(AAO)模板进行化学修饰,发展了模板合成法,从而得到更小尺寸的聚苯胺纳米管、线.在表面活性剂十八烷基脂肪酸(R18)修饰下,在14nm孔径的AAO模板中合成7nm的纳米线.对不同表面活性剂的比较后发现,通过改变修饰表面活性剂上烷基链长可以对所制备的聚合物纳米管、线的直径进行调控.