Retroviral vectors show long‐term gene expression in gene therapy through the integration of transgenes into the human cell genome. Murine leukemia virus (MLV), a well‐studied gammaretrovirus, has ...been often used as a representative retroviral vector. However, frequent integrations of MLV‐based vectors into transcriptional start sites (TSSs) could lead to the activation of oncogenes by enhancer effects of the genetic components within the vectors. Therefore, the MLV integration preference for TSSs limits its wider use in clinical applications. To reduce the integration preference of MLV‐based vectors, we attempted to perturb the structure of the viral integrase that plays a key role in determining integration sites. For this goal, we inserted histones and leucine zippers, having DNA‐binding property, into internal sites of MLV integrase. This integrase engineering yielded multiple mutant vectors that showed significantly different integration patterns compared with that of wild‐type vector. Some mutant vectors did not prefer the key regulatory genomic domains of human cells, TSSs. Moreover, a couple of engineered vectors did not integrate into the genomic sites near the TSSs of oncogenes. Overall, this study suggests that structural perturbation of integrase is a simple way to develop safer MLV‐based retroviral vectors for use in clinical applications.
Frequent integrations of murine leukemia virus (MLV) vector into regulatory regions of the human genome may cause the transformation of cells to cancerous ones, thereby limiting its wider use in clinical applications. Yang and coworkers developed new MLV‐based vectors by inserting histones and leucine zippers into the viral integrase. The engineered vectors did not prefer regulatory regions of the human genome during integration. The improved safety of the vectors would link to structural perturbation of the viral integrase, which was caused by the protein insertion.
To evaluate the prevalence and risk factors of myopia in adult Korean population.
Population-based cross-sectional data of 3,398 subjects aged 19 to 49 years was obtained using the Korea National ...Health and Nutrition Examination Survey 2013-2014 (KNHANES VI). Data, including refractive errors and potential risk factors were analyzed. The prevalence and risk factors of myopia, low myopia, and high myopia-defined as a spherical equivalent (SEQ) ≤ -0.5 diopters (D), -6.0 D < SEQ <-0.5 D, and SEQ ≤ -6.0 D, respectively-were evaluated.
The prevalence of myopia and high myopia were 70.6 (standard error (SE), ±1.1)% and 8.0 (SE, ±0.6)%, respectively. In multivariable analysis, younger age, higher education (≥12 years), parental myopia, lower serum 25-hydroxyvitamin D (25(OH)D) concentration (<9 ng/mL), longer time spent on near work (≥3 hours/day), and higher white blood cell (WBC) count (5-8.9 x 103) were associated with increased prevalence of both myopia and high myopia. Serum 25(OH)D concentration of ≥ 9 ng/ml was significantly associated with decreased prevalence of high myopia in participants with near work of ≥3 hours/day, although the effect was not significant in myopia and low myopia.
The prevalence of myopia and high myopia in Korean adults was substantially high, which increased with decreasing age. In addition to parental myopia, the serum 25(OH)D concentration, near work and inflammation reflected by WBC counts may be associated with myopia.
Background and Aims
Mitochondrial double‐stranded RNA (mtdsRNA) and its innate immune responses have been reported previously; however, mtdsRNA generation and its effects on alcohol‐associated liver ...disease (ALD) remain unclear. Here, we report that hepatic mtdsRNA stimulates toll‐like receptor 3 (TLR3) in Kupffer cells through the exosome (Exo) to enhance interleukin (IL)‐17A (IL‐17A) production in ALD.
Approach and Results
Following binge ethanol (EtOH) drinking, IL‐17A production primarily increased in γδ T cells of wild‐type (WT) mice, whereas the production of IL‐17A was mainly facilitated by CD4+ T cells in acute‐on‐chronic EtOH consumption. These were not observed in TLR3 knockout (KO) or Kupffer cell–depleted WT mice. The expression of polynucleotide phosphorylase, an mtdsRNA‐restricting enzyme, was significantly decreased in EtOH‐exposed livers and hepatocytes of WT mice. Immunostaining revealed that mtdsRNA colocalized with the mitochondria in EtOH‐treated hepatocytes from WT mice and healthy humans. Bioanalyzer analysis revealed that small‐sized RNAs were enriched in EtOH‐treated Exos (EtOH‐Exos) rather than EtOH‐treated microvesicles in hepatocytes of WT mice and humans. Quantitative real‐time PCR and RNA sequencing analyses indicated that mRNA expression of mitochondrial genes encoded by heavy and light strands was robustly increased in EtOH‐Exos from mice and humans. After direct treatment with EtOH‐Exos, IL‐1β expression was significantly increased in WT Kupffer cells but not in TLR3 KO Kupffer cells, augmenting IL‐17A production of γδ T cells in mice and humans.
