Enhanced photocatalytic degradation of ciprofloxacin over Bi2O3/(BiO)(2)CO3 heterojunctions: Efficiency, kinetics, pathways, mechanisms and toxicity evaluation

In this study, the degradation of antibiotic ciprofloxacin (CIP) over Bi2O3/(BiO)(2)CO3 heterojunctions under simulated solar light irradiation (SSL-Bi2O3/(BiO)(2)CO3) was examined for the first time. The results showed that the Bi2O3/(BiO)(2)CO3 heterojunctions dramatically improved CIP decay efficiency. The effect of parameters showed that the CIP decay was optimized with the Bi2O3/(BiO)(2)CO3 dosage of 0.5 g/L and a wide pH range of 4.0-8.3, based on which, a kinetic model was derived to predict the remaining CIP concentration. It was found that the presence of anions like SO42-, NO3- and HCO3- decelerated the CIP decay, while the co-existence of Cl- accelerated the CIP decay. Six degradation intermediates were identified by ultra-performance liquid chromatography coupled with mass analyzer (UPLC/MS) and ion chromatographic (IC) analysis, and the decay pathways and degradation mechanism of CIP were proposed by combining the experiment data with theoretical calculation of frontier electron densities. Hydroxyl radical's reaction, photo-hole (h(+)) oxidation and reductive defluorination were found to involve in the CIP decay. The efficient alleviation on total organic carbon (TOC) and toxicity indicated that the complete mineralization and de-toxicity are possible by this system with sufficient reaction time

Cloning, over-expression, and characterization of a new carboxypeptidase A gene of Bacillus pumilus ML413 in Bacillus subtilis 168

Carboxypeptidase A (CPAs) are a well-studied group of zinc-containing exopeptidases that facilitate thebreakdown of proteins and peptides during metabolism. Carboxypeptidase A is typically produced in mammalian pancreatic, brain and other tissues. A new gene encoding carboxypeptidase A in the prokaryote Bacillus pumilus was amplified by polymerase chain reaction (PCR), ligated into the shuttle vector pMA5, and cloned in a GRAS bacteria-Bacillus subtilis 168 host. This gene sequence contained a 1621 bp open reading frame that encodes a protein of 540 amino acids. The optimum pH and temperature for enzyme activity were 7.5 and 50°C, respectively. The enzyme was quite stable at neutral pH and maintained about 65% activity following a 24 h incubation at 40°C. The Km of this CPA was 0.1 mM, much higher than in mammalian species. Glycerol, ammonium sulfate, and sodium citrate improved enzyme activity under optimal culture condition. The carboxypeptidase activity in recombinant B. subtilis 168 reached a maximum of 179 U ml-1 in a 5 L fermentator when cultured on improved medium. The over expression of  carboxypeptidase A in Bacillus subtilis has commercial applications.Key words: Bacillus pumilus, Bacillus subtilis 168, over-expression, orthogonal arrays, carboxypeptidase A,metallocarboxypeptidase

Gene therapy for C-26 colon cancer using heparin-polyethyleneimine nanoparticle-mediated survivin T34A

Ling Zhang1,*, Xiang Gao1,2,*, Ke Men1, BiLan Wang1, Shuang Zhang1, Jinfeng Qiu1, Meijuan Huang1, MaLing Gou1, Ning Huang2, ZhiYong Qian1, Xia Zhao1, YuQuan Wei11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, 2Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workBackground: Gene therapy provides a novel method for the prevention and treatment of cancer, but the clinical application of gene therapy is restricted, mainly because of the absence of an efficient and safe gene delivery system. Recently, we developed a novel nonviral gene carrier, ie, heparin-polyethyleneimine (HPEI) nanoparticles for this purpose.Methods and results: HPEI nanoparticles were used to deliver plasmid-expressing mouse survivin-T34A (ms-T34A) to treat C-26 carcinoma in vitro and in vivo. According to the in vitro studies, HPEI nanoparticles could efficiently transfect the pGFP report gene into C-26 cells, with a transfection efficiency of 30.5% ± 2%. Moreover, HPEI nanoparticle-mediated ms-T34A could efficiently inhibit the proliferation of C-26 cells by induction of apoptosis in vitro. Based on the in vivo studies, HPEI nanoparticles could transfect the Lac-Z report gene into C-26 cells in vivo. Intratumoral injection of HPEI nanoparticle-mediated ms-T34A significantly inhibited growth of subcutaneous C-26 carcinoma in vivo by induction of apoptosis and inhibition of angiogenesis.Conclusion: This research suggests that HPEI nanoparticle-mediated ms-T34A may have a promising role in C-26 colon carcinoma therapy.Keywords: gene therapy, mouse survivin-T34A, colon cancer, polyethyleneimine, nanoparticles, cancer therap

