63 research outputs found
Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice
We here report a genome-editing strategy to correct spinal muscular atrophy (SMA). Rather than directly targeting the pathogenic exonic mutations, our strategy employed Cas9 and guide-sgRNA for the targeted disruption of intronic splicing-regulatory elements. We disrupted intronic splicing silencers (ISSs, including ISS-N1 and ISS + 100) of survival motor neuron (SMN) 2, a key modifier gene of SMA, to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs. Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration. Furthermore, co-injection of Cas9 mRNA from Streptococcus pyogenes (SpCas9) or Cas9 from Staphylococcus aureus (SaCas9) alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56% and 100% of severe SMA transgenic mice (Smn , SMN2 ). The median survival of the resulting mice was extended to >400 days. Collectively, our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. -/- tg/
Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials
Imaging findings of superficial angiomyxoma in the eye socket
Key Clinical Message A 23‐year‐old male with a tumor in the eye socket was characterized by multimodal images, including ultrasonography, computed tomography, and magnetic resonance imaging. After admission, surgical resection of the tumor was performed and superficial angiomyxoma was confirmed. Two years later, this tumor recurred in the same location. Abstract Superficial angiomyxoma (SAM) is a rare benign neoplasm composed mostly of myxoid material that can affect many parts of the body in middle‐aged patients. Only a few case reports have involved imaging, which is extremely insufficient. Here, we present a case of SAM in the eye socket evaluated by imaging, including ultrasonography, computed tomography, and magnetic resonance imaging. The patient underwent surgical resection, and the diagnosis of SAM was confirmed. During the postoperative follow‐up, the tumor recurred in the same location without metastasis 2 years later
TRPC3 Is Dispensable for β-Alanine Triggered Acute Itch
Abstract The detection of pruritic (itchy) stimuli is mediated by a variety of receptors and channels expressed by primary sensory neurons. The G protein-coupled receptor (GPCR) MRGPRD is selectively expressed by a subset of mouse non-peptidergic nociceptors and functions as the molecular receptor for the itch-inducing chemical β-alanine. However, the channels responsible for generating electrical signals downstream of MRGPRD remain unclear. Here, we found that a member of the canonical TRP channel family, TRPC3, is highly expressed in MRGPRD+ non-peptidergic nociceptors, raising the possibility of whether TRPC3 functions as a downstream channel in the MRGPRD signaling pathway. We tested TrpC3 null mice for β-alanine induced itch, and found that these mice exhibit normal responses to β-alanine. At the cellular level, calcium influx triggered by β-alanine is also unchanged in cultured DRG neurons from TrpC3 null mice compared to wild type. Together, our results demonstrate that mouse TrpC3 is dispensable for β-alanine-induced acute itch
Detailed Structural, Spectroscopic, and Electrochemical Trends of Halido Mono- and Bis(NHC) Complexes of Au(I) and Au(III)
A complete series
of ten Au(I) and Au(III) NHC complexes of the
general formulas [Au<sup>I</sup>X(<sup><i>i</i></sup>Pr<sub>2</sub>-bimy)] (<b>1</b>–<b>3</b>, X = Cl, Br,
and I), [Au<sup>I</sup>(<sup><i>i</i></sup>Pr<sub>2</sub>-bimy)<sub>2</sub>]BF<sub>4</sub> (<b>4</b>), [Au<sup>III</sup>X<sub>3</sub>(<sup><i>i</i></sup>Pr<sub>2</sub>-bimy)]
(<b>5</b>–<b>7</b>, X = Cl, Br, and I) and <i>trans</i>-[Au<sup>III</sup>X<sub>2</sub>(<sup><i>i</i></sup>Pr<sub>2</sub>-bimy)]BF<sub>4</sub> (<b>8</b>–<b>10</b>, X = Cl, Br, and I) bearing the <sup><i>i</i></sup>Pr<sub>2</sub>-bimy ligand, and all three common halido ligands
have been synthesized and fully characterized. Detailed trends in
their NMR and UV–Vis spectroscopic properties have been studied,
and their electrochemical behavior have been probed by cyclic voltammetry.
