circFAM193B interaction with PRMT6 regulates AML leukemia stem cells chemoresistance through altering the oxidative metabolism and lipid peroxidation.

Most forms of chemotherapy for acute myeloid leukemia (AML) are often ineffective in eliminating leukemic stem cells (LSCs), as their underlying mechanisms remain unclear. Here, we have identified circFAM193B, which regulates the redox biology of LSCs and is associated with unfavorable outcomes in AML patients. In vitro and in vivo assays suggested that circFAM193B significantly inhibits LSCs chemotherapy resistance and AML progression. Knockdown circFAM193B enhances mitochondrial OXPHOS function and inhibits the accumulation of reactive oxygen species and lipid peroxidation mediated by chemotherapy, which protects AML cells from oxidative stress-induced cell death. Mechanistically, circFAM193B physically interacts with arginine methyltransferase PRMT6 catalytic domain and enhances the transcription efficiency of key lipid peroxidation factor ALOX15 by decreasing H3R2me2a modification. In summary, we have identified circFAM193B was downregulated in LSCs to promote the survival of LSC by modulating energy metabolism and the redox balance in the postchemotherapy persistence of LSC. Our studies provide a conceptual advance and biological insights regarding the drug resistance of LSCs via circRNA mediated PRMT6-deposited methylarginine signaling.

Analysis of gene mutation characteristics and its correlation with prognosis in patients with myelodysplastic syndromes.

Gene mutations are a pivotal component of the pathogenesis of MDS, and they hold profound prognostic significance for predicting treatment responses and survival outcomes. However, reports about mutation patterns in Chinese MDS patients are limited. In this study, we analyzed the genetic mutation of 23 genes in 231 patients with MDS using next-generation sequencing (NGS) technology, and explored the characteristics of gene mutations in MDS patients and their associations with clinical outcomes, survival, and transformation outcomes. Our results showed that 68.83% patients had at least one gene mutation, and the most common mutations were ASXL1 (21.65%), SF3B1 (17.32%), U2AF1 (16.02%), TET2 (14.72%) and TP53 (8.66%). We also showed that the genetic mutations of TP53, U2AF1 and DNMT3A are independent risk factors for death in patients with MDS, and the ETV6 gene mutation was an independent risk factor for the transformation of MDS patients to AML through the univariate and multivariate Cox regression analysis model. Additionally, the study developed a risk score based on gene mutation data that demonstrated robust predictive capability and stability for the overall survival of MDS patients. Our research provided a strong theoretical basis for the establishment of personalized treatment and prognostic risk assessment models for Chinese MDS patients.

Mitochondrial transfer in hematological malignancies.

Mitochondria are energy-generated organelles and take an important part in biological metabolism. Mitochondria could be transferred between cells, which serves as a new intercellular communication. Mitochondrial transfer improves mitochondrial defects, restores the biological functions of recipient cells, and maintains the high metabolic requirements of tumor cells as well as drug resistance. In recent years, it has been reported mitochondrial transfer between cells of bone marrow microenvironment and hematological malignant cells play a critical role in the disease progression and resistance during chemotherapy. In this review, we discuss the patterns and mechanisms on mitochondrial transfer and their engagement in different pathophysiological contexts and outline the latest knowledge on intercellular transport of mitochondria in hematological malignancies. Besides, we briefly outline the drug resistance mechanisms caused by mitochondrial transfer in cells during chemotherapy. Our review demonstrates a theoretical basis for mitochondrial transfer as a prospective therapeutic target to increase the treatment efficiency in hematological malignancies and improve the prognosis of patients.

Hematopoietic stem cells suppress proliferation and enhance differentiation of leukemia cells through regulating apoptotic and inflammatory genes.

PURPOSE: Stem cells are known to play an important role in tumor treatment and many of them have shown tumor-suppressing ability in different cancers; however, whether hematopoietic stem cells (HSCs) have growth-inhibiting effects on leukemia cells has not been fully evaluated. Herein, we aimed to demonstrate the growth-restraining function of HSCs in acute leukemia treatment. METHODS: Cell fusion experiment was conducted by PEG-1500. The viability, proliferation, apoptosis and differentiation of leukemia cells were evaluated by cell counting, CCK-8 and flow cytometry analysis. The morphological changes were imaged using a fluorescence microscope. The expression of genes was detected by quantitative reverse transcription PCR (qRT-PCR). RESULTS: We observed that HSCs and their lytic extracts had the capability to suppress leukemia cells proliferation, promote apoptosis and especially induce acute myelogenous leukemia (AML) cells differentiation, which might have an effect on differentiation therapy to leukemia especially AML treatment. The expression levels of Bcl-2, Survivin decreased and Bax increased following HSCs extracts treatment. Furthermore, the expression of inflammatory cytokines also changed in AML cells which might have to do with the mechanism of HSCs/extracts suppressing effect. CONCLUSION: HSCs and their extracts can suppress the proliferation of leukemia cells and enhance the differentiation of AML cells and using the extracts of HSCs might be a probable therapeutic option for acute leukemia.

