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[Objective] To detect the gene mutations in three children with neurofibromatosis type1 (NF1), and explore the new pathogenic mutations and phenotypes of NF1. [Methods] Exome sequencing and targeted gene panels were performed in the probands to determine the mutation sites. After detecting suspected mutation types in the patients, the mutation sites were verified in all patients and their parents by high-throughput sequencing and Sanger sequencing techniques. [Results] After birth, all three children (two males and one female) presented with multiple cafe-au-lait spots, axillary or inguinal freckles, and one with neurofibromas. All three patients were diagnosed with NF1, and were with a identified mutation site in the NF1 gene, i.e., c.3921delT, c.5206-2A>C and c.893T>G, respectively. The c.3921delT and c.893T>G have not been reported previously. The NF1 variation in one patient was inherited from the father, and the other two were spontaneous mutation. [Conclusion] We identify two novel mutations in NF1 gene in three children with NF1, expanding the pathogenic mutation sites of the NF1 gene.

Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality. Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders, which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries. Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases. In this review, we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations, epidemiology, and aberrant cellular composition involving the biliary ductules, cholangiocytes, immune system, fibroblasts, and the microbiome. We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies. This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.

Background: Pseudomonas aeruginosa (P. aeruginosa) is a type of pathogen that takes advantage of opportunities to infect and form biofilm during infection. Inhibiting biofilm formation is a promising approach for the treatment of biofilm-related infections. Methods: Here, Y0-C10-HSL (N-cyclopentyl-n-decanamide) was designed, synthesized, and tested for its effect on biofilm formation, motility, and the Caenorhabditis elegans (C. elegans) survival assay. In addition, the molecular mechanism of Y0-C10-HSL on P. aeruginosa biofilm formation was explored using transcriptome analysis. Results: At a concentration of 200 μmol/L Y0-C10-HSL, biofilm and exopolysaccharides were decreased by 38.5% and 29.3%, respectively; Y0-C10-HSL effectively dispersed the pre-formed biofilm and inhibited the motility ability of P. aeruginosa; and the C. elegans survival assay showed that Y0-C10-HSL was safe and provided protection to C. elegans against P. aeruginosa infection (the survival rates of C. elegans were higher than 74% and increased by 39%, 35.1%, and 47.5%, respectively, when treated with 200 μmol/L Y0-C10-HSL at 24, 48, and 80 h). Transcriptome analysis showed that 585 differentially expressed genes (DEGs) were found after treatment with 200 μmol/L Y0-C10-HSL, including 254 up-regulated DEGs and 331 down-regulated DEGs. The genes involved in the quorum sensing system and biofilm formation were down-regulated. Conclusions: Y0-C10-HSL inhibited the biofilm formation and dispersed the pre-formed biofilm of P. aeruginosa through down-regulated genes related to quorum sensing pathways and biofilm formation. These findings provide a theoretical foundation for the treatment and prevention of antibiotic resistance in clinical and environmental microorganisms such as P. aeruginosa. [ABSTRACT FROM AUTHOR]

This study aimed to explore the combined effects of serum vitamin-D level and tobacco exposure on the risk of overweight and obesity in children. This cross-sectional study analysed the data of 11 636 children aged 2–17 years from the National Health and Nutrition Examination Surveys database between 2007 and 2018. Univariable and multivariate weighted logistic regression models were used to analyse the associations of serum vitamin-D or cotinine levels with overweight and obesity in children as well as the combined effects of serum vitamin-D and cotinine on the risk of overweight and obesity in children. Subgroup analysis was performed in terms of gender, age, race and household smokers. OR with corresponding 95 % CI was presented. The elevated risk of overweight and obesity in children was found in those with serum vitamin-D < 20 ng/ml (OR = 1·44, 95 % CI: 1·29, 1·61). Also, the odds of overweight and obesity in children was 1·14 (OR = 1·14, 95 % CI: 1·01, 1·29) in children with cotinine ≥ 0·05 ng/ml. Relative to participants with serum vitamin-D ≥ 20 ng/ml and cotinine < 0·05 ng/ml, increased risk of overweight and obesity was identified in those with serum vitamin-D < 20 ng/ml and cotinine < 0·05 ng/ml (OR = 1·45, 95 % CI: 1·26, 1·68) and serum vitamin-D < 20 ng/ml and cotinine ≥ 0·05 ng/ml (OR = 1·62, 95 % CI: 1·38, 1·91). Serum vitamin-D and cotinine exposure had combined effects on the risk of overweight and obesity in children. [ABSTRACT FROM AUTHOR]

Highlights With the rapid development of electric vehicles, a hybrid composite structure has been designed for the battery pack bottom guard to enhance impact resistance and reduce weight. The glass fiber‐reinforced polypropylene (GFPP)/DP980 honeycomb sandwich structure consists of GFPP panels with a polypropylene honeycomb core. DP980 advanced high‐strength steel plate is encapsulated within the structure, inspired by fiber metal laminates. A lightweight and high‐strength sandwich composite lay‐up solution was determined through equivalent bending stiffness theory, finite element simulation and experiment. An asymmetric sandwich structure with the steel plate on the impacted side enhanced flexural strength and ductility, demonstrating different failure sequences and a higher bending strength of 77.64 MPa compared to 50.18 MPa when the steel plate was on the unimpacted side. As impact energy increased from 100 to 200 J, the sandwich structure showed higher peak impact load, deeper craters, and increased bulge height, with significant delamination up to 175 J, while gravel impact tests revealed minimal flexural strength reduction (4.92%) even after repeated impacts. This study confirms that the use of thermoplastic sandwich structures is a viable and promising option for crash safety and the lightweight design of battery pack bottom guards. The thermoplastic honeycomb sandwich structure is polypropylene‐based. The use of advanced high strength steel is inspired by fiber metal laminates. Both thickness and surface density are considered in the structural design. The steel plate placed on the impacted side improves the flexural behavior. The sandwich structure has excellent impact resistance and lightweight level. [ABSTRACT FROM AUTHOR]