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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell apoptosis-inducing factor that can induce apoptosis in a variety of cancer cells. However, resistance to TRAIL in cancer cells is a huge obstacle in creating effective TRAIL-targeted clinical therapies. Thus, agents that can either enhance the effect of TRAIL or overcome its resistance are needed. In this study, we combined TRAIL with SNX-2112, an Hsp90 inhibitor we previously developed, to explore the effect and mechanism that SNX-2112 enhanced TRAIL-induced apoptosis in cervical cancer cells. Our results showed that SNX-2112 markedly enhanced TRAIL-induced cytotoxicity in HeLa cells, and this combination was found to be synergistic. Additionally, we found that SNX-2112 sensitized TRAIL-mediated apoptosis caspase-dependently in TRAIL-resistant HeLa cells. Mechanismly, SNX-2112 downregulated antiapoptosis proteins, including Bcl-2, Bcl-XL, and FLIP, promoted the accumulation of reactive oxygen species (ROS), and increased the expression levels of p-JNK and p53. ROS scavenger NAC rescued SNX-2112/TRAIL-induced apoptosis and suppressed SNX-2112-induced p-JNK and p53. Moreover, SNX-2112 induced the upregulation of death-receptor DR5 in HeLa cells. The silencing of DR5 by siRNA significantly decreased cell apoptosis by the combined effect of SNX-2112 and TRAIL. In addition, SNX-2112 inhibited the Akt/mTOR signaling pathway and induced autophagy in HeLa cells. The blockage of autophagy by bafilomycin A1 or Atg7 siRNA abolished SNX-2112-induced upregulation of DR5. Meanwhile, ROS scavenger NAC, JNK inhibitor SP600125, and p53 inhibitor PFTα were used to verify that autophagy-mediated upregulation of DR5 was regulated by the SNX-2112-stimulated activation of the ROS-JNK-p53 signaling pathway. Thus, the combination of SNX-2112 and TRAIL may provide a novel strategy for the treatment of human cervical cancer by overcoming cellular mechanisms of apoptosis resistance.

This paper applies Pirson and Malhotra's (2011) framework for organizational trust to data reuse in an educational context. Their framework delineates stakeholders along two axes: depth of the interactions (e.g., shallow or deep) and the locus of the relationship (e.g., internal or external). We analyzed 139 survey responses and 44 in-depth interviews with users of repositories holding video records of practice. We found that factors such as data quality, co-production of data between the repository and data producer, responsiveness of staff, and transparency of curation processes influenced trust, and that responsiveness and transparency were of particular importance for trust development for users with deeper interactions and a more internal loci of relationships to repositories.

Tin anode has great potential for sodium-ion batteries owing to its high theoretical capacity, but its tremendous volume expansion during the sodium (de)alloying processes leads to the structural degradation and cycling instability. Herein, we report a new design strategy by using low-cost enzymatic hydrolysis lignin-derived hard carbon as an ideal support for Sn particles dispersion. Sn can be uniformly anchored on the robust carbon substrate, to efficiently relieve Sn volume expansion upon cycling. In addition, conductive hard carbon support can facilitate electrons to transfer and further enhance Na + storage capacity and accelerate facile Na + diffusion in the Sn/C hybrid anodes. The resultant Sn/C hybrids as anodes deliver high-rate performance as well as distinguished cycling stability in view of high reversible capacity of 374 mAh g À1 at 20 mA g À1 and capacity retention of 91% at 1000 mA g À1 after 1000 cycles, benefiting from high electrical conductivity, highly dispersed Sn particles and suitable pore structure. This work is expected to provide fresh insight into cost-effective Sn-based anodes for sodium ion batteries.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy ubiquitously associated with Epstein–Barr virus (EBV). EBV generates various viral microRNAs (miRNAs) by processing the BHRF1 and BamHI A rightward (BART) transcripts. These BART miRNAs are abundantly expressed in NPC, but their functions and molecular mechanisms remain largely unknown. Our study found that the EBV-encoded microRNA BART-22 was significantly upregulated in NPC tissues and positively correlated with tumor progression. Furthermore, we found that EBV-miR-BART-22 was a significant predictor of poor prognosis in NPC. A reliable nomogram model to predict the preoperative overall survival (OS) of NPC patients was established. The area under the receiver operating characteristic (ROC) curve value for 5-year survival was 0.91. Elevated levels of EBV-miR-BART-22 significantly promoted the epithelial-mesenchymal transition (EMT) and metastasis of NPC cells in vivo and in vitro. We found that EBV-miR-BART-22 directly targets the 3′-UTR of MOSPD2 mRNA to promote the EMT and metastasis of NPC cells by activating the Wnt/β-catenin signaling pathway. Our findings provide a potential prognostic biomarker and new insight into the molecular mechanisms of NPC metastasis.

Longitudinally coupled prefabricated slab track is prone to slab warping under the non-uniform temperature field. Analytical expressions for the displacement field of the track slab during the warping process are developed hereby based on equilibrium differential equations, and the expressions are verified through a numerical model by finite element method in ANSYS package. Through analyzing the factors such as types of temperature distribution, slab gravity, and rail weight, regulations of warping deformation for the track slab are systematically analyzed. Research shows that the displacements in the x and z directions are linearly related to the respective components during the warping deformation. The displacement in y direction has a quadratic relationship with x and z components. Temperature gradient is the pivotal factor to lead the warping of the track slab, and the type of temperature distribution has less effect on the warping displacement. If track slab remains unwarped under the effect of slab gravity, temperature gradient should be maintained in the range of –18°C/m–13°C/m. Rail weight has less influence on slab warping.

We cast a suite of information extraction tasks into a text-to-triple translation framework. Instead of solving each task relying on taskspecific datasets and models, we formalize the task as a translation between task-specific input text and output triples. By taking the taskspecific input, we enable a task-agnostic translation by leveraging the latent knowledge that a pre-trained language model has about the task. We further demonstrate that a simple pretraining task of predicting which relational information corresponds to which input text is an effective way to produce task-specific outputs. This enables the zero-shot transfer of our framework to downstream tasks. We study the zero-shot performance of this framework on open information extraction (OIE2016, NYT, WEB, PENN), relation classification (FewRel and TACRED), and factual probe (Google-RE and T-REx). The model transfers non-trivially to most tasks and is often competitive with a fully supervised method without the need for any task-specific training. For instance, we significantly outperform the F1 score of the supervised open information extraction without needing to use its training set. 1