BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, which is highly prone to bone marrow (BM) metastasis. BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB. METHODS: The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels. RESULTS: Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression. CONCLUSIONS: A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It's also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways.

Membrane fouling mechanisms in the presence of microplastics and organic matter: The unexpected mitigating role of Ca2.

Ultrafiltration (UF) is demonstrated to be highly effective in the removal of microplastics (MPs), but the presence of coexisting foulants introduces significant uncertainties into the associated membrane fouling behaviors. In this study, membrane fouling mechanisms were investigated when MPs, represented by polystyrene (PS), coexisted with typical organic foulants (sodium alginate, SA) and inorganic ions (Ca2+). Fouling tests revealed that the order of Ca2+ addition significantly impacted the fouling behavior of the SA-PS combined foulants. Specifically, the specific filtration resistance (SFR) was reduced by 40.82 % in the SA-PS-Ca2+ foulants and by 90.92 % in the SA-Ca2+-PS foulants, compared to the SA-PS foulants. X-ray photoelectron spectroscopy and density functional theory calculations indicated that sufficient cross-linking of Ca2+ with SA molecular chains in the SA-Ca2+-PS foulants, forming a large-scale 3D network that encapsulated more PS particles and resulted in larger flocs than those found in the SA-PS-Ca2+ foulants. According to extended Flory-Huggins theory, the improved filtration performance of the SA-PS combined foulants was due to substantial changes in chemical potential during their transition from gel to flocs upon Ca2+ addition. Furthermore, interfacial thermodynamic analyses suggested that increased repulsion between SA-Ca2+-PS foulants and between them and the membrane led to a looser fouling layer, significantly mitigating membrane fouling. This study elucidates the fouling mechanisms in the presence of MPs and other foulants from the perspectives of energy changes and molecular structures, providing novel insights for developing strategies to mitigate membrane fouling.

Impact of the COVID-19 pandemic on the demographic and disease burden of pediatric malignant solid tumors in China: a single-center, cross-sectional study.

Background: With the development of the novel coronavirus disease 2019 (COVID-19), China implemented measures in an attempt to control the infection rate. We conducted a single-center, cross-sectional study to ascertain the impact of the COVID-19 pandemic on the equitable availability of medical resources for children diagnosed with malignant solid tumors in China. Methods: Data on the demographics, clinical characteristics, and medical expenses of 876 patients diagnosed with neuroblastoma, rhabdomyosarcoma (RMS), Wilms tumor, hepatoblastoma (HB), Ewing sarcoma (ES), and central nervous system (CNS) tumors from 2019 to 2021, during the COVID-19 pandemic, were retrospectively collected from the National Center for Children's Health. The Pearson χ2 test and Mann-Whitney test were performed to analyze the differences among variables. Results: Except for the regional origin of children with tumors during the epidemic, no significant differences were found in the demographic or clinical characteristics of patients at initial diagnosis. The number of patients from northern China and northeastern China who attended Beijing Children's Hospital (BCH) increased after the outbreak of COVID-19 (P=0.001). There was no significant alteration observed in the frequency of hospitalizations per individual per annum (P=0.641) or the mean expense incurred per individual per hospitalization (P=0.361). In addition, the medical insurance coverage rate of real-time settlement increased year by year. Conclusions: After the COVID-19 outbreak, the origin of patients with solid tumor who visited BCH was concentrated in the northern region of China. COVID-19 had no impact on the other demographic factors, clinical characteristics, or economic burden of patients with pediatric malignant solid tumors.

Association of betatrophin amounts with 25-(OH)D levels in patients with gestational diabetes mellitus.

ABSTRACT: To determine the association of betatrophin amounts with 25-(OH)D levels in gestational diabetes mellitus (GDM) patients, and to provide new targets for the prevention and treatment of GDM.This study included 40 GDM patients (GDM group) and 37 healthy pregnant women (control group). Betatrophin, 25-(OH)D, fasting blood glucose (FBG), HbA1c, hsCRP, and FINS levels in peripheral blood, as well as betatrophin and 25-(OH)D amounts in cord blood, were measured. Then, associations of betatrophin levels with 25-(OH)D amounts and other indexes were determined.Maternal (P = .011) and cord (P = .022) blood betatrophin levels were significantly lower in the GDM group compared with control group. Cord blood betatrophin levels were higher compared with maternal blood amounts in both the GDM and control groups (both P = .000). Serum betatrophin levels were positively associated with 25-(OH)D levels (r = 0.677, P = .000), but negatively associated with hsCRP (r = -0.335, P = .037) and HOMA-IR (r = -0.346, P = .031) levels in the GDM group. Fetal weight was higher in the GDM group compared with control group (P = .023), and negatively associated with cord blood betatrophin amounts in the GDM group (r = -0.342, P = .031). However, cord blood betatrophin levels were not significantly associated with body length, Apgar score, and cord blood 25-(OH)D levels in the GDM group (all P > .05).Serum betatrophin and 25-(OH) D levels were positively associated in women with GDM, and both significantly lower compared with control values. Fetal weight was higher in the GDM group and associated with cord blood betatrophin. These findings provide insights into developing new predictive biomarkers or therapeutic targets for GDM.

Influences of HIF-lα on Bax/Bcl-2 and VEGF expressions in rats with spinal cord injury.

Hypoxia-inducible factor 1-alpha (HIF-1α) is a subunit of HIF-l and thought to be able to protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. This study aimed to investigated whether recombinant adenovirus vector over-expressing HIF-lα could affect apoptosis-related proteins (Bcl-2 and Bax) and vascular endothelial growth factor (VEGF) in a rat spinal cord injury (SCI) model. A total of 60 male SD rats were divided into 4 groups: Sham, Control, Ad-Blank and Ad-HIF-1α groups. 1, 3, 7, 14, 28 days after surgery, the behavioral recovery was evaluated with BBB scales. Then, rats were sacrificed and the spinal cord was collected for detection of Bcl-2, Bax and VEGF expressions by immunohistochemistry. Results showed the Bcl-2, Bax, VEGF and HIF-lα expressions increased in animals with SCI, but the increase in Bcl-2, VEGF and HIF-lα expressions were higher in Ad-HIF-1α group when compared with other groups, but Bax expression decreased significantly. In addition, administration of Ad-HIF-1α significantly reduced apoptotic cells and promoted the recovery of neurological function. In conclusion, administration of Ad-HIF-1α after SCI could ameliorate neuronal apoptosis and promote angiogenesis in rats. Our study provides a basis for further exploration of the relationship between HIF1α and SCI.