Lattice Strain Engineering of Ni2 P Enables Efficient Catalytic Hydrazine Oxidation-Assisted Hydrogen Production.

Hydrazine-assisted water electrolysis provides new opportunities to enable energy-saving hydrogen production while solving the issue of hydrazine pollution. Here, the synthesis of compressively strained Ni2 P as a bifunctional electrocatalyst for boosting both the anodic hydrazine oxidation reaction (HzOR) and cathodic hydrogen evolution reaction (HER) is reported. Different from a multistep synthetic method that induces lattice strain by creating core-shell structures, a facile strategy is developed to tune the strain of Ni2 P via dual-cation co-doping. The obtained Ni2 P with a compressive strain of -3.62% exhibits significantly enhanced activity for both the HzOR and HER than counterparts with tensile strain and without strain. Consequently, the optimized Ni2 P delivers current densities of 10 and 100 mA cm-2 at small cell voltages of 0.16 and 0.39 V for hydrazine-assisted water electrolysis, respectively. Density functional theory (DFT) calculations reveal that the compressive strain promotes water dissociation and concurrently tunes the adsorption strength of hydrogen intermediates, thereby facilitating the HER process on Ni2 P. As for the HzOR, the compressive strain reduces the energy barrier of the potential-determining step for the dehydrogenation of *N2 H4 to *N2 H3 . Clearly, this work paves a facile pathway to the synthesis of lattice-strained electrocatalysts via the dual-cation co-doping.

EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway.

Aberrant expression of circRNAs has been proven to play a crucial role in the progression of acute myeloid leukemia (AML); however, its regulatory mechanism remains unclear. Herein, we identified a novel circRNA, Circ_0001187, which is downregulated in AML patients, and its low level contributes to a poor prognosis. We further validated their expression in large-scale samples and found that only the expression of Circ_0001187 was significantly decreased in newly diagnosed (ND) AML patients and increased in patients with hematological complete remission (HCR) compared with controls. Knockdown of Circ_0001187 significantly promoted proliferation and inhibited apoptosis of AML cells in vitro and in vivo, whereas overexpression of Circ _0001187 exerted the opposite effects. Interestingly, we found that Circ_0001187 decreases mRNA m6A modification in AML cells by enhancing METTL3 protein degradation. Mechanistically, Circ_0001187 sponges miR-499a-5p to enhance the expression of E3 ubiquitin ligase RNF113A, which mediates METTL3 ubiquitin/proteasome-dependent degradation via K48-linked polyubiquitin chains. Moreover, we found that the low expression of Circ _0001187 is regulated by promoter DNA methylation and histone acetylation. Collectively, our findings highlight the potential clinical implications of Circ _0001187 as a key tumor suppressor in AML via the miR-499a-5p/RNF113A/METTL3 pathway.

Fast preparation of a polydopamine/ceramic composite nanofiltration membrane with excellent permselectivity.

Fabrication of a dense polymer/ceramic composite membrane with high permeability remains a great challenge. In this study, a highly selective polydopamine (PDA)/ceramic composite nanofiltration (NF) membrane was prepared by using an Al2O3 ceramic membrane with pore size of 0.1 µm as the support layer. In order to improve the membrane formation rate, KMnO4 was introduced to oxidize the dopamine to improve the reactivity, and Na2CO3 was used to adjust the pH value of the dopamine solution. When the addition amount of KMnO4 is 0.2 g L-1 and that of Na2CO3 is 1 g L-1, a functional layer can be formed within 10 min. PDA and polyethyleneimine (PEI) were added to the functional layer to adjust the selectivity of the composite membrane. The composite membrane showed a rejection of 99.7% towards Congo red dye with a high flux of 165 L (m2 h bar)-1 at ambient temperature. After 3 h treatment with Congo red, the fouling resistance of the membrane was improved compared with that of the ceramic based membrane. The surface morphology and composition of the composite membrane were also characterized with scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), which confirmed the successful preparation of the PDA/ceramic composite membrane.

Single and simultaneous effects of naphthalene and salinity on anaerobic digestion: Response surface methodology, microbial community analysis and potential functions prediction.