Conclusions
EtOH‐mediated generation of mtdsRNA contributes to TLR3 activation in Kupffer cells through exosomal delivery. Consequently, increased IL‐1β expression in Kupffer cells triggers IL‐17A production in γδ T cells at the early stage that may accelerate IL‐17A expression in CD4+ T cells in the later stage of ALD. Therefore, mtdsRNA and TLR3 may function as therapeutic targets in ALD.
Despite its highest theoretical capacity, the practical applications of the silicon anode are still limited by severe capacity fading, which is due to pulverization of the Si particles through volume ...change during charge and discharge. In this study, silicon nanoparticles are embedded in micron-sized porous carbon spheres (Si-MCS) via a facile hydrothermal process in order to provide a stiff carbon framework that functions as a cage to hold the pulverized silicon pieces. The carbon framework subsequently allows these silicon pieces to rearrange themselves in restricted domains within the sphere. Unlike current carbon coating methods, the Si-MCS electrode is immune to delamination. Hence, it demonstrates unprecedented excellent cyclability (capacity retention: 93.5% after 500 cycles at 0.8 A g–1), high rate capability (with a specific capacity of 880 mAh g–1 at the high discharge current density of 40 A g–1), and high volumetric capacity (814.8 mAh cm–3) on account of increased tap density. The lithium-ion battery using the new Si-MCS anode and commercial LiNi0.6Co0.2Mn0.2O2 cathode shows a high specific energy density above 300 Wh kg–1, which is considerably higher than that of commercial graphite anodes.
Background and purpose
The etiological distribution of oculomotor nerve palsy has varied amongst the studies. This study aimed to define the clinical features and underlying etiologies of isolated ...oculomotor nerve palsy by recruiting patients from all departments in a referral‐based university hospital.
Methods
The medical records of 672 patients who had a confirmed diagnosis of isolated oculomotor nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020 were reviewed. A proportion of the etiology of isolated oculomotor nerve palsy was also compared with that of patients pooled from the previous studies that were searched on PubMed in May 2022.
Results
The most common etiology was microvascular (n = 168, 26.5%), followed by vascular anomalies (n = 110, 17.4%), neoplastic (n = 86, 13.6%), inflammatory (n = 79, 12.5%), idiopathic (n = 60, 9.5%) and traumatic (n = 53, 8.4%). Neurologists were mainly involved in the management of microvascular and inflammatory oculomotor nerve palsies whilst ophthalmologists mainly participated in the care of idiopathic, neoplastic and traumatic palsies. Neurosurgeons mostly took care of oculomotor nerve palsy due to vascular anomalies.
Conclusions
The proportion of etiologies of isolated oculomotor nerve palsy may differ according to the specialties involved in the management. The results of previous studies on the etiological distribution of isolated oculomotor nerve palsy should be interpreted with this consideration.
Silicon has a great potential as an alternative to graphite which is currently used commercially as an anode material in lithium-ion batteries (LIBs) because of its exceptional capacity and ...reasonable working potential. Herein, a low-cost and scalable approach is proposed for the production of high-performance silicon–carbon (Si–C) hybrid composite anodes for high-energy LIBs. The Si–C composite material is synthesized using a scalable microemulsion method by selecting silicon nanoparticles, using low-cost corn starch as a biomass precursor and finally conducting heat treatment under C3H6 gas. This produces a unique nano/microstructured Si–C hybrid composite comprised of silicon nanoparticles embedded in micron-sized amorphous carbon balls derived from corn starch that is capsuled by thin graphitic carbon layer. Such a dual carbon matrix tightly surrounds the silicon nanoparticles that provides high electronic conductivity and significantly decreases the absolute stress/strain of the material during multiple lithiation-delithiation processes. The Si–C hybrid composite anode demonstrates a high capacity of 1800 mAh g–1, outstanding cycling stability with capacity retention of 80% over 500 cycles, and fast charge–discharge capability of 12 min. Moreover, the Si–C composite anode exhibits good acceptability in practical LIBs assembled with commercial LiNi0.6Co0.2Mn0.2O2 and LiNi0.80Co0.15Al0.05O2 cathodes.
In partially accommodative esotropia (PAET), prism glasses can correct small angles of residual esotropia but the long-term effect of prismatic correction alone without surgery has not been reported. ...We aimed to investigate the long-term outcome of prism glasses after full hypermetropic correction for PAET.
This retrospective, case-control study was performed for children aged 10 years or younger with a residual esotropia of ≤ 20 prism diopters (PD) after full hypermetropic correction who were fitted with prism glasses and followed-up for 3 years or more. Clinical characteristics and the angle of esodeviation were obtained at each follow-up examination. Successful motor outcome after 3 years of prismatic correction was determined if the residual angle of esotropia after full hypermetropic correction was ≤ 10PD. Patients who eventually weaned off prism glasses were noted.
