Clinical features and management of germline CEBPA-mutated carriers.

Familial acute myeloid leukemia (AML) pedigrees with germline CCAAT/enhancer-binding protein-α (CEBPA) mutation have been rarely reported due to insufficient knowledge of their clinical features. Here, we report two Chinese families with multiple AML cases carrying germline CEBPA mutations, one of which had 11 cases spanning four consecutive generations. Additionally, we collected clinical data of 57 AML patients from 22 families with germline CEBPA mutations, with 58.3% of them harboring double CEBPA mutations. The first mutation frequently occurred at the N-terminal of CEBP/α (78.6%), resulting in an exclusive expression of p30 of CEBPA (CEBPAp30). The second mutation was mostly found at the C-terminal of CEBP/α (CEBPAothers). Germline CEBPAp30 carriers had higher incidences of AML (80.36% vs. 42.86%) and earlier onset of AML (18 vs. 38.5 years old) compared to germline CEBPAothers carriers. Despite the high rates of relapse, most familial AML cases exhibited favorable overall survival (OS), with germline CEBPAp30 carriers having better survival outcomes (>25 years vs. 11 years for CEBPAothers carriers). Among the 27 healthy germline CEBPA-mutated carriers, we detected a pre-leukemia clone harboring a pathogenic IDH2 variant (R140Q)in one individual. These findings should aid in the genetic counseling and management of AML patients and healthy carriers with germline CEBPA mutations.

Recombinant GM-CSF enhances the bactericidal ability of PMNs by increasing intracellular IL-1ß and improves the prognosis of secondary Pseudomonas aeruginosa pneumonia in sepsis.

This study tested the hypothesis that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances polymorphonuclear neutrophils (PMNs) via interleukin (IL)-1ß to improve the prognosis of secondary infection in sepsis. The latter stage of sepsis is prone to induce immunosuppression, resulting in secondary fatal infections. Recombinant GM-CSF has become a way for sepsis-induced immunosuppression due to its immunomodulatory effect. However, the functional impact of GM-CSF on PMNs in sepsis remains obscure. This study aimed to study the role of recombinant GM-CSF on the bactericidal ability of PMNs in septic mice, assessing its effect on the prognosis of secondary pneumonia, and explore the mechanism of recombinant GM-CSF by intervening PMNs in patients with sepsis. The C57BL/6J sepsis mouse model was induced by cecal ligation and puncture. Recombinant murine GM-CSF (rmGM-CSF) was used in vivo when mice developed immunosuppression, which was characterized by abnormal bactericidal function of PMNs in peripheral blood. rmGM-CSF improved the prognosis of secondary pneumonia and reversed the function of PMNs. PMNs isolated by Percoll from septic patients were treated by recombinant human GM-CSF (rhGM-CSF) in vitro. The expression of CD11b, reactive oxygen species, phagocytosis, and neutrophil extracellular trap release in PMNs were enhanced by rhGM-CSF treatments. Whole-transcriptomic sequencing of mouse PMNs indicated that recombinant GM-CSF increased the expression of Il1b gene in PMNs. Blocking and inhibiting IL-1ß release effectively counteracted the enhancing effect of GM-CSF on the bactericidal function of PMNs. rmGM-CSF enhances the bactericidal function of PMNs in vivo and improves the prognosis of secondary pneumonia in septic mice, and recombinant GM-CSF increases IL-1ß precursor reserves, which, if stimulated, can rapidly enhance the bactericidal capacity of PMNs.

Dhx15 regulates zebrafish intestinal development through the Wnt signaling pathway.

DEAH-box helicase 15 (DHX15) is ATP-dependent RNA helicase which is known for its role in RNA metabolism. Recent studies reported DHX15 involves in the intestinal immunity. However, the role of DHX15 (or RNA helicase) in intestinal development is poorly understood. Here, we revealed an unidentified role for dhx15 in regulating zebrafish intestinal development. We found the profound intestinal defects in dhx15 knockout zebrafish. Decreased proliferation and increased apoptosis of the intestine cells were observed when dhx15 were deleted. Further RNA genome wide analysis and qRT-PCR analysis showed the Wnt signaling pathway is down-regulated in the dhx15 knockout zebrafish. Thus, we concluded that dhx15 regulates zebrafish intestinal development through the Wnt signaling pathway. Here, we provided new insights into the role of dhx15 in intestinal development beyond its well-characterized role in intestinal immunity.

Expression of PmACRE1 in Arabidopsis thaliana enables host defence against Bursaphelenchus xylophilus infection.

