BACKGROUND & AIMS: :During normal muscle shortening, the myosin heads must undergo many cycles of interaction with the actin filaments sliding past them. It is important to determine what range of configurations is found under these circumstances, and, in terms of the tilting lever arm model, what range of orientations the lever arms undergo. We have studied this using the X-ray interference technique described in the previous article, focusing mainly on the changes in the first order meridional reflection (M3) as compared to isometric. The change in ratio of the heights of the interference peaks indicates how far the mean lever arm angle has moved towards the end of the working stroke; the total intensity change depends on the angle change, on the number of heads now attached at any one time, and on the dispersion of lever arm angles. The latter provides a measure of the distance over which myosin heads remain attached to actin as they go through their working strokes. Surprisingly, the mean position of the attached heads moves only about 1 nm inwards (towards the center of the A-band) at low velocity shortening (around 0.9 T0): their dispersion changes very little. This shows that they must be detaching very early in the working stroke. However, at loads around 0.5 T0, the mean lever arm angle is about half way towards the end of the working stroke, and the dispersion of lever arm angles (with a uniform dispersion) is such as to distribute the heads throughout the whole of the working stroke. At higher velocities of shortening (at 0.3 T0), the mean position shifts further towards the end of the stroke, and the dispersion increases further. The details of the measurements, together with other data on muscle indicate that the force-generating mechanism within the myosin heads must have some unexpected properties.

背景与目标： ：在正常的肌肉缩短过程中，肌球蛋白的头部必须经历许多循环，肌动蛋白丝会滑过它们。重要的是确定在这些情况下找到的配置范围，以及就倾斜杠杆臂模型而言，杠杆臂所经历的定向范围。我们已经使用前一篇文章中描述的X射线干涉技术对此进行了研究，主要关注与等轴测图相比一阶子午反射（M3）的变化。干涉峰的高度之比的变化表示平均杠杆臂角度已向工作行程末端移动了多大；总的强度变化取决于角度变化，取决于现在任一时刻已安装的磁头数量以及杠杆角度的偏差。后者提供了肌球蛋白头经过工作行程时肌动蛋白头保持附着在肌动蛋白上的距离的量度。令人惊讶的是，在低速缩短（大约0.9 T0）时，连接头的平均位置仅向内（向A波段中心）移动约1 nm：它们的色散变化很小。这表明它们必须在工作冲程的很早就分离。但是，在大约0.5 T0的载荷下，平均杠杆臂角度约为工作行程终点的一半，并且杠杆臂角度的偏差（具有均匀的偏差）可以使磁头分布在整个液压缸中。工作行程。在较高的缩短速度下（在0.3 T0时），平均位置会进一步向冲程末端移动，并且色散会进一步增加。测量的详细信息以及有关肌肉的其他数据表明，肌球蛋白头部内的力产生机制必须具有一些意外的特性。

BACKGROUND & AIMS: :Cognitive-motor interference (CMI) is evident when simultaneous performance of a cognitive task and a motor task results in deterioration in performance in one or both of the tasks, relative to performance of each task separately. The purpose of this review is to present a framework for categorizing patterns of CMI and to examine the specific patterns of CMI evident in published studies comparing single-task and dual-task performance of cognitive and motor tasks during gait and balance activities after stroke. We also examine the literature for associations between patterns of CMI and a history of falls, as well as evidence for the effects of rehabilitation on CMI after stroke. Overall, this review suggests that during gait activities with an added cognitive task, people with stroke are likely to demonstrate significant decrements in motor performance only (cognitive-related motor interference), or decrements in both motor and cognitive performance (mutual interference). In contrast, patterns of CMI were variable among studies examining balance activities. Comparing people poststroke with and without a history of falls, patterns and magnitude of CMI were similar for fallers and nonfallers. Longitudinal studies suggest that conventional rehabilitation has minimal effects on CMI during gait or balance activities. However, early-phase pilot studies suggest that dual-task interventions may reduce CMI during gait performance in community-dwelling stroke survivors. It is our hope that this innovative and critical examination of the existing literature will highlight the limitations in current experimental designs and inform improvements in the design and reporting of dual-task studies in stroke.

