Background: A hallmark of acute promyelocytic leukemia (APL) is the expression of PML/RARα fusion protein. Treatment with all-trans retinoic acid (ATRA) results in the terminal differentiation of neutrophil granulocytes. However, the underlying mechanisms remain largely unknown. Here, we identify and elucidate a novel differentiation-suppressive model of APL involving the histone demethylase KDM3B, which has been identified as a suppressor of the tumor genes involved in hematopoietic malignancies. Methods: First, we established a KDM3B knockdown NB4 cell model to determine the functional characteristics of KDM3B by cell proliferation assay and flow cytometry. Then, we performed ChIP-seq and ATAC-seq to search for potential relationships among KDM3B, histone modification (H3K9me1/me2) and the chromatin state. Finally, molecular biological techniques and a multi-omics analysis were used to explore the role of KDM3B in differentiation of the leukemia cells after ATRA treatment. Results: We found that knocking down KDM3B contributed to the growth of NB4 APL cells via the promotion of cell-cycle progression and blocked granulocytic differentiation. Through global and molecular approaches, we provided futher evidence that knocking down KDM3B altered the global distribution of H3K9me1/me2 and increased the chromatin accessibility. Moreover, knocking down KDM3B inhibited the ATRA-induced degradation of the PML/RARα oncoprotein. Conclusion: Our study suggested that KDM3B was able to inhibit APL progression by maintaining chromatin in a compact state and facilitating the ATRA-mediated degradation of PML/RARα. Taken together, the results show that KDM3B may be an alternative target for the treatment regimens and the targeted therapy for APL by sustaining the function of PML/RARα fusion protein.

Fluoride has strong electronegativity and exposes diversely in nature. Water fluoridation is the most pervasive form of occurrence, representing a significant threat to human health. In this study, we investigate the morphometric and physiological alterations triggered by fluoride stimulation during the embryogenesis of zebrafish and reveal its putative effects of stage- and/or dose-dependent. Fluoride exhibits potent biological activity and can be extensively absorbed by the yolk sac, exerting significant effects on the development of multiple organs. This is primarily manifested as restricted nutrient utilization and elevated levels of lipid peroxidation, further leading to the accumulation of superoxide in the yolk sac, liver, and intestines. Moreover, pericardial edema exerts pressure on the brain and eye development, resulting in spinal curvature and reduced body length. Besides, acute fluoride exposure with varying concentrations has led to diverse teratogenic outcomes. A low dose of water fluoridation tends to induce abnormal development of the embryonic yolk sac, while vascular malformation is widely observed in all fluoride-treated groups. The effect of fluoride exposure on blood circulation is universally present, even in zebrafish larvae that do not exhibit obvious deformities. Their swimming behavior is also affected by water fluoridation, resulting in reduced activity and delayed reactions. In conclusion, this study provides valuable insights into the monitoring of environmental quality related to water fluoridation and disease prevention.

Background: Streptococcus agalactiae or group B Streptococcus (GBS) is a leading infectious cause of neonatal morbidity and mortality. It is essential to establish a robust method for the rapid and ultra-sensitive detection of GBS in pregnant women with premature rupture of membrane (PROM). Methods: This study developed a CRISPR-GBS assay that combined the advantages of the recombinase polymerase amplification (RPA) and CRISPR/Cas12a system for GBS detection. The clinical performance of the CRISPR-GBS assay was assessed using vaginal or cervical swabs that were collected from 179 pregnant women with PROM, compared in parallel to culture-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry (culture-MS) method and real-time quantitative polymerase chain reaction (qPCR) assay. Results: The CRISPR-GBS assay can be completed within 35 min and the limit of detection was as low as 5 copies μL⁻¹. Compared with the culture-MS, the CRISPR-GBS assay demonstrated a sensitivity of 96.64% (144/149, 95% confidence interval [CI] 92.39–98.56%) and a specificity of 100% (30/30, 95% CI 88.65–100%). It also had a high concordance rate of 98.88% with the qPCR assay. Conclusions: The established CRISPR-GBS platform can detect GBS in a rapid, accurate, easy-to-operate, and cost-efficient manner. It offered a promising tool for the intrapartum screening of GBS colonization.

Schiff bases have remarkable anticancer activity and are used for glioma therapy. However, the poor water solubility/dispersibility limits their therapeutic potential in biological systems. To address this issue, carbon dots (CDs) have been utilized to enhance the dispersibility in water and biological efficacy of Schiff bases. The amino groups on the surface of CDs were conjugated effectively with the aldehyde group of terephthalaldehyde to form novel CD-based Schiff bases (CDSBs). The results of the MTT assays demonstrate that CDSBs have significant anticancer activity in glioma GL261 cells and U251 cells, with IC50 values of 17.9 μg mL⁻¹ and 14.9 μg mL⁻¹, respectively. CDSBs have also been found to have good biocompatibility with normal glial cells. The production of reactive oxygen species (ROS) in GL261 glioma cells showed that CDSBs, at a concentration of 44 μg mL⁻¹, resulted in approximately 13 times higher intracellular ROS production than in the control group. These experiments offer evidence that CDSBs induce mitochondrial damage, leading to a reduction in mitochondrial membrane potential in GL261 cells. In particular, in this work, CDs serve not as carriers, but as an integral part of the anticancer drugs, which can expand the role of CDs in cancer treatment.

Background: As the most frequent type of cyanotic congenital heart disease (CHD), tetralogy of Fallot (TOF) has a relatively poor prognosis without corrective surgery. Circular RNAs (circRNAs) represent a novel class of endogenous noncoding RNAs that regulate target gene expression posttranscriptionally in heart development. Here, we investigated the potential role of the ceRNA network in the pathogenesis of TOF. Methods: To identify circRNA expression profiles in TOF, microarrays were used to screen the differentially expressed circRNAs between 3 TOF and 3 control human myocardial tissue samples. Then, a dysregulated circRNA-associated ceRNA network was constructed using the established multistep screening strategy. Results: In summary, a total of 276 differentially expressed circRNAs were identified, including 214 upregulated and 62 downregulated circRNAs in TOF samples. By constructing the circRNA-associated ceRNA network based on bioinformatics data, a total of 19 circRNAs, 9 miRNAs, and 34 mRNAs were further screened. Moreover, by enlarging the sample size, the qPCR results validated the positive correlations between hsa_circ_0007798 and HIF1A. Conclusions: The findings in this study provide a comprehensive understanding of the ceRNA network involved in TOF biology, such as the hsa_circ_0007798/miR-199b-5p/HIF1A signalling axis, and may offer candidate diagnostic biomarkers or potential therapeutic targets for TOF. In addition, we propose that the ceRNA network regulates TOF progression.