SUMMARY Here, we report the clinical observations of two Chinese fraternal twins who presented with severe dehydration, poor feeding, and absence of stimuli responses within a few days of birth. Trio clinical exome sequencing of the family identified compound heterozygous intronic variants (c.1439+1G>C and c.875+1G>A) in SCNN1A gene in these two patients. Sanger sequencing results showed that the c.1439+1G>C variant was inherited from the mother, and c.875+1G>A from the father, rarely reported in pseudohypoaldosteronism type 1 with sodium epithelial channel destruction (PHA1b) patients. Case 2 received timely symptomatic treatment and management after obtaining these results, which improved the clinical crisis. Our results suggest that the compound heterozygous splicing variants in SCNN1A were responsible for PHA1b in these Chinese fraternal twins. This finding extends the knowledge of the variant spectrum in PHA1b patients and highlights the application of exome sequencing in critically ill newborns. Finally, we discuss supportive case management, particularly in maintaining blood potassium concentration.

RESUMO O uso de engenharia assistida por computador (CAE) na fase de projeto do conceito do automóvel tornou-se um ponto de acesso na pesquisa de fatores humanos. Com base no software computacional biomecânico musculoesquelético humano, foi construído um modelo musculoesquelético sentado para descrever a postura sentada natural de um condutor. A interação entre um motorista e um carro em várias combinações de ângulos de inclinação do assento-pan/encosto foi analisada usando uma abordagem dinâmica do verso. A fim de descobrir a postura de condução “mais confortável” do assento-pan/encosto, o efeito dos ângulos de inclinação do assento-pan/dorso sobre o grau de atividade muscular e a força de compressão intradiscal L4-L5 foi investigado. Os resultados mostraram que um ângulo de inclinação para trás muito maior, aproximadamente 15°, e um ligeiro assento-pan para trás, cerca de 7°, pode aliviar a fadiga muscular e levar a dirigir em uma posição confortável. Posteriormente, de acordo com as conclusões acima expostas, foi construída uma função preliminar de conforto ao dirigir.

SUMMARY Using computer-aided engineering (CAE) in the concept design stage of automobiles has become a hotspot in human factor engineering research. Based on human musculoskeletal biomechanical computational software, a seated human-body musculoskeletal model was built to describe the natural sitting posture of a driver. The interaction between the driver and car in various combinations of seat-pan/back-rest inclination angles was analyzed using an inverse-dynamics approach. In order to find out the “most comfortable” driving posture of the seat-pan/back-rest, the effect of seat-pan/back-rest inclination angles on the muscle activity degree, and the intradiscal L4-L5 compression force were investigated. The results showed that a much larger back-rest inclination angle, approximately 15°, and a slight backward seat-pan, about 7°, may relieve muscle fatigue and provide more comfort while driving. Subsequently, according to the findings above, a preliminary driving-comfort function was constructed.

RESUMO OBJETIVO O glioblastoma (GBM) é um câncer comum e de alta mortalidade. A transição epitélio-mesênquima (EMT) desempenha um papel vital no desenvolvimento do glioblastoma. O objetivo deste estudo é avaliar o papel do miR-125a-5p no glioblastoma e a tumorigênese de células-troco cancerígenas resistentes a medicamentos quimioterápicos em gliomas cerebrais. METODOLOGIA Os papéis do miR-125a-5p na regulação de células-tronco cancerígenas, EMT, migração e invasão do glioblastoma foram medidos neste estudo. RESULTADOS Mostramos a função do miR-125a-5p na regulação das células-tronco cancerígenas, EMT, migração e invasão do glioblastoma. O miR-125a-5p pode inibir o fenótipo e a EMT de células-tronco cancerígenas em células de glioblastoma. Além disso, a sua superexpressão pode regular de forma significante genes associados às células-tronco cancerígenas e a expressão de genes associados à EMT em células de glioblastoma. CONCLUSÕES Concluímos que o miR-125a-5p é um dos principais microRNAs na regulação de células-tronco cancerígenas e programas de EMT em glioblastomas, e os resultados sugerem que o miR-125a-5p pode ser um novo alvo terapêutico em casos de glioblastoma.