背景与目标： ：当同时执行一项认知任务和一项运动任务导致一项或两项任务的绩效相对于每项任务的绩效下降时，认知运动干扰（CMI）显而易见。这篇综述的目的是提供一个用于对CMI模式进行分类的框架，并检查已发表的研究中明显的CMI特定模式，该研究比较了中风后步态和平衡活动期间认知和运动任务的单任务和双任务表现。我们还检查了CMI模式与跌倒历史之间的关联的文献，以及中风后CMI康复的影响的证据。总的来说，这项研究表明，在具有额外认知任务的步态活动中，中风患者可能仅表现出运动能力的显着下降（与认知有关的运动干扰），或者运动和认知能力的下降（相互干扰）。相反，在研究平衡活动的研究中，CMI的模式是可变的。比较有或没有跌倒历史的人的中风后，跌倒者和非跌倒者的CMI模式和强度相似。纵向研究表明，传统的康复在步态或平衡活动期间对CMI的影响最小。但是，早期阶段的初步研究表明，双任务干预可能会降低社区居民卒中幸存者步态表现期间的CMI。我们希望对现有文献进行的创新和批判性检查将凸显当前实验设计的局限性，并为中风双重任务研究的设计和报告提供改进的信息。

BACKGROUND & AIMS: :Known methods of testing for interference in human genetic maps are reviewed. Two aspects of interference are distinguished, numerical interference referring to the numbers of crossovers occurring and positional interference referring to the positions of crossovers. Tests for interference generally address only one or the other of these two aspects. Published investigations of interference presume fully informative marker maps, while in reality genetic markers are of limited heterozygosity, which weakens some of the tests for interference. The conclusion is drawn that rigorous tests for interference have not yet been carried out for human data.

背景与目标： 综述了检测人类遗传图谱中干扰的已知方法。区分了干扰的两个方面，数字干扰是指发生的交叉次数，位置干扰是指交叉的位置。干扰测试通常仅针对这两个方面中的一个或另一个。公开发表的对干扰的研究假定具有充分信息的标记图，而实际上，遗传标记的杂合度有限，这削弱了一些干扰测试。结论是，尚未对人类数据进行严格的干扰测试。

BACKGROUND & AIMS: BACKGROUND:Perchlorate-induced natrium-iodide symporter (NIS) interference is a well-recognized thyroid disrupting mechanism. It is unclear, however, whether a chronic low-dose exposure to perchlorate delivered by food and drinks may cause thyroid dysfunction in the long term. Thus, the aim of this review was to overview and summarize literature results in order to clarify this issue. METHODS:Authors searched PubMed/MEDLINE, Scopus, Web of Science, institutional websites and Google until April 2020 for relevant information about the fundamental mechanism of the thyroid NIS interference induced by orally consumed perchlorate compounds and its clinical consequences. RESULTS:Food and drinking water should be considered relevant sources of perchlorate. Despite some controversies, cross-sectional studies demonstrated that perchlorate exposure affects thyroid hormone synthesis in infants, adolescents and adults, particularly in the case of underlying thyroid diseases and iodine insufficiency. An exaggerated exposure to perchlorate during pregnancy leads to a worse neurocognitive and behavioral development outcome in infants, regardless of maternal thyroid hormone levels. DISCUSSION AND CONCLUSION:The effects of a chronic low-dose perchlorate exposure on thyroid homeostasis remain still unclear, leading to concerns especially for highly sensitive patients. Specific studies are needed to clarify this issue, aiming to better define strategies of detection and prevention.

背景与目标： 背景：高氯酸盐诱导的碘碘化钠共转运蛋白（NIS）干扰是公认的甲状腺破坏机制。然而，目前尚不清楚从食物和饮料中长期摄入低剂量的高氯酸盐是否会长期导致甲状腺功能障碍。因此，本综述的目的是概述和总结文献结果，以阐明该问题。
方法：作者搜索PubMed / MEDLINE，Scopus，Web of Science，机构网站和Google直到2020年4月，以获取有关口服食用高氯酸盐化合物引起的甲状腺NIS干扰的基本机制及其临床后果的相关信息。
结果：食物和饮用水应被视为高氯酸盐的相关来源。尽管存在一些争议，但横断面研究表明，高氯酸盐暴露会影响婴儿，青少年和成人的甲状腺激素合成，特别是在潜在的甲状腺疾病和碘不足的情况下。妊娠期间过度暴露于高氯酸盐会导致婴儿的神经认知和行为发育恶化，无论母亲的甲状腺激素水平如何。
讨论与结论：长期低剂量高氯酸盐暴露对甲状腺体内稳态的影响仍不清楚，尤其是对高度敏感的患者引起关注。需要进行专门的研究来澄清此问题，以更好地定义检测和预防策略。

