Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro

BACKGROUND Prohibitin 1(PHB1)has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed,and it participates in a variety of essential cellular functions,including apoptosis,cell cycle regulation,prolifera-tion,and survival.Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma(HCC).However,the role of PHB1 in HCC is controversial.AIM To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro.METHODS HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria;then,PHB1 levels in the sera and liver tissues of these participates were determined using ELISA,RT-PCR,and immunohistoche-mistry.Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA(shRNA-PHB1)for 24-72 h.Cell prolif-eration was analysed with an MTT assay.Cell cycle progression and apoptosis were analysed using flow cytometry(FACS).The mRNA and protein expression levels of the cell cycle-related molecules p21,Cyclin A2,Cyclin E1,and CDK2 and the cell apoptosis-related molecules cytochrome C(Cyt C),p53,Bcl-2,Bax,caspase 3,and caspase 9 were measured by real-time PCR and Western blot,respectively.RESULTS Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals,and decreased PHB1 was positively correlated with low differentiation,TNM stage III-IV,and alpha-fetoprotein≥400μg/L.Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner.FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis.The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells.The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41%±1.06%,which was significantly greater than that of apoptotic control cells(3.65%±0.85%,P<0.01)and empty vector-transfected cells(4.21%±0.52%,P<0.01).Similar results were obtained with SMMC-7721 cells.Furthermore,the mRNA and protein expression levels of p53,p21,Bax,caspase 3,and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2,Cy-clin E1,CDK2,and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells.However,when PHB1 was upregulated in human HCC cells,Cyt C expression levels were increased in the cytosol and decreased in the mitochondria,which indicated that Cyt C had been released into the cytosol.Conversely,these effects were reversed when PHB1 was knocked down.CONCLUSION PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.

Alkali-resistant NO_(x) reduction over FeVO_(4)/TiO_(2)catalysts via regulating the electron transfer between Fe and V

The presence of alkali metals in exhaust gas from stationary resources causes a grand challenge for the practical application of selective catalytic reduction(SCR)of NO_(x) with NH_(3).Here,alkali-resistant NO_(x) reduction has been successfully implemented via tailoring the electron transfer over Fe and V species on FeVO_(4)/TiO_(2)catalysts.The strong interaction between Fe and V induced electron transfer from V to Fe and strengthened the adsorption and activation of NH_(3)and NO over active VO_(x) sites.In the presence of K_(2)O,the strong electron withdrawing effect of Fe offset the electron donating effect of K on the VO_(x) species,thus protecting the active species VO_(x) to maintain the NO_(x) reduction ability.The enhanced adsorption and activation of NH_(3) allowed SCR reaction to proceed via E-R mechanism even after K_(2)O poisoning.This work elucidated the electronic effects on the alkali metals resistance of traditional ferric vanadate SCR catalysts and provided a promising strategy to design SCR catalysts with superior alkali resistance.

Unravelling the Anomalous Coking Resistance over Boron Nitride-Supported Ni Catalysts for Dry Reforming of Methane

Metal oxides have been used as the supports for heterogeneous catalysis formany years,but they still suffer from coking in some high-temperature applications.The main reasons for coking are the uncontrollable dissociation of C-H and the overbalance between carbon deposition and removal.Herein,we find a boron nitride(BN)-immobilized Ni catalyst shows unprecedented coking resistance in dry reforming of methane via the incomplete decomposition of methane.Unlike the Ni-based catalysts supported by traditional metal oxides,BN-supported Ni accelerates the first C-H dissociation while inhibiting the breaking of the final C-H bond;hence,the suppression of the complete decomposition of methane thoroughly addresses the coking issue.This work reveals the fundamental reason for the coking resistance over BN-supported Ni catalysts is selective activation of the C-H bond,which can provide an inspiring idea for other applications.

Refined analysis and a hierarchical multi-task learning approach for loan fraud detection

Fraud problems in loan application assessment cause significant losses for finance companies worldwide, and much research has focused on machine learning methods to improve the efficacy of fraud detection in some financial domains. However, diverse information falsification in individual fraud remains one of the most challenging problems in loan applications. To this end, we conducted an empirical study to explore the relationships between various fraud types and analyzed the factors influencing information fabrication. Weak relationships exist among different falsification types, and some essential factors play the same roles in different fraud types. In contrast, others have various or opposing effects on these types of frauds. Based on this finding, we propose a novel hierarchical multi-task learning approach to refine fraud-detection systems. Specifically, we first developed a hierarchical fraud category method to break down this problem into several subtasks according to the information types falsified by customers, reducing fraud identification's difficulty. Second, a heterogeneous network with a meta-path-based random walk and heterogeneous skip-gram model can solve the representation learning problem owing to the sophisticated relationships among the applicants' information. Furthermore, the final subtasks can be predicted using a multi-task learning approach with two prediction layers. The first layer provides the probabilities of general fraud categories as auxiliary information for the second layer, which is for specific subtask prediction. Finally, we conducted extensive experiments based on a real-world dataset to demonstrate the effectiveness of the proposed approach.