Nephrotic syndrome in a child with neurofibromatosis type 1: A case report and literature review.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that caused by NF1 mutations. NF1 gene encodes neurofibromin (a GTPase-activating protein) and plays a regulatory role in many signalling pathway such as the Ras/MAPK pathway, which is important for regulating cell growth, proliferation and neural development. Therefore, NF1 gene mutations causes the excessive activation of signalling pathways and uncontrolled cell growth. NF1 exhibits complete genetic penetrance and clinical heterogeneity. Glomerular disease has rarely been reported in patients with NF1, especially in children. Currently, the relationship between NF1 and nephrotic syndrome is unclear. Here, we present a case of NF1 with nephrotic syndrome and further explore the association between NF1 and glomerular diseases. It also reminds clinicians that NF1 has complex and highly variable clinical manifestations and that a comprehensive workup is essential for patients.

Impact of cell wall polysaccharide modifications on the performance of Pichia pastoris: novel mutants with enhanced fitness and functionality for bioproduction applications.

BACKGROUND: Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities. RESULTS: Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in ß-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage. CONCLUSIONS: Two novel P. pastoris chassis hosts with impaired ß-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.

Extramedullary relapsed acute lymphoblastic leukemia presenting as asymptomatic acute kidney injury after hematopoietic stem cell transplantation.

Acute kidney injury (AKI) is a common complication in children with hematological malignancies. Although AKI due to infiltration of tumor cells in children is rare, it negatively impacts treatment outcomes and increases the risk of mortality. We introduce a case of a child with acute lymphoblastic leukemia (ALL) who experienced kidney relapse resulting in asymptomatic AKI after remission from treatment, to remind clinicians not to overlook the primary disease in clinical judgment. In cases of unexplained AKI, kidney biopsy should be performed when feasible to get an accurate diagnosis and scientific treatment. In brief, children with leukemia who have achieved remission after treatment still need regular monitoring of urine routine and kidney function.

JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis.

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiology and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of molecular biology and immunological techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theoretical basis for understanding the pathogenesis and potential therapeutic targets of UC.