SUMMARY OBJECTIVE Glioblastoma (GBM) is a common type of cancer with high mortality. Epithelial to mesenchymal transition (EMT) plays a vital role in the development of glioblastoma. The aim of this study is to evaluate the role of miR-125a-5p in glioblastoma and in the tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma. METHODS The role of miR-125a-5p in the regulation of CSCs, EMT, migration, and invasion in glioblastoma was measured in this study. RESULTS We showed the roles of miR-125a-5p in the regulation of CSCs, EMT, migration, and invasion in glioblastoma. miR-125a-5p can inhibit the CSCs phenotype and EMT in glioblastoma cells. In addition, its over-expression can significantly regulate CSCs-associated genes and EMT-associated gene expression in glioblastoma cells. CONCLUSIONS We concluded that miR-125a-5p is one of the key microRNAs regulating CSCs and EMT programs in glioblastoma. The results suggested that miR-125a-5p might be a novel therapy target for glioblastoma.

This study aimed to investigate how 6-bromoindirubin-3’-oxime (BIO) increases the osteogenic differentiation of canine bone mesenchymal stem cells (BMSCs) and the role of the Wnt/β-catenin signaling pathway in this process. We mimicked the effect of Wnt by adding BIO to the culture medium of BMSCs and examined whether canonical Wnt signaling positively affects the differentiation of these cells into osteoblasts. Canine BMSCs were cultured with 0.5 and 1.0 μM BIO under osteogenic conditions and then differentiation markers were investigated. It was found that BIO significantly increased the activity of alkaline phosphatase (ALP), the number of ALP-positive cells, the mineralization level and calcium deposits. Moreover, cells cultured with 0.5 and 1.0 μM BIO exhibited detectable β-catenin expression in their nuclei, and showed upregulated β-catenin and glycogen synthase kinase 3 beta(GSK3β) phosphorylation compared to untreated cells. In addition, BIO enhanced the mRNA expression of osteoblast differentiation markers such as ALP, runt-related transcription factor 2, collagen I, osteocalcin, and osteonectin. In conclusion, BIO upregulated GSK3β phosphorylation and inhibited its activity, thereby activating the Wnt/β-catenin signaling pathway and promoting the osteogenic differentiation of canine BMSCs. The effect of 1.0 μM BIO on BMSCs differentiation was stronger than that of 0.5 μM BIO.

Background: Enzymatic decolourization has been recently proposed as a promising and eco-friendly method for treatment of synthetic dye-contaminated wastewaters. However, the processes require large quantities of enzymes, attracting significant attention in developing efficient methods for mass production of multifunctional enzymes. Several methods such as response surface methodology (RSM) and orthogonal experiment have been applied to optimize the parameters in bioprocesses for enzyme production. Results: In the present study, a laccase-like enzyme, phenoxazinone synthase (PHS) originated from Streptomyces antibioticus was recombinantly expressed in Escherichia coli BL21 (DE3). The production of PHS in E. coli BL21 was optimized by response surface methodology based on Box-Behnken design. A full third-order polynomial model was generated by data analysis with Statistica 8.0 in which the optimal conditions for PHS production were calculated to be 1.525 mM CuSO4 and 16.096 hrs induction at temperature of 29.88ºC. The highest PHS production under optimal conditions was calculated to be 4098.51 U/l using the established model. Average PHS production obtained from actual production processes carried out under the calculated optimal conditions was 4052.00 U/l, very close to the value predicted by the model. Crude PHS was subsequently tested in Congo red decolourization which exhibited a low decolourization rate of 27% without mediator. Several mediators were found to improve PHS-catalyzed Congo red decolourization, with the highest rate of 73.89% obtained with 2,2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) as mediator under optimized conditions of 4000 U/l PHS activity, 10 μM ABTS, 100 μM Congo red, and 8 hrs reaction time. Conclusion: Our results indicated that PHS recombinantly produced in E. coli BL21 was a prospective enzyme for decolorizing reactive dye Congo red.