Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia

Introduction: Thalassemia could interfere with some assays for haemoglobin A1c (HbA1c) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA1c. We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA1c programme to simultaneously measure HbA1c and screen for thalassemia. Materials and methods: Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA1c programme (Sebia, France). For method comparison, HbA1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA1c from eight thalassaemia patients was confirmed by IFCC reference method. Results: Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA1c result in three samples with HbH due to the overlapping of HbBart’s with HbA1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Conclusions: Our results demonstrated the Capillarys 2FP HbA1c system could report an accurate HbA1c value in thalassemia silent/trait, and HbA2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart’s for HbH disease, HbF for β-thalassemia) may provide valuable information for screening

Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

© 2018 The Author(s). Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αvβ6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

GnRH agonist treatment for idiopathic central precocious puberty can improve final adult height in Chinese girls

Object To study the outcomes of GnRHa on final adult height in Chinese idiopathic central precocious puberty (ICPP) girls and the involved factor(s) that can predict height gain. Methods: We conducted a retrospective analysis on 10 years of data obtained from three clinical hospitals from January 2005 to March 2015, and 101 girls with ICPP, who received GnRHa therapy for more than six months and already reached their adult height were enrolled. Results: Height, bone age, midparent height, HtSDS, sexual development, therapy duration and predicted adult height(PAH)at start and end of GnRHa, and the final adult height(FAH) were recorded and calculated. Their PAH significantly increased at end of GnRHa (158.4±6.00cm), compared to that at the start of GnRHa(153.1±5.37cm) (P0.05). After GnRHa therapy, most of the ICPP girls reached their midparent height compared to that at start of GnRHa(P0.05). The percentage of adult short stature decreased and those reached midparent height significantly increased after GnRHa therapy, compared to that at start of GnRHa(60.6% vs.30.4% and 67.85% vs. 94.64%, respectively, P<0.05). Conclusions: GnRHa therapy to ICPP girls can effectively achieve the final adult height. After GnRHa therapy, most of these patients reached their midparent height, while few of these patients had an adult short stature

A 2D image 3D reconstruction function adaptive denoising algorithm

To address the issue of image denoising algorithms blurring image details during the denoising process, we propose an adaptive denoising algorithm for the 3D reconstruction of 2D images. This algorithm takes into account the inherent visual characteristics of human eyes and divides the image into regions based on the entropy value of each region. The background region is subject to threshold denoising, while the target region undergoes processing using an adversarial generative network. This network effectively handles 2D target images with noise and generates a 3D model of the target. The proposed algorithm aims to enhance the noise immunity of 2D images during the 3D reconstruction process and ensure that the constructed 3D target model better preserves the original image’s detailed information. Through experimental testing on 2D images and real pedestrian videos contaminated with noise, our algorithm demonstrates stable preservation of image details. The reconstruction effect is evaluated in terms of noise reduction and the fidelity of the 3D model to the original target. The results show an average noise reduction exceeding 95% while effectively retaining most of the target’s feature information in the original image. In summary, our proposed adaptive denoising algorithm improves the 3D reconstruction process by preserving image details that are often compromised by conventional denoising techniques. This has significant implications for enhancing image quality and maintaining target information fidelity in 3D models, providing a promising approach for addressing the challenges associated with noise reduction in 2D images during 3D reconstruction

The Application of Crystallization Kinetics in Optimizing Morphology of Active Layer in Non-Fullerene Solar Cells

Organic photovoltaics (OPVs) have attracted widespread attention and became an important member of clean energy. Recently, their power conversion efficiency (PCE) has surpassed 19%. As is well known, the morphology of the active layer in OPVs crucially influences the PCE. In consideration of the intricate interactions between the donor molecules and acceptor molecules, the precise control of the morphology of the active layer is extremely challenging. Hence, it is urgent to develop effective methods to fabricate the hierarchical structure of the active layer. One significant driving force for the morphological evolution of the active layer is crystallization. Therefore, regulating the crystallization kinetics is an effective strategy for morphology control. In this review, we present the kinetic strategies recently developed to highlight their significance and effectiveness in morphology control. By applying these kinetic strategies, the hierarchical structure, including phase separation, domain size, crystallinity, and molecular orientation of the active layer can be optimized in different blend systems, leading to an improved PCE of OPVs. The outcomes set the stage for future advancements in device performance

A comparative evaluation of the analytical performances of Capillarys 2 Flex Piercing, Tosoh HLC-723 G8, Premier Hb9210, and Roche Cobas c501 Tina-quant Gen 2 analyzers for HbA1c determination

Introduction: Haemoglobin A1c (HbA1c) is widely used in the management of diabetes. Therefore, the reliability and comparability among different analytical methods for its detection have become very important. Materials and methods: A comparative evaluation of the analytical performances (precision, linearity, accuracy, method comparison, and interferences including bilirubin, triglyceride, cholesterol, labile HbA1c (LA1c), vitamin C, aspirin, fetal haemoglobin (HbF), and haemoglobin E (Hb E)) were performed on Capillarys 2 Flex Piercing (Capillarys 2FP) (Sebia, France), Tosoh HLC-723 G8 (Tosoh G8) (Tosoh, Japan), Premier Hb9210 (Trinity Biotech, Ireland) and Roche Cobas c501 (Roche c501) (Roche Diagnostics, Germany). Results: A good precision was shown at both low and high HbA1c levels on all four systems, with all individual CVs below 2% (IFCC units) or 1.5% (NGSP units). Linearity analysis for each analyzer had achieved a good correlation coefficient (R2 > 0.99) over the entire range tested. The analytical bias of the four systems against the IFCC targets was less than ± 6% (NGSP units), indicating a good accuracy. Method comparison showed a great correlation and agreement between methods. Very high levels of triglycerides and cholesterol (? 15.28 and ? 8.72 mmol/L, respectively) led to falsely low HbA1c concentrations on Roche c501. Elevated HbF induced false HbA1c detection on Capillarys 2FP (> 10%), Tosoh G8 (> 30%), Premier Hb9210 (> 15%), and Roche c501 (> 5%). On Tosoh G8, HbE induced an extra peak on chromatogram, and significantly lower results were reported. Conclusions: The four HbA1c methods commonly used with commercial analyzers showed a good reliability and comparability, although some interference may falsely alter the result

DataSheet_1_Nudix hydrolase 14 influences plant development and grain chalkiness in rice.docx

Nudix hydrolases (NUDX) can hydrolyze a wide range of organic pyrophosphates and are widely distributed in various organisms. Previous studies have shown that NUDXs are extensively involved in biotic and abiotic stress responses in different plant species; however, the role of NUDXs in plant growth and development remains largely unknown. In the present study, we identified and characterized OsNUDX14 localized in the mitochondria in rice. Results showed that OsNUDX14 is constitutively expressed in various tissues and most strongly expressed in mature leaves. We used CRISPR/Cas9 introducing mutations that editing OsNUDX14 and its encoding product. OsNUDX14-Cas9 (nudx14) lines presented early flowering and a larger flag leaf angle during the reproductive stage. In addition, OsNUDX14 affected grain chalkiness in rice. Furthermore, transcript profile analysis indicated that OsNUDX14 is associated with lignin biosynthesis in rice. Six major haplotypes were identified by six OsNUDX14 missense mutations, including Hap_1 to Hap_6. Accessions having the Hap_5 allele were geographically located mainly in South and Southeast Asia with a low frequency in the Xian/indica subspecies. This study revealed that OsNUDX14 is associated with plant development and grain chalkiness, providing a potential opportunity to optimize plant architecture and quality for crop breeding.</p