BACKGROUND: Pine wilt disease (PWD) is a destructive disease that endangers pine trees, resulting in the wilting, with yellowing and browning of the needles, and eventually the death of the trees. Previous studies showed that the Avr9/Cf-9 rapidly elicited (PmACRE1) gene was downregulated by Bursaphelenchus xylophilus infection, suggesting a correlation between PmACRE1 expression and pine tolerance. Here, we used the expression of PmACRE1 in Arabidopsis thaliana to evaluate the role of PmACRE1 in the regulation of host defence against B. xylophilus infection. RESULTS: Our results showed that the transformation of PmACRE1 into A. thaliana enhanced plant resistance to the pine wood nematode (PWN); that is, the leaves of the transgenic line remained healthy for a longer period than those of the blank vector group. Ascorbate peroxidase (APX) activity and total phenolic acid and total flavonoid contents were higher in the transgenic line than in the control line. Widely targeted metabolomics analysis of the global secondary metabolites in the transgenic line and the vector control line showed that the contents of 30 compounds were significantly different between these two lines; specifically, the levels of crotaline, neohesperidin, nobiletin, vestitol, and 11 other compounds were significantly increased in the transgenic line. The studies also showed that the ACRE1 protein interacted with serine hydroxymethyltransferase, catalase domain-containing protein, myrosinase, dihydrolipoyl dehydrogenase, ketol-acid reductoisomerase, geranylgeranyl diphosphate reductase, S-adenosylmethionine synthase, glutamine synthetase, and others to comprehensively regulate plant resistance. CONCLUSIONS: Taken together, these results indicate that PmACRE1 has a potential role in the regulation of plant defence against PWNs.

Kaolinite weakens the co-stress of ampicillin and tetracycline on Escherichia coli through multiple pathways.

Ampicillin and tetracycline are common antibiotics and can threaten humans by inducing antibiotic resistance in bacteria. Microorganisms are usually exposed to a mixed antibiotic system in the environment. However, there are few researches on the specific regulatory mechanisms of clay on microorganisms under the stress of complex antibiotics. In this study, tandem mass tag-based coupled with two-dimensional liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) was employed to recognize and quantify changes in protein expression of Escherichia coli (E. coli) after culture for 15 days, with or without kaolinite in the co-stress of ampicillin and tetracycline. The results indicated that kaolinite could activate metabolic pathways of E. coli such as the energy metabolism, the biosynthesis of other secondary metabolites, and the metabolism of cofactors and vitamins. Particularly, the fatty acid degradation pathway has also been promoted, indicating that in the same unfavorable environment, kaolinite might influence the composition of E. coli cell membranes. This might be due to the change in membrane composition that was a kind of adaptive strategy of bacterial evolution. Moreover, kaolinite could promote multidrug efflux system to export the bacterial intracellular toxic substances, making E. coli survive better in an adverse environment. Consequently, this study not only disclosed the regulation of kaolinite on E. coli in a complex antibiotic environment but also provided new insights into the environmental process of antibiotic resistance.

Prognostic value and susceptibility of BAX rs4645878 polymorphism in cancer: A systematic review and meta-analysis.

BACKGROUND: BCL-2 Associated X (BAX) is an important modulator of apoptosis. The associations between BAX gene polymorphism and cancer susceptibility and prognosis in different ethnic groups and types of cancer have yielded controversial results. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the associations. METHODS: A systematic search of Medline database (PubMed), EMBASE, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang databases for publications on BAX polymorphisms, and susceptibility and prognosis was carried out until July 2017. Retrieved 14 articles met the inclusions. Summary odds ratios (ORs) and hazard ratios (HRs) with their 95% confidence intervals (CIs) were harnessed to determine the strength of correlation between BAX polymorphisms and cancer susceptibility and prognosis, which were combined using fixed- or random-effects models as appropriate. RESULTS: A total of 12 trials involving 3321 cases and 3209 controls were included in our pooled analysis regarding the polymorphisms and the susceptibility of cancers. Overall, results of the present meta-analysis demonstrated that there was no significant association between BAX polymorphisms and susceptibility of cancers (OR = 1.052, 95% CI: 0.827-1.339, P = .679, A vs G). Even in a stratified analysis by ethnicity and the sources of control groups, the results were consistent. Four retrospective studies of 549 cases qualified for meta-analysis were identified to set forth the associations of the polymorphisms with cancer prognosis. Our results suggested that BAX gene polymorphisms were significantly associated with unfavorable prognosis (HR = 1.735, 95% CI: 1.368-2.202, P = .000, GG vs GA/AA). CONCLUSION: There is no significant association between BAX gene polymorphism and cancer susceptibility, but it probably contributes to increased adverse prognosis to cancer.