BACKGROUND & AIMS: CONTEXT:Heterophilic antibodies are a well-described interferent but poorly appreciated and are often not a recognized problem affecting most immunoassays. We describe for the first time heterophilic antibodies interference affecting an adrenocorticotropic hormone (ACTH) assay in a patient with Cushing's syndrome due to bilateral nodular adrenal hyperplasia. CASE:A 60-year-old retired female nurse underwent extensive invasive investigations, which were ultimately unnecessary, as a result of initial analytical interference in the ACTH assay, which could not be resolved using a proprietary heterophilic binding reagent. RESULTS:This case highlights the inherent difficulty of diagnosing Cushing's syndrome and the large emphasis placed on laboratory tests. The consequence of not initially identifying interference in this patient's laboratory test results led to unnecessary and costly investigations with potentially adverse outcomes. CONCLUSIONS:Clinicians and the laboratory community need to be continuously vigilant and view laboratory results with caution when they are inconsistent with the clinical picture. This approach is paramount, especially at a time of increasing automation and ever-diminishing scientist involvement in sample processing.

背景与目标： 背景：嗜异性抗体是一种被很好描述的干扰物，但人们对其了解不多，并且通常不是公认的影响大多数免疫测定的问题。我们首次描述了由于双侧结节性肾上腺皮质增生而影响库欣综合征的患者中的促肾上腺皮质激素（ACTH）测定中的嗜异性抗体干扰。
案例：一名60岁的退休女护士接受了广泛的侵入性检查，由于ACTH分析中存在最初的分析干扰，最终没有必要进行此项检查，而使用专用的异源结合试剂无法解决该问题。
结果：该病例突出了诊断库欣氏综合症的固有困难，并着重于实验室检查。最初没有识别出对该患者实验室检查结果的干扰，其结果导致不必要且昂贵的调查，并可能产生不利的后果。
结论：临床医生和实验室界需要保持警惕，并在与临床情况不一致时谨慎观察实验室结果。这种方法至关重要，尤其是在自动化程度不断提高且科学家对样品处理的参与不断减少的时候。

BACKGROUND & AIMS: :We assessed age differences in interference effects in priming by using fragment completion. In Experiment 1, noninterfering filler words preceded critical targets at study, and priming was age invariant. In Experiment 2, the same target items had interfering competitors at the beginning of the list, such that both the target and the competitor were legitimate solutions to a fragment. Having two responses to a cue was disruptive for older adults, but not for younger adults. Younger and older adults differ in their susceptibility to interference in implicit tasks, and interference may play a role in influencing the magnitude of age differences in priming.

背景与目标： ：我们使用片段完成方法评估了引发作用中干扰作用的年龄差异。在实验1中，在研究中，关键词之前没有干扰的填充词，并且启动词是年龄不变的。在实验2中，相同的目标项目在列表的开头具有干扰的竞争者，因此目标和竞争者都是碎片的合法解决方案。对提示有两种反应会对老年人造成破坏，但对年轻人则没有影响。年轻人和老年人在隐性任务中对干扰的敏感性不同，并且干扰可能会影响启动时年龄差异的大小。

BACKGROUND & AIMS: :Near field scanning optical microscopy exploiting differential interference contrast enhancement is demonstrated. Beam splitting in the near field region is implemented using a dual color probe based on plasmonic color sorter idea. This provides the ability to illuminate two neighboring points on the sample simultaneously. It is shown that by modulating the two wavelengths employed in exciting such a probe, phase difference information can be retrieved through measuring the near field photoinduced force at the difference of the two modulation frequencies. This difference in frequency is engineered to correspond to the first resonant frequency of the cantilever, resulting in improved SNR, and sensitivity. The effect of both topographical and material changes in the proposed near field differential interference (NFDIC) technique are investigated for CNT and silica samples. This method is a promising technique for high contrast and high spatial resolution microscopy.

