A common host response to pathogen infection involves the production of robust interferons or proinflammatory cytokines to activate the JAK-STAT pathway, thereby limiting pathogen replication. The bacterial pathogen Legionella pneumophila creates an intracellular niche and evades host immunity utilizing a cohort of effectors by diverse biochemical activities, thereby permissive for its intracellular replication. However, roles of the JAK-STAT pathway during bacterial infection remain elusive. Here, we identify for the first time that L. pneumophila acetyltransferase effector Lem17 acts as a negative regulator of the JAK-STAT signaling. Lem17 directly interacts with JAK1 through a JAK1-binding Box1-like motif, preventing its recruitment by cytokine receptors. As a YopJ-family acetyltransferase, Lem17 catalyzes Nε-lysine acetylation of JAK1 and impairs its kinase activity, thereby disrupting JAK1-mediated signaling transduction. Our findings provide insights into the mechanism by which L. pneumophila subverts host immunity through acetylation and underscore the role of the JAK-STAT pathway against bacterial infection.
Building-integrated photovoltaics (BIPVs) is a promising application for semitransparent organic solar cells (ST-OSCs). However, conventional ultra-thin (<80 nm) active layers for ST-OSCs, while balancing transmittance and efficiency, limit the cell-to-module efficiency remaining ratio (CTM) below 56%. Here, we achieve high semitransparency and efficiency in ST-OSCs with reasonable active layer thickness by manipulating the aggregation of acceptors in various donor-diluted blends processed with non-halogen solvent in ambient air. Using PM6:Qx-p-4Cl as a model system, we elucidate a unique film-formation mechanism and charge generation process, demonstrating that the fiber network and suitable aggregation size are crucial for ensuring higher performance in donor-diluted ST-OSCs. The 1 cm2 donor-diluted ST-OSCs with active layer thicknesses of 119 and 301 nm exhibit high light utilization efficiencies (LUEs) of 4.04% and 3.02%, respectively. Notably, a 100 cm2 module demonstrates a CTM ratio of ~85% and a LUE of 3.32%, owing to its high film thickness tolerance, setting a new benchmark for large-area semitransparent modules. Furthermore, we demonstrate the feasibility of BIPVs in terms of power generation, energy storage, and temperature control through a scale-down model with a 600 cm2 power-generating window. These results reveal promising prospects for ST-OSCs in real-world applications.
Many GPCRs trigger a second phase of G protein-coupled signaling from endosomes after signaling from the plasma membrane, necessitating GPCRs to increase the concentration of active-state G proteins on the endosome membrane. How this is achieved remains unclear. Here, we show that three Gs-coupled GPCRs-the β2-adrenergic receptor, VIP-1 receptor, and adenosine 2B receptor-each trigger a net redistribution of Gαs from the plasma membrane to endosomes at native expression levels and without requiring receptor internalization. We then show that active-state Gαs production on endosomes, in contrast, is GPCR internalization-dependent. We further identify location bias in the selectivity of GPCR coupling between Gs and Gq on endosomes relative to the plasma membrane. We propose that endosomal Gs regulation involves discrete GPCR-G protein coupling reactions, one at the plasma membrane controlling Gs concentration and another at endosomes controlling Gs activity, and that GPCR endocytosis can switch signaling selectivity between G protein classes.
Organic electrosynthesis is a versatile and evergreen tool for constructing chemical compounds. However, the study of highly active electrodes has not received enough attention, which limits the further development of organic electrosynthesis. This work introduces a bottom-up route to prepare chitin-derived composite carbon aerogel electrodes (CCAEs), which can be directly used as electrodes in organic electrosynthesis systems. Various metal nanoparticles, such as Pt, Pd, RuO2, Cu and Ni, are well confined in these free-standing and porous CCAEs (M-CCAEs). The linear sweep voltammetry and in-situ Raman tests under electrochemical conditions show that RuO2-CCAEs possess good electrochemical oxidation ability for chlorine anions and good stabilizing effect on the generated chlorine radicals, which can serve as a mediator for the electrochemical C(sp3)-H activation. The combination of M-CCAEs with mediators achieves a series of electrochemical oxidative C(sp3)-H chlorination, bromination, nitration and etherification. Moreover, M-CCAEs promote the electrochemical hydrogen isotope exchange reaction of some important drug molecule structures, such as Ibuprofen, Diclofenac and Zolpidem.