A novel stemness classification in acute myeloid leukemia by the stemness index and the identification of cancer stem cell-related biomarkers

BackgroundStem cells play an important role in acute myeloid leukemia (AML). However, their precise effect on AML tumorigenesis and progression remains unclear.MethodsThe present study aimed to characterize stem cell-related gene expression and identify stemness biomarker genes in AML. We calculated the stemness index (mRNAsi) based on transcription data using the one-class logistic regression (OCLR) algorithm for patients in the training set. According to the mRNAsi score, we performed consensus clustering and identified two stemness subgroups. Eight stemness-related genes were identified as stemness biomarkers through gene selection by three machine learning methods.ResultsWe found that patients in stemness subgroup I had a poor prognosis and benefited from nilotinib, MK-2206 and axitinib treatment. In addition, the mutation profiles of these two stemness subgroups were different, which suggested that patients in different subgroups had different biological processes. There was a strong significant negative correlation between mRNAsi and the immune score (r= -0.43, p<0.001). Furthermore, we identified eight stemness-related genes that have potential to be biomarkers, including SLC43A2, CYBB, CFP, GRN, CST3, TIMP1, CFD and IGLL1. These genes, except IGLL1, had a negative correlation with mRNAsi. SLC43A2 is expected to be a potential stemness-related biomarker in AML.ConclusionOverall, we established a novel stemness classification using the mRNAsi score and eight stemness-related genes that may be biomarkers. Clinical decision-making should be guided by this new signature in prospective studies

Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications

The development of coagulation factor VIII (FVIII) inhibitory antibodies is a serious complication in hemophilia A (HA) patients after FVIII replacement therapy. Inhibitors render regular prophylaxis ineffective and increase the risk of morbidity and mortality. Immune tolerance induction (ITI) regimens have become the only clinically proven therapy for eradicating these inhibitors. However, this is a lengthy and costly strategy. For HA patients with high titer inhibitors, bypassing or new hemostatic agents must be used in clinical prophylaxis due to the ineffective ITI regimens. Since multiple genetic and environmental factors are involved in the pathogenesis of inhibitor generation, understanding the mechanisms by which inhibitors develop could help identify critical targets that can be exploited to prevent or eradicate inhibitors. In this review, we provide a comprehensive overview of the recent advances related to mechanistic insights into anti-FVIII antibody development and discuss novel therapeutic approaches for HA patients with inhibitors

The fibrinogen-to-albumin ratio is associated with intracranial atherosclerosis plaque enhancement on contrast-enhanced high-resolution magnetic resonance imaging

BackgroundContrast-enhanced high-resolution magnetic resonance imaging (CE-HR-MRI) is a useful imaging modality to assess vulnerable plaques in intracranial atherosclerotic stenosis (ICAS) patients. We studied the relationship between the fibrinogen-to-albumin ratio (FAR) and plaque enhancement in patients with ICAS.MethodsWe retrospectively enrolled consecutive ICAS patients who had undergone CE-HR-MRI. The degree of plaque enhancement on CE-HR-MRI was evaluated both qualitatively and quantitatively. Enrolled patients were classified into no enhancement, mild enhancement, and obvious enhancement groups. An independent association of the FAR with plaque enhancement was identified by multivariate logistic regression and receiver operating characteristic (ROC) curve analyses.ResultsOf the 69 enrolled patients, 40 (58%) were classified into the no/mild enhancement group, and 29 (42%) into the obvious enhancement group. The obvious enhancement group had a significantly higher FAR than the no/mild enhancement group (7.36 vs. 6.05, p = 0.001). After adjusting for potential confounders, the FAR was still significantly independently associated with obvious plaque enhancement in multiple regression analysis (odds ratio: 1.399, 95% confidence interval [CI]: 1.080–1.813; p = 0.011). ROC curve analysis revealed that FAR >6.37 predicted obvious plaque enhancement with 75.86% sensitivity and 67.50% specificity (area under the ROC curve = 0.726, 95% CI: 0.606–0.827, p < 0.001).ConclusionThe FAR can serve as an independent predictor of the degree of plaque enhancement on CE-HR-MRI in patients with ICAS. Also, as an inflammatory marker, the FAR has potential as a serological biomarker of intracranial atherosclerotic plaque vulnerability