Experimental Study on Liquid Metal Embrittlement of Al-Zn-Mg Aluminum Alloy (7075): From Macromechanical Property Experiment to Microscopic Characterization.

This study is a multiscale experimental investigation into the embrittlement of Al-Zn-Mg aluminum alloy (7075-T6) caused by liquid metal gallium. The results of the experiment demonstrate that the tensile strength of the 7075-T6 aluminum alloy significantly weakens with an increase in the embrittlement temperature and a prolonged embrittlement time, whereas it improves with an increase in the strain rate. On the basis of the analysis of the experimental data, the sensitivity of the embrittlement of 7075-T6 aluminum alloy by liquid gallium to the loading strain rate is significantly higher compared to other environmental factors. In addition, this study also includes several experiments for microscopic observation, such as Scanning Electron Microscope (SEM) observation, Energy-Dispersive Spectrometer (EDS) spectroscopy, and Electron Back Scatter Diffraction (EBSD) analysis. The experimental observations confirmed the following: (1) gallium is enriched in the intergranular space of aluminum; (2) the fracture mode of 7075-T6 aluminum alloy changes from ductile to brittle fracture; and (3) the infiltration of liquid gallium into aluminum alloys and its enrichment in the intergranular space result in the formation of new dislocation nucleation sites, in addition to the original dislocations cutting and entanglement. This reduces the material's ability to undergo plastic deformation, intensifies stress concentration at the dislocation nucleation point, and, ultimately, leads to the evolution of dislocations into cracks.

Functional characterization of Vibrio alginolyticus T3SS regulator ExsA and evaluation of its mutant as a live attenuated vaccine candidate in zebrafish (Danio rerio) model.

Vibrio alginolyticus, a Gram-negative bacterium, is an opportunistic pathogen of both marine animals and humans, resulting in significant losses in the aquaculture industry. Type III secretion system (T3SS) is a crucial virulence mechanism of V. alginolyticus. In this study, the T3SS regulatory gene exsA, which was cloned from V. alginolyticus wild-type strain HY9901, is 861 bp encoding a protein of 286 amino acids. The ΔexsA was constructed by homologous recombination and Overlap-PCR. Although there was no difference in growth between HY9901 and ΔexsA, the ΔexsA exhibited significantly decreased extracellular protease activity and biofilm formation. Besides, the ΔexsA showed a weakened swarming phenotype and an ~100-fold decrease in virulence to zebrafish. Antibiotic susceptibility testing showed the HY9901ΔexsA was more sensitive to kanamycin, minocycline, tetracycline, gentamicin, doxycycline and neomycin. Compared to HY9901 there were 541 up-regulated genes and 663 down-regulated genes in ΔexsA, screened by transcriptome sequencing. qRT-PCR and ß-galactosidase reporter assays were used to analyze the transcription levels of hop gene revealing that exsA gene could facilitate the expression of hop gene. Finally, Danio rerio, vaccinated with ΔexsA through intramuscular injection, induced a relative percent survival (RPS) value of 66.7% after challenging with HY9901 wild type strain. qRT-PCR assays showed that vaccination with ΔexsA increased the expression of immune-related genes, including GATA-1, IL6, IgM, and TNF-α in zebrafish. In summary, these results demonstrate the importance of exsA in V. alginolyticus and provide a basis for further investigations into the virulence and infection mechanism.

TGF-ß signaling controls Foxp3 methylation and T reg cell differentiation by modulating Uhrf1 activity.

Regulatory T (T reg) cells are required for the maintenance of immune homeostasis. Both TGF-ß signaling and epigenetic modifications are important for Foxp3 induction, but how TGF-ß signaling participates in the epigenetic regulation of Foxp3 remains largely unknown. Here we showed that T cell-specific ablation of Uhrf1 resulted in T reg-biased differentiation in TCR-stimulated naive T cells in the absence of TGF-ß signaling, and these Foxp3+ T cells had a suppressive function. Adoptive transfer of Uhrf1 -/- naive T cells could significantly suppress colitis due to increased iT reg cell generation. Mechanistically, Uhrf1 was induced upon TCR stimulation and participated in the maintenance of DNA methylation patterns of T reg cell-specific genes during cell division, while it was phosphorylated upon TGF-ß stimulation and sequestered outside the nucleus, and ultimately underwent proteasome-dependent degradation. Collectively, our study reveals a novel epigenetic mechanism of TGF-ß-mediated iT reg cell differentiation by modulating Uhrf1 activity and suggests that Uhrf1 may be a potential therapeutic target in inflammatory diseases for generating stable iT reg cells.

Arp2/3 complex controls T cell homeostasis by maintaining surface TCR levels via regulating TCR+ endosome trafficking.

T cell receptor (TCR) signaling is important for T cell homeostasis and function. However, how surface TCR levels are regulated and its biological significance on T cells remains largely unknown. Here, we show that the T cell-specific deletion of Arpc2, a component of Arp2/3 complex, results in compromised peripheral T cell homeostasis. Arp2/3 complex-nucleated actin filaments are essential for maintaining surface TCR levels by regulating TCR+ endosome trafficking in resting state and controlling polarization of TCR+ endosomes during immune synapse formation in T cells. Additionally, Arpc2-TKO T cells are unable to form immune synapse. Interestingly, defected T cell homeostasis is caused by reduced surface TCR levels but not impaired immune synapse formation. Collectively, our findings suggest that Arp2/3 complex-nucleated actin filaments are required for maintaining surface TCR levels via regulating TCR+ endosome trafficking which is essential for T cell homeostasis.