Polycyclic aromatic hydrocarbons (PAHs) are a persistent and prevalent class of pollutants in petroleum-contaminated saline environment, which pose potential harm to organisms. Researches on anaerobic biodegradation of PAHs are gradually emerging, but the response of anaerobic microorganisms to salinity changes and the co-effects of salinity and PAHs in anaerobic digestion (AD) system have seldom been reported. Thus, we investigated the variations of AD system performance and anaerobic microbial community caused by different concentrations of naphthalene (Nap) or/and NaCl based on Box-Behnken Design (0 mg/L ≤ Nap ≤150 mg/L, 0 g/L ≤ NaCl ≤25 g/L). The promoted efficiencies of acidogenesis and methanogenesis were found in presence of moderate NaCl or Nap, but high salinity (NaCl >4.4 g/L) weakened AD performance. Moreover, the high salinity (NaCl >4.4 g/L) and Nap resulted in reduced microbial Ca2+ Mg2+- ATPase activity, poor EPS secretion and the highest difference of the microbial operational taxonomic units (OTUs), and synergistically inhibited AD process. Microbiological analysis revealed that the relative abundance of Clostridium and acetoclastic Methanosaeta was increased by 2.01 times and 2.17 times in single Nap treated group compared to control. With the simultaneous addition of NaCl and Nap, Proteiniphilum and hydrogenotrophic methanogens (Methanobacterium, Methanofollis, and Methanolinea) occupied the major abundance. Potential functions prediction indicated that high salinity could disrupt the co-metabolism between carbohydrate metabolism and Nap degradation. This study provides basis for anaerobic bioremediation of PAHs-polluted saline environment.

Learning from COVID-19: Infectious Disease Vulnerability Promotes Pro-Environmental Behaviors.

Environmental problems, such as climate change, pollution, and environmental degradation, are important contributors to the spread of infectious diseases, such as COVID-19 and SARS. For instance, a greater concentration of ambient NO2 was associated with faster transmission of the SARS-CoV-2 virus, which causes COVID-19. However, it remains unclear whether outbreaks of infectious diseases arouse individuals' concern on the need to protect the environment and therefore promote more pro-environmental behaviors. To this end, we examined the relationship between infectious disease vulnerability and pro-environmental behaviors using data from a cross-societal survey (N = 53 societies) and an experiment (N = 214 individuals). At both the societal and the individual levels, infectious disease vulnerability increased pro-environmental behaviors. At the societal level, this relationship was mediated by citizens' level of environmental concern. At the individual level, the relationship was mediated by empathy. The findings show that infectious disease vulnerability is conducive to pro-environmental behaviors.

Investigation of the process stability of different anammox configurations and assessment of the simulation validity of various anammox-based kinetic models.

Over the last 30 years, the successful implementation of the anammox process has attracted research interest from all over the world. Various reactor configurations were investigated for the anammox process. However, the construction of the anammox process is a delicate topic in regards to the high sensitivity of the biological reaction. To better understand the effects of configurations on the anammox performance, process-kinetic models and activity kinetic models were critically overviewed, respectively. A significant difference in the denitrification capabilities was observed even with similar dominated functional species of anammox with different configurations. Although the kinetic analysis gained insight into the feasibility of both batch and continuous processes, most models were often applied to match the kinetic data in an unsuitable manner. The validity assessment illustrated that the Grau second-order model and Stover-Kincannon model were the most appropriate and shareable reactor-kinetic models for different anammox configurations. This review plays an important role in the anammox process performance assessment and augmentation of the process control.

Developing a Reliable Service System of Charity Donation During the Covid-19 Outbreak.

Drawing upon the functional characteristics of blockchain technology, this article envisages the feasibility and reliability of developing a charity donation service system loaded onto blockchain in response to the complex service demands encountered by charity operators due to the Covid-19 epidemic. With blockchain technology's support as the underlying data book, this article focuses on the practical issues of charity donation fund and material allocation, as well as information release and sharing, charity donation organization, and organization self-management. The paper thereby discusses the key technologies in terms of overall structure design, specific service sector, and functional design of the donation service system and further summarizes the operational mechanism of the system as combined with the needs of help-seeking, receiving, and management users. It is argued that all the above proposals have the potential to alleviate the trust crisis of charity services in China in view of low transparency. The paper expects to provide a useful reference for charity business innovation propelled by blockchain technology.

Application of CPI cutoff value based on parentage testing of duos and trios typed by four autosomal kits.

In this study, we analyzed the application of four autosomal kits and the sensitivity of the combined paternity index (CPI) cutoff value (CPI≥10000) in parentage testing. First, 1442 real trios and 803 real duos were tested using the Goldeneye 25A kit. The Goldeneye 25A kit covers the autosomal short tandem repeat (STR) loci of the other three kits, so we calculated the CPI value of every case for the four kits. Second, three complex close relative kinship cases were also analyzed to evaluate the application of the CPI cutoff value. The CPI values of all trio cases were higher than 10000 using the four kits; the CPI values of all duo cases were higher than 10000 using the Goldeneye 25A kit; and the CPI values of a portion of the duo cases were lower than 10000 using the other three kits. In the three complex close relative cases, the alleged father or mother was not excluded using 40 autosomal STRs. Adding X chromosome short tandem repeats (X-STR) and samples of biological fathers or mothers, the conclusions were confirmed. The four kits were adequate to draw conclusions in the trio cases; the Goldeneye 25A Kit was adequate to draw conclusions in the duo cases; and the other three kits were not sufficient for a portion of the duo cases. The CPI cutoff value was sensitive for real trio and duo cases. In complex close relative kinship cases, high CPI values may result in false conclusions.