Serum alanine aminotransferase levels are closely associated with metabolic disturbances in apparently healthy young adolescents independent of obesity

Purpose Liver metabolism plays a pivotal role in the development of metabolic disorders. We aimed to investigate the clinical and laboratory risk factors associated with alanine aminotransferase (ALT) levels in young adolescents from an urban population in Korea. Methods A population of 120 apparently healthy adolescents aged 12–13 years was included in the cross-sectional design study; 58 were overweight or obese and 62 were of normal weight. We estimated anthropometric and laboratory measurements, including waist-to-height ratio, blood pressure, insulin sensitivity, aspartate aminotransferases (AST), ALT, and lipid profiles. Results The mean ages of the overweight or obese and normal weight participants were 12.9±0.3 and 13.0±0.3 years, respectively. Height, weight, body mass index, waist circumference, waist-to-height ratio, systolic and diastolic blood pressure, AST, ALT, total cholesterol, low-density lipoprotein-cholesterol, triglyceride, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR) score were significantly higher and the high-density lipoprotein-cholesterol and quantitative insulin-sensitivity check index were significantly lower in the overweight/obese participants in comparison to the normal-weight participants (all P<0.05). In multivariate linear regression analysis, waist-to-height ratio, systolic blood pressure, and HOMA-IR score were independently and positively associated with serum ALT levels. Conclusion Screening for ALT levels in adolescents may help to differentiate those at risk of metabolic abnormalities and thus prevent disease progression at an early age

High performance carbon nanotubes thin film transistors by selective ferric chloride doping

Single wall carbon nanotubes (SWNT) have been a significant research topic as active layers for thin film transistors (TFTs) due to their high charge carrier mobility beyond that of crystalline silicon. In this study, we report an effective approach to achieve a very high field-effect mobility and on/off ratio for solution processed semiconducting SWNT TFTs, by selective doping through contact with a thin ferric chloride (FeCl3) dopant layer. The semiconducting layer is formed by a double spin coating of the highly purified (&gt;99%) high pressure carbon mono oxide (HiPCO) SWNT sorted by wrapping of poly (3-dodecylthiophene-2,5-diyl) (P3DDT). In order to achieve effective hole injection from the top Au source electrode without increasing the off-state drain current, less purified (98-99%) SWNTs produced by the plasma discharge process sorted by wrapping of poly (9,9-di-n-dodecylfluorene) (PFDD) are formed on the top of HiPCO film. Significantly improved TFT performance is achieved by the insertion of a few nanometers of a FeCl3 dopant layer at the semiconductor-contact interface. A significant high hole field-effect of 48.35 +/- 3.11 cm(2)V(-1)s(-1) (bare: 6.18 +/- 0.87 cm(2)V(-1)s(-1)) with a reasonable on/off current ratio of 10(5), and low off current of similar to 80 pA, are obtained by controlling the concentration of FeCl3 dopant (thickness = 1.5 nm) at the contact. Mobility is improved further at 2.5 nm thickness of the FeCl3 dopant layer resulting in a hole mobility of 177 +/- 13.2 cm(2) V(-1)s(-1), an on/off ratio of 7.4 x 10(3), and off state current of 1.2 x 10(-9) A

Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor

Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and improve the efficiency of prime-editing. Herein, we introduce two strategies to improve the editing efficiency using proximal dead sgRNA and chromatin-modulating peptides. We used enhanced prime-editing to generate Igf2 mutant mice with editing frequencies of up to 47% and observed germline transmission, no off-target effects, and a dwarf phenotype. This improved prime-editing method can be efficiently applied to cell research and to generate mouse models.This study was supported by the Chung Yang, Cha Young Sun, & Jang Hi Joo Memorial Fund. This study was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) of Korea (Korea Mouse Phenotyping Project, NRF-2013M3A9D5072550, NRF-2020M3A9D5A01082439, NRF2019R1A2C2087198, and NRF- 2019M3A9H1103792)

Laboratory information management system for COVID-19 non-clinical efficacy trial data

Background : As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results : In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions : This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.This research was supported by the National research foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2020M3A9I2109027 and 2021M3H9A1030260)

Sparse Diffusion Least Mean-Square Algorithm with Hard Thresholding over Networks

This paper proposes a distributed estimation technique utilizing the diffusion least mean-square (LMS) algorithm, specifically designed for sparse systems in which many coefficients of the system are zeros. To efficiently utilize the sparse representation of the system and achieve a promising performance, we have incorporated L0-norm regularization into the diffusion LMS algorithm. This integration is accomplished by employing hard thresholding through a variable splitting method into the update equation. The efficacy of our approach is validated by comprehensive theoretical analysis, rigorously examining the mean stability as well as the transient and steady-state behaviors of the proposed algorithm. The proposed algorithm preserves the behavior of large coefficients and strongly enforces smaller coefficients toward zero through the relaxation of L0-norm regularization. Experimental results show that the proposed algorithm achieves superior convergence performance compared with conventional sparse algorithms