背景与目标： ：展示了利用差分干涉对比增强的近场扫描光学显微镜。使用基于等离激元颜色分类器思想的双色探针实现近场区域中的光束分离。这提供了同时照射样品上两个相邻点的能力。示出了通过调制在激发这样的探针中使用的两个波长，可以通过在两个调制频率的差处测量近场光感应力来检索相差信息。将该频率差设计为与悬臂的第一共振频率相对应，从而提高了SNR和灵敏度。对于碳纳米管和二氧化硅样品，研究了拟议的近场微分干涉（NFDIC）技术中形貌和材料变化的影响。该方法是用于高对比度和高空间分辨率显微镜的有前途的技术。

BACKGROUND & AIMS: :A recently developed multiple-beam interference microscopic technique has been used to visualize submicroscopic structures of Entamoeba histolytica and their movements in applied external electric fields. The movements were videorecorded and it was found that at low current (120 microA) pseudopods are filled with hyaline ectoplasm. At slightly higher current (about 150 microA), the amoeba stops extending the pseudopods and loosens its attachment to the surface. At higher currents (200 microA), it forms a cyst and remains immobile for a time. Before this stage is reached a narrow ring is formed around the nucleus due to alterations in the proteins to protect it.

背景与目标： ：最近开发的多光束干涉显微技术已用于可视化组织变形虫亚显微结构及其在外加电场中的运动。对运动进行了录像，发现在低电流（120微安）下，假足充满了透明的种质。在稍高的电流（约150微安）下，变形虫停止延伸假足，并使其与表面的附着变松。在更高的电流（200微安）下，它会形成一个囊肿，并在一段时间内保持静止。在此阶段之前，由于保护蛋白质的改变，在核周围形成了一个狭窄的环。

BACKGROUND & AIMS: :This report provides a brief tutorial on the underlying physical forces that lead to interference with hearing aids and assistive listening devices, as well as measurement issues and possible solutions to the problem.

背景与目标： ：此报告提供了简短的教程，介绍了导致助听器和辅助听力设备受到干扰的潜在物理力，以及测量问题和对该问题的可能解决方案。

BACKGROUND & AIMS: :Although natural images often include discordant information about object boundaries, the majority of research on texture segmentation has involved variation along a single dimension, e.g. colour, orientation, size. In this study, we examined orientation-based texture segmentation in the presence and absence of task-irrelevant colour variation. Previously, it had been shown that orientation-based texture segmentation was impaired if the elements, normally of one colour, were randomly allocated one of two colours (Morgan et al, 1992 Proceedings of the Royal Society of London, Series B 248 291-295). We found that this interference disappeared, however, when the spatial pattern of the colour variation was regular, as opposed to random, and when the elements were randomly positioned. We consider four models of how relevant and irrelevant texture information might combine to produce the interference effect, with special regard to these new findings. None of the models could account for the dependency of the interference effect on the spatial arrangement of colour and orientation in the texture. We suggest that inter-element separation and spatial-frequency selectivity are critical variables in the interference effect.

背景与目标： ：虽然自然图像通常包含有关对象边界的不一致信息，但是大多数纹理分割研究都涉及沿单个维度的变化，例如颜色，方向，大小。在这项研究中，我们在存在和不存在与任务无关的颜色变化的情况下，检查了基于方向的纹理分割。以前的研究表明，如果通常将一种颜色的元素随机分配为两种颜色中的一种，则基于方向的纹理分割会受到损害（Morgan等人，《伦敦皇家学会学报，1992年》，系列B 248 291-295 ）。我们发现，当颜色变化的空间模式是规则的而不是随机的并且元素是随机放置时，这种干扰消失了。我们考虑了四个模型，这些模型将相关和不相关的纹理信息如何组合以产生干扰效果，并特别注意这些新发现。这些模型都无法说明干涉效应对纹理的颜色和方向的空间排列的依赖性。我们建议元素间分离和空间频率选择性是干扰效应中的关键变量。

