Toll-like receptor (TLR) pathways signal through microbial components stimulation to induce innate immune responses. Herein, we demonstrate that BCL10, a critical molecule that signals between the T cell receptor and IB kinase complexes, is involved in the innate immune system and is required for appropriate TLR4 pathway and nuclear factor-B (NF-B) activation. In response to lipopolysaccharide (LPS) stimulation, BCL10 was recruited to TLR4 signaling complexes and associated with Pellino2, an essential component downstream of BCL10 in the TLR4 pathway. In a BCL10-deficient macrophage cell line, LPS-induced NF-B activation was consistently defective, whereas activator protein-1 and Elk-1 signaling was intact. In addition, we found that BCL10 was targeted by SOCS3 for negative regulation in LPS signaling. The recruitment of BCL10 to TLR4 signaling complexes was attenuated by induced expression of SOCS3 in a feedback loop. Furthermore, ectopic SOCS3 expression blocked the interaction between BCL10 and Pellino2 together with BCL10-generated NF-B activation and inducible nitric-oxide synthase expression. Together, these data define an important role of BCL10 in the innate immune system.

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The COVID-19 pandemic has brought about significant influences to the world, including tunnel construction. Based on the analysis of 12 tunnel construction projects, this paper identifies the specific risk factors related to the COVID-19 pandemic, e.g., men, materials, machines, methods, social environment, and political epidemic prevention pressure. Among these risk factors, worker availability, site accessibility, shortage of construction materials, and inadequate epidemic prevention materials caused by the lockdown policy are the most fundamental challenges encountered by the projects. Social panic and epidemic prevention policy requirements are key issues needed to be addressed before the resumption of construction work. The special circumstances caused by the COVID-19 pandemic called for flexible project management and coordination skills to raise suitable and effective response strategies, while local governments make substantial contributions in solving the difficulties. Although these measures have resulted in higher project costs, their effectiveness in catching up with project schedules is worthy of recognition. The findings of this study enrich the risk categories of tunnel construction and the risk response strategies from the perspective of a global pandemic. It implies that future construction schemes including design, budget, supply chain, and project management should consider the possible influence of an epidemic.

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Site-specific recognition modules with DNA nuclease have tremendous potential as molecular tools for genome targeting. The type III transcription activator-like effectors (TALEs) contain a DNA binding domain consisting of tandem repeats that can be engineered to bind user-defined specific DNA sequences. We demonstrated that customized TALE-based nucleases (TALENs), constructed using a method called "unit assembly", specifically target the endogenous FRIGIDA gene in Brassica oleracea L. var. capitata L. The results indicate that the TALENs bound to the target site and cleaved double-strand DNA in vitro and in vivo, whereas the effector binding elements have a 23 bp spacer. The T7 endonuclease I assay and sequencing data show that TALENs made double-strand breaks, which were repaired by a non-homologous end-joining pathway within the target sequence. These data show the feasibility of applying customized TALENs to target and modify the genome with deletions in those organisms that are still in lacking gene target methods to provide germplasms in breeding improvement.