Effects of enhanced starch-xanthan gum synergism on their physicochemical properties, functionalities, structural characteristics, and digestibility.

The limited and unstable interactions between potato starch (PS) and xanthan gum (XG) by simple mixing (SM) lead it difficult to induce substantial changes in starchy products. Structural unwinding and rearrangement of PS and XG by critical melting and freeze-thawing (CMFT) were used to promote PS/XG synergism, and the physicochemical, functionalities, and structural properties were investigated. Compared to "Native" and SM, CMFT promoted the formation of large clusters with a rough granular surface and wrapped by a matrix composed of released soluble starches and XG (SEM), thus making the composite more compact to thermal processes, such as the significantly decreased WSI and SP, and increased the melting temperatures. The enhanced synergism of PS/XG after CMFT effectively decreased the breakdown viscosity from ~3600 (Native) to ~300 mPa·s and increased the final viscosity from ~2800 (Native) to ~4800. CMFT significantly increased the functional properties of PS/XG composite, including water/oil absorptions and resistant starch content. CMFT caused the partial melting and loss of large packaged structures in starch (XRD, FTIR, and NMR), and the melting and the loss of crystalline structure controlled at approximately 20 % and 30 %, respectively, are the most effective for promoting PS/XG interaction.

Simultaneous quantification of fat-soluble vitamins A, 25-hydroxylvitamin D and vitamin E in plasma from children using liquid chromatography coupled to Orbitrap mass spectrometry.

The fat-soluble vitamins A, D, E and K are micronutrients essential for physiological activity, metabolism and growth. Accurate and sensitive analytical methods are needed to support growing research into fat-soluble vitamins and their impact on children's growth and health. Here we report the first method for simultaneous quantification of fat-soluble vitamins A (retinol), 25-hydroxylvitamin D2, 25-hydroxylvitamin D3, and vitamin E (α-tocopherol) using a Q-Exactive Orbitrap mass spectrometer in high-resolution, parallel reaction monitoring mode. This method can select desired ions with high efficiency, potentially making it superior to triple-quadrupole mass spectrometers that employ multiple reaction monitoring. The proposed method offers excellent accuracy, specificity, and sensitivity, as demonstrated with plasma samples from healthy children.

Improving quality management of newborn screening in southwest China.

OBJECTIVE: Newborn screening (NBS) programs benefit tens of millions of infants worldwide each year. However, the extremely large screening populations and number of laboratories involved pose great challenges to maintaining high screening quality. To achieve continuous quality improvement, we established a comprehensive quality management system (CQMS) in southwest China. METHODS: External quality assessment (EQA) and internal quality control were carried out for basic quality management. We used 16 quality indicators (QIs) to monitor the entire screening process, with external supervision from the China National Accreditation Service for Conformity Assessment. All retrospective data for quality assessment were collected consecutively from laboratory management and patient follow-up systems. RESULTS: From 2015 to 2019, satisfactory EQA performance was achieved, with an average score greater than 97 for each screening item. QI monitoring showed that NBS quality improved continuously. The rate of health education provision increased from 90.9% to 100% and the recall rate after a positive primary screening increased from 85.4% to 99.2%. The unsatisfactory specimen rate and rate of newborns lost to follow-up decreased to 0.38% and 0.08%, respectively. CONCLUSIONS: Implementing a CQMS and monitoring the whole screening process using QIs may yield continuous quality improvement of NBS.

