The role of liver receptor homologue-1 (LRH-1) in breast cancer

Estrogens play a critical role in the development and progression of breast cancer. The biological functions of estrogen are mainly mediated by estrogen receptors (ER), which act by regulating gene expression in breast cancer cells. Previously our laboratory identified liver receptor homologue-1 (LRH-1), a member of the nuclear receptor superfamily of transcription factors to which ER also belongs, as an estrogen-responsive gene. Subsequent work showed that LRH-1 is important in mediating the growth of breast cancer cells. Herein, I show that LRH-1 in turn regulates the expression of ERα, providing a positive feedback loop, which may act to promote stable co-expression of ERα and LRH-1 in breast cancer cells. To better define the mechanisms of LRH-1 action in breast cancer cells, gene expression microarray analysis was performed following RNA interference mediated LRH-1 knockdown. Microarray analysis demonstrated that LRH-1 regulates the expression of many estrogen-responsive genes. ChIP-seq analysis, carried out to identify global LRH-1 binding sites, showed that LRH-1 is recruited to a substantial proportion of estrogen-regulated genes, frequently binding to ERα binding sites, suggesting LRH-1 directly regulates a subset of ERα-target genes in breast cancer cells. Analysis of select binding sites confirmed the direct LRH-1 regulation of ERα target genes through LRH-1 binding to estrogen response elements (ERE), as exemplified by the TFF1/pS2 gene. Moreover, LRH-1 was shown to stimulate the recruitment of ERα to the ERE in the shared/common target genes, suggesting a co-operative function between LRH-1 and ERα. Collectively, these findings show that LRH-1 is a key mediator of the estrogen response in breast cancer cells and raises the possibility of targeting LRH-1 for the treatment of breast cancer. Towards this end, I also describe the identification of novel LRH-1 antagonists that inhibit breast cancer cell growth. Development of these compounds will offer investigational tools for validating the importance of LRH-1 in breast cancer, towards a therapeutic strategy in breast cancer treatment.Open Acces

Catalytic thermal degradation of Chlorella Vulgaris: Evolving deep neural networks for optimization

The aim of this study is to identify the optimum thermal conversion of Chlorella vulgaris with neuro-evolutionary approach. A Progressive Depth Swarm-Evolution (PDSE) neuro-evolutionary approach is proposed to model the Thermogravimetric analysis (TGA) data of catalytic thermal degradation of Chlorella vulgaris. Results showed that the proposed method can generate predictions which are more accurate compared to other conventional approaches (>90% lower in Root Mean Square Error (RMSE) and Mean Bias Error (MBE)). In addition, Simulated Annealing is proposed to determine the optimal operating conditions for microalgae conversion from multiple trained ANN. The predicted optimum conditions were reaction temperature of 900.0 °C, heating rate of 5.0 °C/min with the presence of HZSM-5 zeolite catalyst to obtain 88.3% of Chlorella vulgaris conversion

Catalytic thermal degradation of Chlorella Vulgaris: Evolving deep neural networks for optimization

The aim of this study is to identify the optimum thermal conversion of Chlorella vulgaris with neuro-evolutionary approach. A Progressive Depth Swarm-Evolution (PDSE) neuro-evolutionary approach is proposed to model the Thermogravimetric analysis (TGA) data of catalytic thermal degradation of Chlorella vulgaris. Results showed that the proposed method can generate predictions which are more accurate compared to other conventional approaches (>90% lower in Root Mean Square Error (RMSE) and Mean Bias Error (MBE)). In addition, Simulated Annealing is proposed to determine the optimal operating conditions for microalgae conversion from multiple trained ANN. The predicted optimum conditions were reaction temperature of 900.0 °C, heating rate of 5.0 °C/min with the presence of HZSM-5 zeolite catalyst to obtain 88.3% of Chlorella vulgaris conversion

Elucidation of single atom catalysts for energy and sustainable chemical production: Synthesis, characterization and frontier science

The emergence of single atom sites as a frontier research area in catalysis has sparked extensive academic and industrial interest, especially for energy, environmental and chemicals production processes. Single atom catalysts (SACs) have shown remarkable performance in a variety of catalytic reactions, demonstrating high selectivity to the products of interest, long lifespan, high stability and more importantly high atomic metal utilization efficiency. In this review, we unveil in depth insights on development and achievements of SACs, including (a) Chronological progress on SACs development, (b) Recent advances in SACs synthesis, (c) Spatial and temporal SACs characterization techniques, (d) Application of SACs in different energy and chemical production, (e) Environmental and economic aspects of SACs, and (f) Current challenges, promising ideas and future prospects for SACs. On a whole, this review serves to enlighten scientists and engineers in developing fundamental catalytic understanding that can be applied into the future, both for academia or valorizing chemical processes

LRH-1 drives colon cancer cell growth by repressing the expression of the <i>CDKN1A</i> gene in a p53-dependent manner

Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that has been implicated in the progression of breast, pancreatic and colorectal cancer (CRC). To determine mechanisms underlying growth promotion by LRH-1 in CRC, we undertook global expression profiling following siRNA-mediated LRH-1 knockdown in HCT116 cells, which require LRH-1 for growth and in HT29 cells, in which LRH-1 does not regulate growth. Interestingly, expression of the cell cycle inhibitor p21 (CDKN1A) was regulated by LRH-1 in HCT116 cells. p21 regulation was not observed in HT29 cells, where p53 is mutated. p53 dependence for the regulation of p21 by LRH-1 was confirmed by p53 knockdown with siRNA, while LRH-1-regulation of p21 was not evident in HCT116 cells where p53 had been deleted. We demonstrate that LRH-1-mediated p21 regulation in HCT116 cells does not involve altered p53 protein or phosphorylation, and we show that LRH-1 inhibits p53 recruitment to the p21 promoter, likely through a mechanism involving chromatin remodelling. Our study suggests an important role for LRH-1 in the growth of CRC cells that retain wild-type p53

Uncertainty estimation approach in catalytic fast pyrolysis of rice husk : Thermal degradation, kinetic and thermodynamic parameters study

The aim of this study was to understand the influence of catalyst in thermal degradation behavior of rice husk (RH) in catalytic fast pyrolysis (CFP) process. An iso-conversional Kissinger kinetic model was introduced into this study to understand the activation energy (EA), pre-exponential value (A), Enthalpy (ΔH), Entropy (ΔS) and Gibb’s energy (ΔG) of non-catalytic fast pyrolysis (NCFP) and CFP of RH. The study revealed that the addition of natural zeolite catalyst enhanced the rate of devolatilization and decomposition of RH associated with lowest EA value (153.10 kJ/mol) compared to other NCFP and CFP using nickel catalyst. Lastly, an uncertainty estimation was applied on the best fit non-linear regression model (MNLR) to identify the explanatory variables. The finding showed that it had the highest probability to obtain 73.8–74.0% mass loss in CFP of rice husk using natural zeolite catalyst

Life-cycle assessment of hydrogen production via catalytic gasification of wheat straw in the presence of straw derived biochar catalyst

The environmental footprints of H2 production via catalytic gasification of wheat straw using straw-derived biochar catalysts were examined. The functional unit of 1 kg of H2 was adopted in the system boundaries, which includes 5 processes namely biomass collection and pre-treatment units (P1), biochar catalyst preparation using fast pyrolysis unit (P2), two-stage pyrolysis-gasification unit (P3), products separation unit (P4), and H2 distribution to downstream plants (P5). Based on the life-cycle assessment, the hot spots in this process were identified, the sequence was as follows: P4 > P2 > P1 > P3 > P5. The end-point impacts score for the process was found to be 93.4017 mPt. From benchmarking analysis, the proposed straw-derived biochar catalyst was capable of offering almost similar catalytic performance with other metal-based catalysts with a lower environmental impact

Progress in thermochemical co-processing of biomass and sludge for sustainable energy, value-added products and circular economy

To achieve the main goal of net zero carbon emission, the shift from conventional fossil-based energy/products to renewable and low carbon-based energy/products is necessary. Biomass has been perceived as a carbon–neutral source from which energy and value-added products can be derived, while sludge is a slurry waste that inherently contains high amount of minerals and organic matters. Hence, thermochemical co-processing of biomass wastes and sludge could create positive synergistic effects, resulting in enhanced performance of the process (higher conversion or yield) and improved qualities or characteristics of the products as compared to that of mono-processing. This review presents the current progress and development for various thermochemical techniques of biomass-sludge co-conversion to energy and high-value products, and the potential applications of these products from circular economy’s point of view. Also, these technologies are discussed from economic and environmental standpoints, and the outlook towards technology maturation and successful commercialization is laid out

A systematic review of the molecular simulation of hybrid membranes for performance enhancements and contaminant removals

Number of research on molecular simulation and design has emerged recently but there is currently a lack of review to present these studies in an organized manner to highlight the advances and feasibility. This paper aims to review the development, structural, physical properties and separation performance of hybrid membranes using molecular simulation approach. The hybrid membranes under review include ionic liquid membrane, mixed matrix membrane, and functionalized hybrid membrane for understanding of the transport mechanism of molecules through the different structures. The understanding of molecular interactions, and alteration of pore sizes and transport channels at atomistic level post incorporation of different components in hybrid membranes posing impact to the selective transport of desired molecules are also covered. Incorporation of molecular simulation of hybrid membrane in related fields such as carbon dioxide (CO2) removal, wastewater treatment, and desalination are also reviewed. Despite the limitations of current molecular simulation methodologies, i.e., not being able to simulate the membrane operation at the actual macroscale in processing plants, it is still able to demonstrate promising results in capturing molecule behaviours of penetrants and membranes at full atomic details with acceptable separation performance accuracy. From the review, it was found that the best performing ionic liquid membrane, mixed matrix membrane and functionalized hybrid membrane can enhance the performance of pristine membrane by 4 folds, 2.9 folds and 3.3 folds, respectively. The future prospects of molecular simulation in hybrid membranes are also presented. This review could provide understanding to the current advancement of molecular simulation approach in hybrid membranes separation. This could also provide a guideline to apply molecular simulation in the related sectors