SARS-CoV-2 enhances complement-mediated endothelial injury via the suppression of membrane complement regulatory proteins.

Complement hyperactivation and thrombotic microangiopathy are closely associated with severe COVID-19. Endothelial dysfunction is a key mechanism underlying thrombotic microangiopathy. To address the relationship between endothelial injury, complement activation and thrombotic microangiopathy of severe COVID-19, we wonder whether, and if so, what and how SARS-CoV-2 factors make endothelial cells (ECs) sensitive to complement-mediated cytotoxicity.

Nuclear adenine activates hnRNPA2B1 to enhance antibacterial innate immunity.

Bacterial infection reprograms cellular metabolism and epigenetic status, but how the metabolic-epigenetic crosstalk empowers host antibacterial defense remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a sensor for metabolite adenine to launch an antimicrobial innate response through increasing Il1b transcription. Myeloid cell-specific Hnrnpa2b1-cKO mice are more susceptible to bacterial infection, while interleukin 1 beta (IL-1β) supplementation rescues the phenotype.

Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1.

Deciphering mechanisms for cancer immune escape may provide targets for improving immunotherapy efficacy. By in vivo genome-wide CRISPR loss-of-function screening in a mouse model of triple negative breast cancer (TNBC), we uncovered a non-classical function of Cd28 in cancer cells to promote immune escape. Knocking out Cd28 in cancer cells increased infiltration of type I conventional DC (cDC1) and activated tumor-specific CD8 T cells, and pharmaceutical inducible knockdown of Cd28 inhibited pre-established tumor growth and overcame anti-PD-1 resistance in vivo.

Single-cell spatiotemporal analysis of the lungs reveals Slamf9 macrophages involved in viral clearance and inflammation resolution.

How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages.

Rapid and efficient removal of organophosphorus pollutant and recovery of valuable elements: A boosted strategy for eliminating organophosphorus from wastewater.

Considering the significant hazards of organophosphorus compounds (OPs) and the potential crisis of phosphorus (P) resource shortage, there is a great necessity to develop economically feasible, highly effective, and sustainable strategies to remove OPs and recover P resources. In this study, low-cost microscale zero-valent iron (mZVI) was used to activate hydrogen peroxide for the rapid and efficient elimination of Tetrakis(hydroxymethyl)phosphonium sulfate (THPS) from the aquatic environment. Compared to the conventional Fenton reaction and commercial mZVI, mZVI/HO-based Fenton-like reaction exhibited superior removal performance for THPS.

Identification of immune-activating metabolite for enhancing T cell therapy of cancer.

In this Research Highlight, we summarized the results from a study by Wu et al. published in Nature Cell Biology which uncovered that asparagine (Asn), a non-essential amino acid in mammalians, is able to enhance the TCR-mediated activation and efficacy of CD8 T cells towards tumour through lymphocyte-specific protein tyrosine kinase (LCK) signalling. This study provides insights into the physiological function of Asn in T cell activation and effector functions, showing the encouraging possibility of key metabolites for empowering cancer immunotherapy.

The function and regulation of TET2 in innate immunity and inflammation.

TET2, a member of ten-eleven translocation (TET) family as α-ketoglutarate- and Fe-dependent dioxygenase catalyzing the iterative oxidation of 5-methylcytosine (5mC), has been widely recognized to be an important regulator for normal hematopoiesis especially myelopoiesis. Mutation and dysregulation of TET2 contribute to the development of multiple hematological malignancies. Recent studies reveal that TET2 also plays an important role in innate immune homeostasis by promoting DNA demethylation or independent of its enzymatic activity.