ARRB1-Promoted NOTCH1 Degradation Is Suppressed by OncomiR miR-223 in T-cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a type of aggressive leukemia with inferior prognosis. Although activating mutations of NOTCH1 are observed in most T-ALL cases, these mutations alone are not sufficient to drive the full development of T-ALL. ß-Arrestins (ARRB) are versatile and multifunctional adapter proteins that regulate diverse cellular functions, including promoting the development of cancer. However, the role of ARRBs in T-ALL has largely remained elusive. In this study, we showed that ARRB1 is expressed at low levels in assayed T-ALL clinical samples and cell lines. Exogenous ARRB1 expression inhibited T-ALL proliferation and improved the survival of T-ALL xenograft animals. ARRB1 facilitated NOTCH1 ubiquitination and degradation through interactions with NOTCH1 and DTX1. Mechanistically, the oncogenic miRNA (oncomiR) miR-223 targets the 3'-UTR of ARRB1 (BUTR) and inhibits its expression in T-ALL. Furthermore, overexpression of the ARRB1-derived miR-223 sponge suppressed T-ALL cell proliferation and induced apoptosis. Collectively, these results demonstrate that ARRB1 acts as a tumor suppressor in T-ALL by promoting NOTCH1 degradation, which is inhibited by elevated miR-223, suggesting that ARRB1 may serve as a valid drug target in the development of novel T-ALL therapeutics.Significance: These findings highlight a novel tumor suppressive function of the adaptor protein ß-arrestin1 in T-ALL.

Severe clinical manifestation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency associated with two novel mutations: a case report.

BACKGROUND: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is an autosomal recessive inborn error of metabolism, which will give rise to failure of ketogenesis in liver during illness or fasting. It is a very rare disease with only a few patients reported worldwide, most of which had a good prognosis after proper therapies. CASE PRESENTATION: We report a 9-month-old boy with mHS deficiency presenting with unusually severe and persistent acidosis after diarrhea and reduced oral food intake. The metabolic acidosis persisted even after supplementation with sugar and alkaline solution. Blood purification and assisted respiration alleviated symptoms, but a second onset induced by respiratory infection several days later led to multiple organ failure and death. Urine organic acid analysis during the acute episode revealed a complex pattern of ketogenic dicarboxylic and 3-hydroxydicarboxylic aciduria with prominent elevation of glutaric acid and adipic acid, which seem to be specific to mHS deficiency. Plasma acylcarnitine analysis revealed elevated 3-hydroxybutyrylcarnitine and acetylcarnitine. This is the first report of elevated 3-hydroxybutyrylcarnitine in mHS deficiency. Whole exome sequencing revealed a novel compound heterozygous mutation in HMGCS2 (c.100C > T and c.1465delA). CONCLUSION: This severe case suggests the need for patients with mHS deficiency to avoid recurrent illness because it can induce severe metabolic crisis, possibly leading to death. Such patients may also require special treatment, such as blood purification. Urine organic acid profile during the acute episode may give a hint to the disease.

Determination of optimal cutoff value to accurately identify glucose-6-phosphate dehydrogenase-deficient heterozygous female neonates.

BACKGROUND: Conventional screening tests to assess G6PD deficiency use a low cutoff value of 2.10 U/gHb which may not be adequate for detecting females with heterozygous deficiency. The aim of present study was to determine an appropriate cutoff value with increased sensitivity in identifying G6PD-deficient heterozygous females. METHODS: G6PD activity analysis was performed on 51,747 neonates using semi-quantitative fluorescent spot test. Neonates suspected with G6PD deficiency were further analyzed using quantitatively enzymatic assay and for common G6PD mutations. The cutoff values of G6PD activity were estimated using the receiver operating characteristic curve. RESULTS: Our results demonstrated that using 2.10 U/g Hb as a cutoff, the sensitivity of the assay to detect female neonates with G6PD heterozygous deficiency was 83.3%, as compared with 97.6% using 2.55 U/g Hb as a cutoff. The high cutoff identified 21% (8/38) of the female neonates with partial G6PD deficiency which were not detected with 2.10 U/g Hb. Our study found that high cutoffs, 2.35 and 2.55 U/g Hb, would increase assay's sensitivity to identify male and female G6PD deficiency neonates, respectively. CONCLUSIONS: We established a reliable cutoff value of G6PD activity with increased sensitivity in identifying female newborns with partial G6PD deficiency.