Immobilization of Sphingomonas sp. GY2B in polyvinyl alcohol-alginate-kaolin beads for efficient degradation of phenol against unfavorable environmental factors.

In this study, batch experiments were carried out to evaluate the biodegradation of phenol by Sphingomonas sp. GY2B, which were immobilized in polyvinyl alcohol (PVA)-sodium alginate-kaolin beads under different conditions. The optimal degradation performance was achieved by GY2B immobilized in beads containing 1.0% (w/v) of kaolin, 10% (w/v) of PVA, 0.3% (w/v) of sodium alginate, 10% (v/v) of biomass dosage, and exposed to an initial phenol concentration of 100 mg/L. The experimental results indicated that PVA-sodium alginate-kaolin beads can accelerate the degradation rate of phenol by reducing the degradation time and also improve degradation rate. The biodegradation rate of phenol by immobilized cells (16.79 ±â€¯0.81 mg/(L·h)) was significantly higher than that of free cells (11.49 ±â€¯1.29 mg/(L·h)) under the above optimal conditions. GY2B immobilized on beads was more competent than free GY2B in degradation under conditions with high phenol concentrations (up to 300 mg/L) and in strong acidic (pH = 1) and alkaline (pH = 12) environments. Higher phenol concentrations inhibit the biomass and reduce the biodegradation rate, while the lower biodegradation rate at low initial phenol concentrations is attributed to mass transfer limitations. The Haldane inhibitory model was in agreement with the experimental data well, revealing that phenol showed a considerable inhibitory effect on the biodegradation by Sphingomonas sp. GY2B, especially at concentrations higher than 90 mg/L. Intra-particle diffusion model analysis suggests that adsorption of phenol by immobilized beads was controlled by both rapid surface adsorption as well as pore diffusion mechanism. It's worth noting that the presence of 1 mg/L Cr(VI) enhanced the biodegradation of phenol by free cells, while Cr(VI) showed no obvious impact on the removal of phenol by immobilized cells. In addition, immobilized cells were reused 16 times and removed 99.5% phenol, and when stored at 4 °C for 90 days, more than 99% phenol was removed. These results showed that immobilized cells can significantly improve the microbial degradation performance, and protect microorganisms against unfavorable environment. It is implied that PVA -sodium alginate-kaolin beads have great potential to be applied in a practical and economical phenolic wastewater treatment system.

Differential regulation of phenanthrene biodegradation process by kaolinite and quartz and the underlying mechanism.

Natural and cost-effective materials such as minerals can serve as supportive matrices to enhance biodegradation of polycyclic aromatic hydrocarbons (PAHs). In this study we evaluated and compared the regulatory role of two common soil minerals, i.e. kaolinite and quartz in phenanthrene (a model PAH) degradation by a PAH degrader Sphingomonas sp. GY2B and investigated the underlying mechanism. Overall kaolinite was more effective than quartz in promoting phenanthrene degradation and bacterial growth. And it was revealed that a more intimate association was established between GY2B and kaolinite. Si and O atoms on mineral surface were demonstrated to be involved in GY2B-mineral interaction. There was an higher polysaccharide/lipid content in the EPS (extracellular polymeric substances) secreted by GY2B on kaolinite than on quartz. Altogether, these results showed that differential bacterial growth, enzymatic activity, EPS composition as well as the interface interaction may explain the effects minerals have on PAH biodegradation. It was implicated that different interface interaction between different minerals and bacteria can affect microbial behavior, which ultimately results in different biodegradation efficiency.

Synthesis and characterization of Fullerene modified ZnAlTi-LDO in photo-degradation of Bisphenol A under simulated visible light irradiation.

