A Flexible Magnetic Soft Continuum Robot for Manipulation and Measurement at Microscale

Magnetic soft continuum robots have received interest in diverse fields, because of their active steering and remote control capabilities. However, a more challenging task is the development of magnetic soft continuum robots for analyzing the mechanical properties of biological tissue during intravascular treatments. Here, we present a force-controlled soft continuum robot with a magnetic end-effector for measurement of biological mechanical properties. The magnetically driven system contains a set of Helmholtz coils and a permanent magnet. The Helmholtz coils produce an oscillating magnetic field for overcoming friction. The permanent magnet is responsible for steering and providing traction for forward motion. The force on the magnetic tip was calibrated with a soft rod with a known elasticity coefficient. Experimental results indicated that the magnetic soft continuum robot successfully achieved manipulation and stiffness measurement of biological embryos. This strategy for mechanical property analysis of biological tissue expands the opportunities for use of soft continuum robots and broadens the field of functionalization for continuum microrobots

Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation

As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy

Effect of ageing on the microstructural evolution in a new design of maraging steels with carbon

A new maraging steel, based on carbide precipitation, is described. Two alloys were designed namely Fe-10Mn-0.25C-2Cr-1Mo wt% (2CrMo) and Fe-10Mn-0.25C-1Cr-2Mo wt% (Cr2Mo). These compositions were chosen to achieve ultra-high strength and high tensile elongation; the former and latter are promoted through the simulatenous precipitation of Cr- and Mo-rich carbides and Mn-rich reverted austenite. The alloys were manufactured through the standard melting, casting and hot working route. Following a solution treatment at 870 °C and quench, which gave a fully martensitic structure, the alloys were aged for various times at 510 °C. The microstructure and tensile properties were investigated in detail as a function of ageing time. The microstructure observed was dominated by micron scale and nanometre scale Mn segregation which determined the local Ac3 temperature. Austenite reversion occurred in both alloys, peaking at 16 h in both cases. In the 2CrMo alloy, the reverted austenite was mainly globular in morphology due the Ac3 temperature being lower than the ageing temperature, but was acicular in the Cr2Mo with Ac3 similar to the ageing temperature of 510 °C. Moreover, acicular austenite was promoted by Mn segregation at martensite lath boundaries in Cr2Mo. In the 2CrMo steel, carbide precipitation (M3C and M7C3) occurred during heating to the ageing temperature, but the carbides gradually dissolved with further ageing. In contrast, in the Cr2Mo alloy, precipitation of carbides (M7C3 and M2C) occurred during ageing, the volume fraction of which increased with ageing time. In both alloys a TRIP effect was observed, but the extent of this was greater for the Cr2Mo alloy. The complex microstructure obtained after 16 h led to an excellent combination of strength of 1.3 GPa and elongation of 18%. Physics-based models for the microstructure in martensite, precipitation kinetics, as well as for TRIP in austenite were employed to explain and predict the individual strengthtening contributions of the microstructure to the total strength, confirming that the maximum strength-elongation relationship found after 16 h is due to an optimal combination of a slightly overaged - but still strong- martensite and 30% of reverted austenite, for increased work hardening and ductility

What drives migration and who migrates : migration selectivity in the late 1990s in China

This thesis examines the migration selectivity of individuals in China in the late 1990s during the transition period from being a centrally planned economy to becoming a market-oriented one. It employs the micro data of China's fifth census conducted in 2000. In general, migration selectivity is determined by not only personal factors but also ecological attributes. Most notably, the institutional factors of the hukou system have led to a division of permanent migration versus temporary migration in China. This study integrates the economic theories of migration and the institutional approaches in a Chinese transitional context. At the individual level, the study reveals that Chinese migration remains a highly positive selection in terms of age and education due to the hukou division, contrary to the prediction of social capital theory and dual market theory for a less positive selective pattern. However, more females join the migration stream lending partial support to the latter two theories. At the macro level, the risk factor exerts a significantly strong and positive effect on migration propensity for rural laborers, though the regional differences in economic opportunities also have a positive effect. In addition, migration stocks, the social network proxy, also have a significantly positive effect strong enough to weed out any potential migrants