BACKGROUND & AIMS: OBJECTIVE:To examine the relationships between a new scale, the Eating and Body Image Disturbances Academic Interference Scale (EBIDAIS), and measures of eating disturbance, body image, and academic achievement. METHOD:One thousand five hundred eighty-four college undergraduates completed the measures in an online survey and were awarded class credit for their participation. Measures included the Eating Disorder Inventory Bulimia, Drive for Thinness, Body Dissatisfaction, and Perfectionism subscales. Grade point average (GPA) was also reported. RESULTS:Academic interference and GPA were significantly correlated, indicating that higher interference scores were related to lower GPA. EBIDAIS was also significantly correlated with drive for thinness, bulimia, and body dissatisfaction, but was not significantly associated with perfectionism. The correlation between interference and GPA was substantially higher for a subsample of individuals who scored in the elevated range on eating and body dissatisfaction. CONCLUSION:Academic interference may be a relatively unexamined, but potentially important, outcome for individuals who experience eating problems and body image disturbance.

背景与目标： 目的：研究一种新的量表，饮食和身体图像干扰学术干扰量表（EBIDAIS）与饮食干扰，身体图像和学习成绩之间的关系。
方法：154名大学生完成了在线调查中的各项措施，并因参与而获得了课程信用。措施包括饮食失调清单贪食症，追求瘦身，身体不满和完美主义分量表。还报告了平均绩点（GPA）。
结果：学术干扰与GPA显着相关，表明较高的干扰评分与较低的GPA相关。 EBIDAIS与瘦弱，贪食症和身体不满的动机也有显着相关性，但与完美主义没有显着相关性。对于饮食和身体不满意评分在较高范围内的个人子样本，干扰与GPA之间的相关性显着更高。
结论：对于经历饮食问题和身体形象障碍的个人，学术干扰可能是相对未经检查的，但可能很重要。

BACKGROUND & AIMS: BACKGROUND & AIMS:Oestrogen and oestrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS:Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate half maximal inhibitory concentration values. To dissect how 17β-estradiol interferes with phases of hepatitis C virus life cycle, its effects were measured on the hepatitis C virus pseudo-particle system (viral entry), the subgenomic replicon N17/JFH1 and the replicon cell line Huh7-J17 (viral replication). Finally, in a dual-step infection model, infectious supernatants, collected from infected cells exposed to hormones, were used to infect naïve cells. RESULTS:Progesterone and testosterone showed no inhibitory effect on hepatitis C virus; dehydroepiandrosterone was only mildly inhibitory. In contrast, 17β-estradiol inhibited infection by 64%-67% (IC50 values 140-160 nmol/L). Fulvestrant reverted the inhibition by 17β-estradiol in a dose-dependent manner. 17β-estradiol exerted only a slight inhibition (<20%) on hepatitis C virus pseudo-particles, and had no effect on cells either transiently or stably (Huh7-J17 cells) expressing the N17/JFH1 replicon. In the dual-step infection model, a significant half maximal inhibitory concentration decline occurred between primary (134 nmol/L) and secondary (100 nmol/L) infections (P=.02), with extracellular hepatitis C virus RNA and infectivity being reduced to a higher degree in comparison to its intracellular counterpart. CONCLUSIONS:17β-estradiol inhibits hepatitis C virus acting through its intracellular receptors, mainly interfering with late phases (assembly/release) of the hepatitis C virus life cycle.

