Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Single transition metal atom catalysts on Ti2CN2 for efficient CO2 reduction reaction

Electrochemical CO₂ reduction reaction (CO₂RR) is an efficient way in the utilization of CO₂. In this work, single transition-metal (TM) atom (TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn) anchored on two-dimensional (2D) Ti₂CN₂ are designed for CO₂RR using density-functional-theory (DFT) calculation. We show that Ti₂CN₂ serves as an excellent substrate to support single atom catalysts (SACs), compared to Ti₂CO₂ and Ti₂CF₂. We find that the Sc, Ti and V supported on Ti₂CN₂ show high catalytic activities to produce CO with a low overpotential of 0.37, 0.27, and 0.23 eV, respectively. Differently, the Mn and Fe on Ti₂CN₂ are catalytically active for the production of HCOOH with a low overpotential of 0.32 and 0.43 eV, respectively. We further show that the negatively charged TM-Ti₂CN₂ can capture and activate CO₂ more effectively, and the catalytic activity and selectivity can be significantly tuned by injecting extra electrons.     

Optimal Water Allocation of Surface and Ground Water Resources Under Climate Change with WEAP and IWOA Modeling

Water Resources Management - The water evaluation and planning (WEAP) approach and the invasive weed optimization algorithm (IWOA) are herein employed to determine the optimal operating policies in...     

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

Electricity rates for the zero marginal cost grid

The electricity industry is rapidly changing: costs are increasingly dominated by capital and technology is turning loads into resources. This is similar to the early days of the Internet. Building on rate-structures used in the communications industry, utilities of the future should offer customers a portfolio of service contract options that provide a signal to the utility regarding the type and amount of infrastructure that should be deployed.     

3D finite element simulation model of a chemiresistor gas sensor based on ZnO and graft comb copolymer integrated in a gas chamber

Journal of Materials Science: Materials in Electronics - In this paper, chemiresistor sensor based on conductive polymer (regio-regular poly(3- hexyltiophene) (rr-P3HT) and zinc oxide (ZnO)...     

Appropriate energy efficient building envelope technologies for social housing in the Irish climate

Extensive dynamic thermal simulation parametric analyses have been undertaken of energy efficient fabric alterations to social housing in Northern Ireland culminating in priorities for deployment. Five ȁ8basecaseȁ9 simulation models were used to represent the predominant characteristics of the existing social housing stock. The majority of technologies studied provided annual space-heating energy savings of more than 10%. The variation of energy savings and economic performance across the basecases highlights the value of a dwelling specific approach to selecting energy efficient building envelope technology solutions for energy rehabilitation programmes. The paper further outlines a framework for prioritising appropriate energy efficient building envelope technological solutions for a large regional building stock, i.e. existing social housing stock in Northern Ireland, highlighting influential parameters. An energy efficient building envelope inter-technology ranking approach provides a method of comparison across the various different dwellings in the regional housing stock. Airtightness ranked consistently highest across the dwellings studied with some solar technologies performing better than more technologically mature solutions such as insulation.