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.     

Microstructure and mechanical behavior of laser aided additive manufactured low carbon interstitial Fe49.5Mn30Co10Cr10C0.5 multicomponent alloy

Laser aided additive manufacturing(LAAM)was used to fabricate bulk Fe49.5Mn30Co10Cr10C0.5 interstitial multicomponent alloy using pre-alloyed powder.The room temperature yield strength(σy),ultimate tensile strength(σUTS)and elongation(εUST)were 645 MPa,917 MPa and 27.0％respectively.The as-built sample consisted of equiaxed and dendritic cellular structures formed by elemental segregation.These cellular structures together with oxide particle inclusions were deemed to strengthen the material.The other contributing components include dislocation strengthening,friction stress and grain bound-ary strengthening.The high εUTS was attributed to dislocation motion and activation of both twinning and transformation-induced plasticity(TWIP and TRIP).Tensile tests performed at-40℃and-130℃demonstrated superior tensile strength of 1041 MPa and 1267 MPa respectively.However,almost no twinning was observed in the fractured sample tested at-40℃and-130℃.Instead,higher fraction of strain-induced hexagonal close-packed(HCP)ε phase transformation of 21.2％were observed for fractured sample tested at-40℃,compared with 6.3％in fractured room temperature sample.     

Stable Radicals with Protective Umbrellas Integrated on the Surface of 2D Layered Materials

Radicals are closely related to human life and health and have been widely used in biology, chemistry, functional materials, etc. However, the high reactivity, disorder, and short half-lives limit their wide applications. Therefore, it remains a great challenge to prepare stable and ordered radicals. Herein, radicals are prepared with protective umbrellas (diethylmethyleneamine, DEMA) that are integrated on the surface of 2D layered materials to isolate water and oxygen and enhance the stability of radicals. Taking 2D black phosphorus (BP) as an example: triethylamine reacts with dichloromethane to form quaternary ammonium salts with further Hoffmann elimination to produce DEMA radicals that could react with one electron of a lone pair electrons in P on the surface of BP to produce P radicals, which shows a prolonged half-life of 21 days at room temperature. First-principle calculations and electron paramagnetic resonance fitting confirm that the steric hindrance constructed by dense DEMA passivation layer acts as a protective umbrella and the 2D coupling of P radicals and other P atoms in 2D BP plane to enhance the stability and strong superexchange interaction of P radicals. Furthermore, it is a general strategy to produce stable radicals integrated on the 2D plane.     

Equilibrium consumption and portfolio decisions with stochastic discount rate and time-varying utility functions

OR Spectrum - This paper studies a multi-period investment–consumption optimization problem with a stochastic discount rate and a time-varying utility function, which are governed by a...     

Biomimetic Lamellar Chitosan Scaffold for Soft Gingival Tissue Regeneration

Mucogingival surgery has become a common procedure for soft gingival tissue reparation in dental clinical practice, which mainly relies on autograft or commercial collagen membranes (CM). However, the autograft faces grand challenges in source availability and long-term post-surgery pain management, and the CM is restricted by its poor mechanical properties in an aqueous environment. Here, it is reported that a bio-inspired lamellar chitosan scaffold (LCS) with long range ordered porous structure, manufactured through a bidirectional freezing method, can serve as a promising gingival tissue engineering material. The LCS not only exhibits excellent mechanical properties in the hydrated state but also accelerates vessel formation and soft tissue regeneration in vivo. Most interestingly, the LCS is found to be capable of inducing macrophage differentiation to M2 macrophages, which is thought to play an important role in tissue regeneration. These advantages combined with its easy and low-cost preparation process make the LCS a promising candidate for dental clinical applications.     

A review of CO2 sorbents for promoting hydrogen production in the sorption-enhanced steam reforming process

Sorption-enhanced-steam-reforming (SESR) is a thermochemical conversion technology that produces a high-purity hydrogen stream by utilizing in-situ removal of CO₂ with a sorbent. In this paper, the advantages and disadvantages of CaO based sorbents, alkali-metal based sorbents (Na₂ZrO₃, Li₂ZrO₃ and Li₄SiO₄), hydrotalcite based sorbents, bifunctional materials and sorbents prepared from wastes are briefly discussed, and the techniques to improve the sorption properties of these CO₂ sorbents are summarized. In the process of hydrogen production by sorption-enhanced-steam-reforming, the selection of suitable high-temperature CO₂ sorbent is the key to produce high purity hydrogen. Furthermore, the hydrogen-production performance of the above-mentioned sorbents in the SESR process is investigated and summarized. Finally, a future perspective and some suggestions regarding these five types of sorbents are put forward.     

偶联反应器格栅的制作和组装工艺

格栅支持板是换热器中的主要部件,尤其是大尺寸的格栅支持板,以前国内没有先例,如何编制好它的制作工艺和程序,并且在实际过程中得到很好的执行,遇到问题及时调整处置,对它的加工、组装、和整体安装有着特别重要的作用。