Among 124 patients, 30.6% achieved success and 7.3% weaned off prism glasses after 3 years of prism-wear. Smaller amount of latent esodeviation (P = 0.001) revealed by prism adaptation and good fusional response at near with the Worth 4-dot test were significant prognostic factors of success by multivariate analysis (P = 0.033). After 3 years of wearing prism glasses, the rate of improvement in stereoacuity was higher in the Success group (60.5% vs 27.9%) (P = 0.001), however, there was no significant difference between the prism-weaned group and prism-wearing group within the Success group (P>0.05).
Prism glasses for small angle PAET can be a treatment option in patients who have a small angle of latent esodeviation revealed by prism adaptation and good sensory fusion at near. Otherwise, early surgery may be advisable as the majority of patients showed suboptimal outcome even after long-term prism-wear.
Background and Purpose
The etiologies of abducens nerve palsy have shown a large variability among studies. This study aimed to establish the clinical features and underlying etiologies of isolated ...abducens nerve palsy by recruiting patients from all departments in a referral‐based university hospital.
Methods
We reviewed the medical records of 807 patients with a confirmed diagnosis of isolated abducens nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. We also compared the proportion of etiology with that of the patients pooled from the previous studies.
Results
The most common etiology was microvascular (n = 296, 36.7%), followed by idiopathic (n = 143, 17.7%), neoplastic (n = 115, 14.3%), vascular anomalies (n = 82, 10.2%), inflammatory (n = 76, 9.4%), and traumatic (n = 35, 4.3%). Patients were mostly managed by ophthalmologists (n = 576, 71.4%), followed by neurologists (n = 479, 59.4%), emergency physicians (n = 278, 34.4%), neurosurgeons (n = 191, 23.7%), and others (n = 72, 8.9%). The proportion of etiology significantly differed according to the age and sex of the patients and the specialties involved in the management (p < 0.001). Compared to the pooled data from the previous reports, the current study showed a higher prevalence of microvascular cause but a lower occurrence of traumatic and neoplastic causes.
Conclusions
The results of previous studies on etiologic distribution of isolated abducens nerve palsy should be interpreted with consideration of the demographic features of patients recruited and the specialties involved.
•AgNO3 and bare AgNPs have similar toxicities whereas PVP-coating reduces the toxicity.•Different responses of mutants suggest the distinct toxic mechanism of AgNO3 and AgNPs.•AgNO3 and AgNPs induce ...oxidative stress-related mitochondrial DNA damage.
This study examined the effects of polyvinylpyrrolidone (PVP) surface coating and size on the organismal and molecular toxicity of silver nanoparticles (AgNPs) on the nematode, Caenorhabditis elegans. The toxicity of bare AgNPs and 8 and 38nm PVP-coated AgNPs (PVP8-AgNPs, PVP38-AgNPs) were compared. The toxicity of AgNO3 was also tested because ion dissolution and particle-specific effects are often important characteristics determining Ag nanotoxicity. Comparative toxicity across AgNO3 and the three different types of AgNPs was first evaluated using a C. elegans mortality test by a direct comparison of the LC50 values. Subsequently, mutant screening followed by oxidative stress, mitochondrial toxicity and DNA damage assays were carried out at equitoxic (LC10 and LC50) concentrations to further assess the toxicity mechanism of AgNO3 and AgNPs. AgNO3 and bare AgNPs had similar toxicities, whereas PVP coating reduced the toxicity of the AgNPs significantly. Of the PVP-AgNPs, the smaller NPs were more toxic. Different groups of mutants responded differently to AgNO3 and AgNPs, which indicates that their toxicity mechanism might be different. AgNO3 and bare AgNPs induced mitochondrial membrane damage. None of the silver materials tested caused detectable polymerase-inhibiting DNA lesions in either the nucleus or mitochondria as measured by a quantitative PCR assay, but AgNO3, bare AgNPs and PVP8-AgNPs induced oxidative DNA damage. These results show that coatings on the AgNPs surface and the particle size make a clear contribution to the toxicity of the AgNPs, and oxidative stress-related mitochondrial and DNA damage appear to be potential mechanisms of toxicity.
Zero-dimensional–two-dimensional (0D–2D) hybrid optoelectronic devices have demonstrated high sensitivity and high performance due to the high absorption coefficient of 0D materials with a tunable ...detection range and a high carrier transport property of 2D materials. However, the reported 0D–2D hybrid devices employ toxic nanomaterials as sensitizing layers, which can limit the practical applications. In this study, we first fabricated the 0D–2D hybrid photodetector using nontoxic InP quantum dots (QDs) as a light-absorbing layer and black phosphorus (BP) as a transport layer. The surface treatment using 1,2-ethanedithiol and thermal treatment were carried out to remove the surface long ligands of colloidal QDs, which can accelerate the charge injection of the photogenerated carriers through the interfaces between InP QDs and BP. The InP QDs/BP hybrid photodetector demonstrates a high responsivity of 1 × 109 A/W and detectivity of 4.5 × 1016 Jones at 0.05 μW cm–2 under 405 nm illumination. The results show that 0D–2D hybrid photodetectors based on III–V semiconducting QD materials can be optimized for high-performance photodetectors.
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