The solid state molecular structures of all new complexes determined
by single crystal X-ray diffraction are also described
Detailed Structural, Spectroscopic, and Electrochemical Trends of Halido Mono- and Bis(NHC) Complexes of Au(I) and Au(III)
A complete series
of ten Au(I) and Au(III) NHC complexes of the
general formulas [Au<sup>I</sup>X(<sup><i>i</i></sup>Pr<sub>2</sub>-bimy)] (<b>1</b>–<b>3</b>, X = Cl, Br,
and I), [Au<sup>I</sup>(<sup><i>i</i></sup>Pr<sub>2</sub>-bimy)<sub>2</sub>]BF<sub>4</sub> (<b>4</b>), [Au<sup>III</sup>X<sub>3</sub>(<sup><i>i</i></sup>Pr<sub>2</sub>-bimy)]
(<b>5</b>–<b>7</b>, X = Cl, Br, and I) and <i>trans</i>-[Au<sup>III</sup>X<sub>2</sub>(<sup><i>i</i></sup>Pr<sub>2</sub>-bimy)]BF<sub>4</sub> (<b>8</b>–<b>10</b>, X = Cl, Br, and I) bearing the <sup><i>i</i></sup>Pr<sub>2</sub>-bimy ligand, and all three common halido ligands
have been synthesized and fully characterized. Detailed trends in
their NMR and UV–Vis spectroscopic properties have been studied,
and their electrochemical behavior have been probed by cyclic voltammetry.
The solid state molecular structures of all new complexes determined
by single crystal X-ray diffraction are also described
Removal Mechanisms and Microstructure Characteristics of Laser Paint Stripping on Aircraft Skin Surface
As a non-contact and non-destructive technology, laser cleaning provides an alternative method for the paint stripping of aircraft skins. Herein, the particular multi-layer paint on the aluminum alloy aircraft skin surface was stripped by adjusting laser parameters. Beyond expectation, multi-layer paint led to a highly complex surface as opposed to the ordinary single-layer paint after laser cleaning. The surface morphology, chemical compositions, and surface functional groups of the samples were analyzed, and the successful depaint parameters were found in this experiment with damage free of the aluminum substrate, i.e., laser energy density of 5.09 J/cm2 and scanning speed of 700 mm/s. More importantly, this paper revealed that the mechanisms of laser paint stripping from Al alloy aircraft skin are thermal decomposition, evaporation, and spallation. After laser cleaning, the surface nanoindentation hardness with paint completely stripped and undamaged was increased by 3.587% relative to that of the conventional mechanical lapping sample. The improvement of nanoindentation hardness was also confirmed by the microstructure characterized with electron backscatter diffraction (EBSD) in which plastic deformation led to strain hardening of the substrate surface. This study lays a solid foundation for large-scale, high-efficiency, and low-pollution removal of more complex paint layers on aircraft surfaces in the future
Anti-Biofilm Activities of Chinese Poplar Propolis Essential Oil against Streptococcus mutans
Streptococcus mutans (S. mutans) is a common cariogenic bacterium that secretes glucosyltransferases (GTFs) to synthesize extracellular polysaccharides (EPSs) and plays an important role in plaque formation. Propolis essential oil (PEO) is one of the main components of propolis, and its antibacterial activity has been proven. However, little is known about the potential effects of PEO against S. mutans. We found that PEO has antibacterial effects against S. mutans by decreasing bacterial viability within the biofilm, as demonstrated by the XTT assay, live/dead staining assay, LDH activity assay, and leakage of calcium ions. Furthermore, PEO also suppresses the total of biofilm biomasses and damages the biofilm structure. The underlying mechanisms involved may be related to inhibiting bacterial adhesion and GTFs activity, resulting in decreased production of EPSs. In addition, a CCK8 assay suggests that PEO has no cytotoxicity on normal oral epithelial cells. Overall, PEO has great potential for preventing and treating oral bacterial infections caused by S. mutans
Enzyme Activities in the Lignin Metabolism of Chinese Olive (Canarium album) with Different Flesh Characteristics
Lignin is crucial to the formation of fruit texture quality. Here, we aimed to explore the relationship between lignin metabolism and fruit texture by investigating the lignin content, total phenols and their related enzyme activities among three Chinese olive (Canarium album (Lour.) Raeusch) genotypes. Our results showed that lignin deposition moved from the exocarp to the flesh in Chinese olive fruit. The lignin, total phenols and enzyme activities were all different between the three Chinese olive cultivars at each developmental stage. The lignin content was positively correlated with the PAL, 4CL and POD activities. These results demonstrated that lignin metabolism was regulated through the related enzyme activities. Therefore, our findings may provide insight to facilitate further improvement in fruit texture quality in Chinese olive
Enzyme Activities in the Lignin Metabolism of Chinese Olive (<i>Canarium album</i>) with Different Flesh Characteristics
Lignin is crucial to the formation of fruit texture quality. Here, we aimed to explore the relationship between lignin metabolism and fruit texture by investigating the lignin content, total phenols and their related enzyme activities among three Chinese olive (Canarium album (Lour.) Raeusch) genotypes. Our results showed that lignin deposition moved from the exocarp to the flesh in Chinese olive fruit. The lignin, total phenols and enzyme activities were all different between the three Chinese olive cultivars at each developmental stage. The lignin content was positively correlated with the PAL, 4CL and POD activities. These results demonstrated that lignin metabolism was regulated through the related enzyme activities. Therefore, our findings may provide insight to facilitate further improvement in fruit texture quality in Chinese olive
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