Dual Targeting of EGFR with PLK1 Exerts Therapeutic Synergism in Taxane-Resistant Lung Adenocarcinoma by Suppressing ABC Transporters

To overcome the limitations of chemoresistance, combination therapies using druggable targets have been investigated. Our previous studies led us to hypothesize that the downregulation of PLK1 expression or activity can be one strategy to overcome the hurdles of taxane resistance by the downregulation of ABC transporters. To explore this, various versions of PLK1 including a constitutively active version, kinase-dead form, and polo-box domain mutant were expressed in paclitaxel-resistant lung adenocarcinoma (LUADTXR). Targeting PLK1 using shRNA or non-functional mutants downregulated ABCB1, ABCC9, and ABCG2 in LUADTXR cells, which was similar to the downregulation effects from treatment with PLK1 inhibitors. The high expression of EGFR in LUAD led us to administer gefitinib, showing a markedly reduced EGFR level in LUADTXR cells. When gefitinib and PLK1 inhibitors were combined, LUADTXR cells tended to undergo apoptosis more effectively than parental cells, showing a synergistic effect on the downregulation of ABC transporters through c-Myc and AP-1. Clinical data provide evidence for the relevance between survival rates and expressions of PLK1 and EGFR in LUAD patients. Based on these results, we suggest that a combination of gefitinib and PLK1 inhibitors exerts strong synergism in LUADTXR, which helps to overcome the limitations associated with taxanes

The Validity of Two Neuromotor Assessments for Predicting Motor Performance at 12 Months in Preterm Infants

ObjectiveTo evaluate the validity of the Test of Infant Motor Performance (TIMP) and general movements (GMs) assessment for predicting Alberta Infant Motor Scale (AIMS) score at 12 months in preterm infants.MethodsA total of 44 preterm infants who underwent the GMs and TIMP at 1 month and 3 months of corrected age (CA) and whose motor performance was evaluated using AIMS at 12 months CA were included. GMs were judged as abnormal on basis of poor repertoire or cramped-synchronized movements at 1 month CA and abnormal or absent fidgety movement at 3 months CA. TIMP and AIMS scores were categorized as normal (average and low average and >5th percentile, respectively) or abnormal (below average and far below average or <5th percentile, respectively). Correlations between GMs and TIMP scores at 1 month and 3 months CA and the AIMS classification at 12 months CA were examined.ResultsThe TIMP score at 3 months CA and GMs at 1 month and 3 months CA were significantly correlated with the motor performance at 12 months CA. However, the TIMP score at 1 month CA did not correlate with the AIMS classification at 12 months CA. For infants with normal GMs at 3 months CA, the TIMP score at 3 months CA correlated significantly with the AIMS classification at 12 months CA.ConclusionOur findings suggest that neuromotor assessment using GMs and TIMP could be useful to identify preterm infants who are likely to benefit from intervention

High performance carbon nanotubes thin film transistors by selective ferric chloride doping

Single wall carbon nanotubes (SWNT) have been a significant research topic as active layers for thin film transistors (TFTs) due to their high charge carrier mobility beyond that of crystalline silicon. In this study, we report an effective approach to achieve a very high field-effect mobility and on/off ratio for solution processed semiconducting SWNT TFTs, by selective doping through contact with a thin ferric chloride (FeCl3) dopant layer. The semiconducting layer is formed by a double spin coating of the highly purified (>99%) high pressure carbon mono oxide (HiPCO) SWNT sorted by wrapping of poly (3-dodecylthiophene-2,5-diyl) (P3DDT). In order to achieve effective hole injection from the top Au source electrode without increasing the off-state drain current, less purified (98-99%) SWNTs produced by the plasma discharge process sorted by wrapping of poly (9,9-di-n-dodecylfluorene) (PFDD) are formed on the top of HiPCO film. Significantly improved TFT performance is achieved by the insertion of a few nanometers of a FeCl3 dopant layer at the semiconductor-contact interface. A significant high hole field-effect of 48.35 +/- 3.11 cm(2)V(-1)s(-1) (bare: 6.18 +/- 0.87 cm(2)V(-1)s(-1)) with a reasonable on/off current ratio of 10(5), and low off current of similar to 80 pA, are obtained by controlling the concentration of FeCl3 dopant (thickness = 1.5 nm) at the contact. Mobility is improved further at 2.5 nm thickness of the FeCl3 dopant layer resulting in a hole mobility of 177 +/- 13.2 cm(2) V(-1)s(-1), an on/off ratio of 7.4 x 10(3), and off state current of 1.2 x 10(-9) A.11Ysciescopuskc