背景与目标： 背景与目的：雌激素和雌激素介导的信号转导机制尚不完全清楚，可预防丙型肝炎病毒。我们旨在确定丙型肝炎病毒生命周期的哪个阶段受到雌激素的影响。
方法：将感染JFH1病毒（基因型2a）的Huh7细胞暴露于脱氢表雄酮，睾丸激素，孕酮和17β-雌二醇（经/不经其受体拮抗剂氟维司汀测试）。建立剂量反应曲线以计算最大抑制浓度的一半。为了剖析17β-雌二醇如何干扰丙型肝炎病毒生命周期的各个阶段，测量了其对丙型肝炎病毒假颗粒系统（病毒进入），亚基因组复制子N17 / JFH1和复制子细胞系Huh7-J17（病毒）的影响。复制）。最后，在两步感染模型中，从暴露于激素的感染细胞中收集的感染上清液被用于感染幼稚细胞。
结果：孕酮和睾丸激素对丙型肝炎病毒无抑制作用。脱氢表雄酮仅具有轻度抑制作用。相比之下，17β-雌二醇可将感染抑制64％-67％（IC50值为140-160nmol / L）。氟韦斯特兰以剂量依赖的方式逆转了17β-雌二醇的抑制作用。 17β-雌二醇仅对C型肝炎病毒假颗粒产生轻微抑制作用（<20％），对表达N17 / JFH1复制子的细胞（瞬时或稳定）（Huh7-J17细胞）没有影响。在双步感染模型中，主要（134nmol / L）和继发性（100nmol / L）感染（P = .02）之间出现最大抑制浓度显着降低一半（P = .02），细胞外丙型肝炎病毒RNA和感染力降低与细胞内对应物相比，程度更高。
结论：17β-雌二醇通过其细胞内受体抑制丙型肝炎病毒，主要干扰丙型肝炎病毒生命周期的后期阶段（组装/释放）。

BACKGROUND & AIMS: :Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma with poor prognosis. Its hallmark is the translocation t(11:14)q (13;32), leading to overexpression of cyclin D1, a positive regulator of the cell cycle. As cyclin D1 up-regulation is not sufficient for inducing malignant transformation, we combined DNA microarray and RNA interference (RNAi) approaches to identify novel deregulated genes involved in the progression of MCL. DNA microarray analysis identified 46 genes specifically up-regulated in MCL compared with normal B cells; 20 of these were chosen for further studies based on their cellular functions, such as growth and proliferation. The Granta 519 cell line was selected as an MCL in vitro model, to set up the RNAi protocol. To confirm the functionality of overexpression of the 20 disease-associated genes, they were knocked down using small interfering RNAs (siRNAs). In particular, knockdown of 3 genes, encoding the hepatoma-derived growth factor related protein 3 (HDGFRP3), the frizzled homolog 2 (FZD2), and the dual specificity phosphatase 5 (DUSP5), induced proliferative arrest in Granta 519 MCL cells. These genes emerged as functionally associated in MCL, in relation to growth and survival, and interfering with their function would increase insight into lymphoma growth regulation, potentially leading to novel clinical intervention modalities.

背景与目标： ：套细胞淋巴瘤（MCL）是非霍奇金淋巴瘤，预后较差。它的标志是易位t（11:14）q（13; 32），导致细胞周期蛋白D1（细胞周期的正向调节剂）的过表达。由于细胞周期蛋白D1的上调不足以诱导恶性转化，因此我们结合了DNA微阵列和RNA干扰（RNAi）方法来鉴定参与MCL进展的新型失调基因。 DNA微阵列分析鉴定出与正常B细胞​​相比在MCL中特异性上调的46个基因；根据它们的细胞功能（例如生长和增殖），选择了其中的20种进行进一步研究。选择Granta 519细胞系作为MCL体外模型，以建立RNAi方案。为了确认20种与疾病相关的基因过表达的功能，使用小型干扰RNA（siRNA）将它们敲低了。特别是敲除3个编码肝癌衍生的生长因子相关蛋白3（HDGFRP3），卷曲的同源物2（FZD2）和双重特异性磷酸酶5（DUSP5）的基因，可在Granta 519 MCL细胞中诱导增殖性停滞。这些基因在MCL中以与生长和存活有关的功能出现，并且干扰它们的功能将增加对淋巴瘤生长调节的了解，可能导致新的临床干预方式。

BACKGROUND & AIMS: :Exosomes are naturally occurring extracellular vesicles released by most mammalian cells in all body fluids. Exosomes are known as key mediators in cell-cell communication and facilitate the transfer of genetic and biochemical information between distant cells. Structurally, exosomes are composed of lipids, proteins, and also several types of RNAs which enable these vesicles to serve as important disease biomarkers. Moreover, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Recently, increasing attention has been focused on exosomes for the delivery of drugs, including therapeutic recombinant proteins, to various target tissues. Exosomes are also promising vehicles for the delivery of microRNAs and small interfering RNAs, which is usually hampered by rapid degradation of these RNAs, as well as inefficient tissue specificity of currently available delivery strategies. This review highlights the most recent accomplishments and trends in the use of exosomes for the delivery of drugs and therapeutic RNA molecules.

背景与目标： ：外来体是大多数哺乳动物细胞在所有体液中释放的天然存在的细胞外囊泡。外来体被称为细胞-细胞通讯中的关键介体，可促进远距离细胞之间遗传和生化信息的转移。在结构上，外泌体由脂质，蛋白质以及几种类型的RNA组成，这些RNA使这些囊泡可以用作重要的疾病生物标记。此外，由于外来体相对于常规的递送系统具有多种优势，因此已成为新型的药物和基因递送工具。近来，越来越多的注意力集中在用于将药物，包括治疗性重组蛋白，递送至各种靶组织的外泌体。外来体也是用于递送微小RNA和小的干扰RNA的有希望的载体，其通常由于这些RNA的快速降解以及当前可用的递送策略的低效率的组织特异性而受到阻碍。这篇综述着重介绍了使用外泌体递送药物和治疗性RNA分子的最新成就和趋势。

BACKGROUND & AIMS: AIMS:A switch in gene expression from MAT1A to MAT2A was found in liver cancer, suggesting that MAT2A plays an important role in facilitating cancer growth. MAT2A is an interesting target for antineoplastic therapy. The molecular mechanisms of silencing MAT2A by RNA interference inhibited cell growth and induced apoptosis in hepatoma cells was studied. METHODS:We investigated the effects of MAT2A on S-adenosyl-methionine (SAM) production, cell growth and apoptotic cell death in hepatoma cell lines (Bel-7402, HepG2, and Hep3B) using an RNA interference approach. RESULTS:The treatment of three hepatoma cell lines with small interfering RNA (siRNA) targeting to the MAT2A gene resulted in reducing the MAT II activity, facilitating SAM production, increasing SAM : SAH ratio, inhibiting cell growth and inducing cell apoptosis in hepatoma cells. In addition, silencing MAT2A gene resulted in the stimulation of MAT1A mRNA production, which was blocked by 3-deazaadenosine and l-ethionine, but not d-ethionine, suggesting that such effect was specific and mediated by upregulation of SAM level and SAM : S-adenosylethionine (SAH) ratio. CONCLUSION:Silencing MAT2A by sequence-specific small interfering RNA caused a switch of MAT gene expression from MAT2A to MAT1A, which led the content of SAM to change to a higher steady-state level that resulted in the inhibition of cell growth and the induction of apoptotic cell death in human hepatoma cells. These results also suggested that MAT2A may hold potential as a new target for liver cancer gene therapy.

背景与目标： 目的：在肝癌中发现了从MAT1A到MAT2A的基因表达转换，这表明MAT2A在促进癌症生长中起着重要作用。 MAT2A是抗肿瘤治疗的一个有趣目标。研究了RNA干扰沉默MAT2A抑制肝癌细胞生长并诱导其凋亡的分子机制。
方法：我们使用RNA干扰方法研究了MAT2A对肝癌细胞系（Bel-7402，HepG2和Hep3B）中S-腺苷甲硫氨酸（SAM）的产生，细胞生长和凋亡细胞死亡的影响。
结果：用靶向MAT2A基因的小干扰RNA（siRNA）处理三种肝癌细胞系可降低MAT II活性，促进SAM的产生，增加SAM：SAH的比例，抑制细胞生长并诱导肝癌细胞的细胞凋亡。此外，沉默MAT2A基因可刺激MAT1A mRNA的产生，该刺激被3-deazaadenosine和l-ethionine阻断，但未被d-ethionine阻断，这表明这种作用是特异的，并由SAM水平和SAM：S的上调介导。 -腺苷乙硫氨酸（SAH）比率。
结论：通过序列特异性小干扰RNA沉默MAT2A，导致MAT基因表达从MAT2A向MAT1A的转换，导致SAM的含量改变为较高的稳态水平，从而抑制了细胞的生长并诱导了细胞凋亡。人肝癌细胞中的凋亡细胞死亡。这些结果还表明，MAT2A可能具有作为肝癌基因治疗的新靶标的潜力。