Ribosome Quality Control mitigates the cytotoxicity of ribosome collisions induced by 5-Fluorouracil.

Ribosome quality control (RQC) resolves collided ribosomes, thus preventing their cytotoxic effects. The chemotherapeutic agent 5-Fluorouracil (5FU) is best known for its misincorporation into DNA and inhibition of thymidylate synthase. However, while a major determinant of 5FU's anticancer activity is its misincorporation into RNAs, the mechanisms by which cancer cells overcome the RNA-dependent 5FU toxicity remain ill-defined. Here, we report a role for RQC in mitigating the cytotoxic effects of 5FU. We show that 5FU treatment results in rapid induction of the mTOR signalling pathway, enhanced rate of mRNA translation initiation, and increased ribosome collisions. Consistently, a defective RQC exacerbates the 5FU-induced cell death, which is mitigated by blocking mTOR pathway or mRNA translation initiation. Furthermore, 5FU treatment enhances the expression of the key RQC factors ZNF598 and GIGYF2 via an mTOR-dependent post-translational mechanism. This adaptation likely mitigates the cytotoxic consequences of increased ribosome collisions upon 5FU treatment.

Design and Realization of Triple dsDNA Nanocomputing Circuits in Microfluidic Chips.

DNA logic gates, nanocomputing circuits, have already implemented basic computations and shown great signal potential for nano logic material application. However, the reaction temperature and computing speed still limit its development. Performing complicated computations requires a more stable component and a better computing platform. We proposed a more stable design of logic gates based on a triple, double-stranded, DNA (T-dsDNA) structure. We demonstrated a half adder and a full adder using these DNA nanocircuits and performed the computations in a microfluidic chip device at room temperature. When the solutions were mixed in the device, we obtained the expected results in real time, which suggested that the T-dsDNA combined microfluidic chip provides a concise strategy for large DNA nanocircuits.

Dynamic Softening and Hardening Behavior and the Micro-Mechanism of a TC31 High Temperature Titanium Alloy Sheet within Hot Deformation.

TC31 is a new type of α+ß dual phase high temperature titanium alloy, which has a high specific strength and creep resistance at temperatures from 650 °C to 700 °C. It has become one of the competitive candidates for the skin and air inlet components of hypersonic aircraft. However, it is very difficult to obtain the best forming windows for TC31 and to form the corresponding complex thin-walled components. In this paper, high temperature tensile tests were carried out at temperatures ranging from 850 °C to 1000 °C and strain rates ranging from 0.001 s-1 to 0.1 s-1, and the microstructures before and after deformation were characterized by an optical microscope, scanning electron microscope, and electron back-scatter diffraction. The dynamic softening and hardening behaviors and the corresponding micro-mechanisms of a TC31 titanium alloy sheet within hot deformation were systematically studied. The effects of deformation temperature, strain rate, and strain on microstructure evolution were revealed. The results show that the dynamic softening and hardening of the material depended on the deformation temperature and strain rate, and changed dynamically with the strain. Obvious softening occurred during hot tensile deformation at a temperature of 850 °C and a strain rate of 0.001 s-1~0.1 s-1, which was mainly caused by void damage, deformation heat, and dynamic recrystallization. Quasi-steady flowing was observed when it was deformed at a temperature of 950 °C~1000 °C and a strain rate of 0.001 s-1~0.01 s-1 due to the relative balance between the dynamic softening and hardening. Dynamic hardening occurred slightly with a strain rate of 0.001 s-1. Mechanisms of dynamic recrystallization transformed from continuous dynamic recrystallization to discontinuous dynamic recrystallization with the increase in strain when it was deformed at a temperature of 950 °C and a strain rate of 0.01 s-1. The grain size also decreased gradually due to the dynamic recrystallization, which provided an optimal forming condition for manufacturing thin-walled components with the desired microstructure and an excellent performance.

A Specific Nucleic Acid Microfluidic Capture Device Based on Stable DNA Nanostructure.

Benefiting from superior programmability and good biocompatibility, DNA nanomaterials have received considerable attention with promising prospects in biological detection applications. However, their poor stability and operability severely impede further development of the applications of DNA nanomaterials. Here, a thermally stable DNA nanomesh structure is integrated into a microfluidic chip. The specificity of the nucleic acid microfluidic capture device could reach the single-base mismatch level while capturing the ssDNA sample. The microfluidic chip provides a closed environment for the DNA nanomesh, giving the device excellent storage stability. After 6 months of storage at room temperature, the device still has a specific capture function on ssDNA samples with low concentration. The specific nucleic acid microfluidic capture device can be applied to the enrichment of ctDNA in the future and contribute to the early diagnosis of cancer.

High Pressure Pneumatic Forming of Ti-3Al-2.5V Titanium Tubes in a Square Cross-Sectional Die.

A new high strain rate forming process for titanium alloys is presented and named High Pressure Pneumatic Forming (HPPF), which might be applicable to form certain tubular components with irregular cross sections with high efficiency, both with respect to energy cost and time consumption. HPPF experiments were performed on Ti-3Al-2.5V titanium alloy tubes using a square cross-sectional die with a small corner radius. The effects of forming of pressure and temperature on the corner filling were investigated and the thickness distributions after the HPPF processes at various pressure levels are discussed. At the same time, the stress state, strain and strain rate distribution during the HPPF process were numerically analyzed by the finite element method. Microstructure evolution of the formed tubes was also analyzed by using electron back scattering diffraction (EBSD). Because of different stress states, the strain and strain rate are very different at different areas of the tube during the corner filling process, and consequently the microstructure of the formed component is affected to some degree. The results verified that HPPF is a potential technology to form titanium tubular components with complicated geometrical features with high efficiency.