Cell death is an essential regulatory mechanism for removing unneeded cells in animal development and tissue homeostasis. The c-Jun N-terminal kinase (JNK) pathway has pivotal roles in the regulation of cell death in response to various intrinsic and extrinsic stress signals. The canonical Wingless (Wg) signaling has been implicated in cell proliferation and cell fate decisions, whereas its role in cell death remains largely elusive. Here, we report that activated Bsk (the Drosophila JNK homolog) induced cell death is mediated by the canonical Wg signaling. First, loss of Wg signaling abrogates Bsk-mediated caspase-independent cell death. Second, activation of Wg signaling promotes cell death in a caspase-independent manner. Third, activation of Bsk signaling results in upregulated transcription of wingless (wg) gene. Finally, Wg pathway participates in the physiological function of Bsk signaling in development. These findings not only reveal a previously undiscovered role of Wg signaling in Bsk-mediated cell death, but also provide a novel mechanism for the interplay between the two important signaling pathways in development.
Abbreviations:Fut1, a-2 fucosyltransferase I; Fut2, a-2 fucosyltransferase II; Sec1, a-2 fucosyltransferase III; Blood group H, Fuc a2 Gal b; Blood group A, GalNAc a3 Fuc a2 Gal b; Blood group B, Gal a3 Fuc a2 Gal b; CFG, consortium of functional glycomics; Lewis y, Fuc a2 Gal b4 (a3) GlcNAc b; Type I H, Fuc a2 Gal b3 GlcNAc b; Type II H, Fuc a2 Gal b4 GlcNAc b; Type III H, Fuc a2 Gal b3 GalNAc a;Type IV H, Fuc a2 Gal b3 GalNAc b;Type VI H, Fuc a2 Gal b4 Glc b AbstractThe fucose alpha(1,2) galactose structure (H antigen) is synthesized by a1,2 fucosyltransferases Fut1, Fut2 and Sec1. H antigen has been reported to be involved in cancer progression, neurite migration, synaptic plasticity, host-microbe interaction, blastocyst implantation, and the maintenance of gut microbiome. Genetic depletion of Fut1 or Fut2 only cause defects of alpha1,2 fucosylation in limited tissues because of enzyme redundancy. In this study, we generated mice with deficiencies in Fut1, Fut2, and Sec1 genes to deplete H antigen through BAC Engineering for the generation of ES Cell-Targeting construct. The homogenous triple knockout mice showed no significant decrease of viability or development. Mass spectrometry and Western blot analysis confirmed the absence of H blood group antigen in multiple organs. These results indicate normal development and fertility of mice devoid of blood group H. The fine pathophysiological alterations in these mice remain to be carefully studied, and they may serve as valuable tools to study gut microbiome and host-microbe interactions.
Pulmonary ground glass nodules (GGNs) have been increasingly identified in past decades and is becoming an important clinical dilemma in oncology. Meanwhile, humans persistently inhale microplastics which are dominant in the air. However, the retention of “non-self” microplastics in human lung and its correlation with pulmonary GGNs remains elusive. In this study, we firstly demonstrated the presence of microfibers and microplastics in human lung, with higher detection rates in GGNs in comparison to those in normal tissue. Moreover, both types and colors of microfibers in tumor were richer than those in normal tissues. Intriguingly, high risk of microfibers exposure predisposes the formation of pulmonary GGN. Further, increased roughness surface was observed in microfibers isolated in human lung, indicating the possible link of surface roughness to the formation of pulmonary GGN. Collectively, our findings reveal an emerging role of environmental microplastics exposure in the etiology of pulmonary GGN.One Sentence SummaryThe exposure of environmental microplastics is a risk factor of pulmonary GGN.
Quorum sensing inhibitors (QSIs) are promising alternatives to antibiotics, but they are discharged into the environment after their use cycle. This poses joint effects on the organisms in the environment. Therefore, it is of great importance to study the combined toxicities of QSIs and antibiotics. In this study, we investigated the single and combined toxicities of four potential QSIs and 11 sulfonamides (SAs) on Escherichia coli. The results revealed that the single toxicities of SAs were greater than those of QSIs, and the toxicities were found positively related to the binding energies (E) with their target proteins, for both antibiotics and QSIs. The combined toxicities of the binary mixtures were observed to be either antagonism or addition. The antagonism could be explained by the phenomenon that QSIs changed SAs molecules into ionic forms, preventing the SA molecules entering the bacteria. Furthermore, it was found that the ratios of the effective concentration (the actual concentration involved in the interaction with the proteins) in the antagonistic cases were higher than those in the additive cases. This study would benefit both rational use of the drug combination and ecological risk assessment of antibiotics and QSIs in the real environment.
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