Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.

Stimulator of interferon genes (STING) traffics across intracellular compartments to trigger innate responses. Mutations in factors regulating this process lead to inflammatory disorders. To systematically identify factors involved in STING trafficking, we performed a genome-wide optical pooled screen (OPS).

Design of high specificity binders for peptide-MHC-I complexes.

Class I MHC molecules present peptides derived from intracellular antigens on the cell surface for immune surveillance, and specific targeting of these peptide-MHC (pMHC) complexes could have considerable utility for treating diseases. Such targeting is challenging as it requires readout of the few outward facing peptide antigen residues and the avoidance of extensive contacts with the MHC carrier which is present on almost all cells. Here we describe the use of deep learning-based protein design tools to design small proteins that arc above the peptide binding groove of pMHC complexes and make extensive contacts with the peptide.

Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.

STING is an innate immune sensor that traffics across many cellular compartments to carry out its function of detecting cyclic di-nucleotides and triggering defense processes. Mutations in factors that regulate this process are often linked to STING-dependent human inflammatory disorders. To systematically identify factors involved in STING trafficking, we performed a genome-wide optical pooled screen and examined the impact of genetic perturbations on intracellular STING localization.

Protons are the new first responders.

Human STING's newfound function as a channel expands our understanding of immunity.

Human STING is a proton channel.

Proton leakage from organelles is a common signal for noncanonical light chain 3B (LC3B) lipidation and inflammasome activation, processes induced upon stimulator of interferon genes (STING) activation. On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport.

Exposure of iPSC-derived human microglia to brain substrates enables the generation and manipulation of diverse transcriptional states in vitro.

Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer's disease. These cells adopt distinct transcriptional subtypes known as states. Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells.

ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling.

Stimulator of interferon genes (STING) is an intracellular sensor of cyclic di-nucleotides involved in the innate immune response against pathogen- or self-derived DNA. STING trafficking is tightly linked to its function, and its dysregulation can lead to disease. Here, we systematically characterize genes regulating STING trafficking and examine their impact on STING-mediated responses.

Dopamine Hydrochloride-Assisted Synergistic Modulation of Perovskite Crystallization and Sn Oxidation for Efficient and Stable Lead-free Solar Cells.

Tin perovskites have received great concern in solar cell research owing to their favorable optoelectronic performance and environmental friendliness. However, due to their poor crystallization and easy oxidation, the performance improvement for tin-based perovskite solar cells (TPSCs) is rather challenging. Herein, reductive 3-hydroxytyramine hydrochloride (DACl) with NH·HCl and phenol groups as co-additives with SnF is added into the precursor to modulate perovskite crystallization and inhibit Sn oxidation for high-performance TPSCs.

Platinum Cluster/Carbon Quantum Dots Derived Graphene Heterostructured Carbon Nanofibers for Efficient and Durable Solar-Driven Electrochemical Hydrogen Evolution.

Large scale solar-driven hydrogen production is a crucial step toward decarbonizing society. However, the solar-to-hydrogen (STH) conversion efficiency, long-term stability, and cost-effectiveness in hydrogen evolution reaction (HER) still need to be improved. Herein, an efficient approach is demonstrated to produce low-dimensional Pt/graphene-carbon nanofibers (CNFs)-based heterostructures for bias-free, highly efficient, and durable HER.

Surface chemistry in calcium capped carbon quantum dots.

Colloidal carbon quantum dots (C-dots) have attracted a lot of attention because of their excellent optical properties for various types of applications. Due to the complicated structure of C-dots, the photoluminescence (PL) mechanism of C-dots is still unclear. In particular, it is still a big challenge to understand well the surface chemistry of C-dots.

Value of anal swabs for SARS-COV-2 detection: a literature review.

Facing the unprecedented global public health crisis caused by coronavirus disease 2019 (COVID-19), nucleic acid tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the gold standard for diagnosing COVID-19. The asymptomatic carriers were not suspected of playing a significant role in the ongoing pandemic, and universal nucleic acid screening in close contacts of confirmed cases and asymptomatic carriers has been carried out in many medium- and high-risk areas for the spread of the virus. Recently, anal swabs for key population screening have been shown to not only reduce missed diagnoses but also facilitate the traceability of infectious sources.

Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.

The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines.