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Neurodevelopmental delay and intellectual disability (ID) can arise from numerous genetic defects. To date, variants in the EXOSC gene family have been associated with such disorders. Using next-generation sequencing (NGS), known and novel variants in this gene family causing autosomal recessive ID (ARID) have been identified in five Iranian families. By collecting clinical information on these families and comparing their phenotypes with previously reported patients, we further describe the clinical variability of ARID resulting from alterations in the EXOSC gene family, and emphasize the role of RNA processing dysregulation in ARID.  相似文献   
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4,4′-(1,4-phenylene)bis(2-(alkylamino)-3-nitro-4H-benzo[g]chromene-5,10-dione) and 4,4′-(1,4-phenylene)bis(2-(alkylamino)-3-nitropyrano[3,2-c]chromen-5(4H)-one) derivatives are synthesized by a one-pot, multi-component reaction of N-alkyl-1-(methylthio)-2-nitroethenamine (derived from the reaction of various amines and 1,1-bis(methylthio)-2-nitroethene) with terephthalaldehyde or isophthalaldehyde, and 2-hydroxy-1,4-naphthoquinone or 4-hydroxycoumarin in EtOH/H2O (85 : 15) as the solvent at 89 °C. Response surface methodology (RSM) is used to investigate the effect of reaction temperature and water content of aqueous ethanol on the product yields and reaction time. The notable features of this work are the optimization of reaction conditions with minimal experiments, absence of catalyst, good yields, simple work-up and the non-chromatographic purification of products.

One-pot synthesis of C2-symmetric chromene derivatives, which serve as building blocks to prepare liquid crystals with potential electrical or optical properties.  相似文献   
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Seropositivity for HSV reaches more than 70% within the world population, and yet no approved vaccine exists. While HSV1 is responsible for keratitis, encephalitis, and labialis, HSV2 carriers have a high susceptibility to other STD infections, such as HIV. Induction of antiviral innate immune responses upon infection depends on a family of pattern recognition receptors called Toll‐like receptors (TLR). TLRs bridge innate and adaptive immunity by sensing virus infection and activating antiviral immune responses. HSV adopts smart tricks to evade innate immunity and can also manipulate TLR signaling to evade the immune system or even confer destructive effects in favor of virus replication. Here, we review mechanisms by which HSV can trick TLR signaling to impair innate immunity. Then, we analyze the role of HSV‐mediated molecular cues, in particular, NF‐κB signaling, in promoting protective versus destructive effects of TLRs. Finally, TLR‐based therapeutic opportunities with the goal of preventing or treating HSV infection will be discussed.  相似文献   
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Atherosclerotic plaques may rupture without warning, causing fatal clinical events such as myocardial infarction and stroke. Degree of stenosis, which is the current criterion for assessment of atherosclerotic disease severity, has been observed to have poor correlation with plaque vulnerability. Under physiological conditions, plaque undertakes mechanical loadings due to blood pressure and flow. From the material view point, rupture possibly occurs when the extra loading exceeds the material strength of the plaque. Therefore, morphological and mechanical features should be considered in an integrated way for a more accurate assessment of plaque vulnerability and for identification of the at-risk patient. Biomechanical stress analysis is a technique that allows such comprehensive assessment. This article focuses on the mechanical stresses in the plaque structure, which are believed to be of greater magnitude than the associated wall shear stress and are thought to be more closely associated with plaque rupture. We discuss the basic mechanics that govern plaque behavior, the material properties of atherosclerotic tissues and the studies investigating the association between high biomechanical stresses and plaque rupture. Parameter studies investigating the effect of morphologic factors on the critical biomechanical stresses and limitations of current simulation models are also reviewed.  相似文献   
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