In this study, ZnAlTi layered double hydroxide (ZnAlTi-LDH) combined with fullerene (C60) was fabricated by the urea method, and calcined under vacuum atmosphere to obtain nanocomposites of C60-modified ZnAlTi layered double oxide (ZnAlTi-LDO). The morphology, structure and composition of the nanocomposites were analyzed by Scanning Electron Microscopy, High-resolution transmission electron microscopy, X-ray diffraction patterns, Fourier transform infrared and specific surface area. The UV-vis diffuse reflectance spectra indicated that the incorporation of C60 expanded the absorption of ZnAlTi-LDO to visible-light region. The photo-degradation experiment was conducted by using a series of C60 modified ZnAlTi-LDO with different C60 weight percentage to degrade Bisphenol A (BPA) under simulated visible light irradiation. In this experiment, the degradation rate of C60 modified ZnAlTi-LDO in photo-degradation of BPA under simulated visible light irradiation was over 80%. The intermediates formed in the degradation of BPA process by using LDO/C60-5% were 4-hydroxyphenyl-2-propanol, 4-isopropenylphenol and Phenol. Photogenerated holes, superoxide radical species, ·OH and singlet oxygen were considered to be responsible for the photodegradation process, among which superoxide radical species and ·OH played a predominant role in the photocatalytic reaction system. C60 modified ZnAlTi-LDO catalysts for photocatalytic reduction shows great potential in degradation of organic pollutants and environmental remediation.

Correction: Efficient Removal of Co2+ from Aqueous Solution by 3-Aminopropyltriethoxysilane Functionalized Montmorillonite with Enhanced Adsorption Capacity.

[This corrects the article DOI: 10.1371/journal.pone.0159802.].

Efficient Removal of Co2+ from Aqueous Solution by 3-Aminopropyltriethoxysilane Functionalized Montmorillonite with Enhanced Adsorption Capacity.

To achieve a satisfactory removal efficiency of heavy metal ions from wastewater, silane-functionalized montmorillonite with abundant ligand-binding sites (-NH2) was synthesized as an efficient adsorbent. Ca-montmorillonite (Ca-Mt) was functionalized with 3-aminopropyl triethoxysilane (APTES) to obtain the APTES-Mt products (APTES1.0CEC-Mt, APTES2.0CEC-Mt, APTES3.0CEC-Mt, APTES4.0CEC-Mt) with enhanced adsorption capacity for Co2+. The physico-chemical properties of the synthesized adsorbents were characterized by spectroscopic and microscopic methods, and the results demonstrated that APTES was successfully intercalated into the gallery of Ca-Mt or grafted onto the surface of Ca-Mt through Si-O bonds. The effect of solution pH, ionic strength, temperature, initial concentrations and contact time on adsorption of Co2+ by APTES-Mt was evaluated. The results indicated that adsorption of Co2+ onto Ca-Mt, APTES1.0CEC-Mt and APTES2.0CEC-Mt can be considered to be a pseudo-second-order process. In contrast, adsorption of Co2+ onto APTES3.0CEC-Mt and APTES4.0CEC-Mt fitted well with the pseudo-first-order kinetics. The adsorption isotherms were described by the Langmuir model, and the maximum adsorption capacities of APTES1.0CEC-Mt, APTES2.0CEC-Mt, APTES3.0CEC-Mt and APTES4.0CEC-Mt were 25.1, 33.8, 61.6, and 61.9 mg·g-1, respectively. In addition, reaction temperature had no impact on the adsorption capacity, while both the pH and ionic strength significantly affected the adsorption process. A synergistic effect of ion exchange and coordination interactions on adsorption was observed, thereby leading to a significant enhancement of Co2+ adsorption by the composites. Thus, APTES-Mt could be a cost-effective and environmental-friendly adsorbent, with potential for treating Co2+-rich wastewater.

Evaluation of poly(styrene-alt-maleic anhydride)-ethanol as enteric coating material.

This study aims at evaluating the potential of SMA-ethanol as enteric coating polymer for erythromycin tablets. SMA-ethanol was synthesized and characterized for physicochemical properties, molecular weight and thermal analysis. Free films were prepared by adding different kinds and amounts of plasticizers, the film surface topography was determined by a SEM, the tensile strength, water vapor transmission rate and moisture absorption were also tested to choose the most promising film. DBP was proved to be the most suitable plasticizer with a best using amount of 20%, such polymer films had low vapor transmission rate and low moisture absorption which were very important to an enteric coating material. The polymer was further characterized for film coating by evaluating the release of erythromycin tablets in vitro, tablets coated with SMA-ethanol can satisfy the drug release requests of USP when the film weight gains were between 4 and 6%; tablets coated with both a subcoat and the polymer showed excellent gastro-resistance, less than 0.2% drug release occurred even with weight gains as less as 2% after 2h exposure to acid (pH 1), while over 90% drug release occurred in pH 6.8 sodium phosphate buffer within 45 min, regardless of weight gains of coating material, moreover, we confirmed that the application of a subcoat could decrease the amount of required coating polymer. In conclusion, the potential use of SMA-ethanol as enteric coating material was demonstrated.