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Cytokine-induced signaling acts as an ON/OFF switch dependent on the presence of ligands. Here the authors construct synthetic cytokine receptors responsive to synthetic ligands able to activate canonical signaling pathways.

Two-dimensional fluid interfaces are ubiquitous, but studying their surface dynamic properties is difficult because of coupling between the film and bulk fluid. Choiet al.combine active microrheology with fluorescence microscopy to image fluid interfaces under applied stress.

Induced motion has emerged as a method to increase the efficacy of delivery and therapeutic outcomes using nanomaterials. Here, the authors report on a Janus gold shell polymersome with aggregation-induced emission molecules for phototactic and photodynamic therapy applications.

The suite of small moons orbiting close to Saturn exhibits a variety of shapes that provide clues to moon formation processes. A model shows that all of these shapes can be obtained with a single mechanism: merging collisions among similar-sized moonlets.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

The Fair Human-Centric Image Benchmark (FHIBE, pronounced ‘Feebee’)—an image dataset that implements best practices for consent, privacy, compensation, safety, diversity and utility—can be used responsibly as a fairness evaluation dataset for many human-centric computer vision applications.

The dTAG system pairs potent heterobifunctional degraders and extensible tagging strategies to achieve immediate and reversible degradation of divergent proteins, facilitating biological investigation and drug target validation in cells and in mice.

Here the authors develop a coacervate micromotor that can display autonomous motion as a result of stochastic distribution of propelling units. This stochastic-induced mobility is validated and explained through experiments and theory.

Kaposi’s sarcoma-associated herpesvirus changes mitochondrial architecture via vBcl-2 interaction with a host NDP kinase, which triggers mitochondrial fission and inhibition of MAVS allowing for virus production.

The synthesis of well-defined heterostructure interfaces can be leveraged to design advanced catalysts. Now a catalyst consisting of carbon-supported Janus particles with crystalline Ru and amorphous CrO_x sides is shown to achieve high performance for both alkaline hydrogen oxidation and evolution reactions due to the synergy between both sides.

Therapeutic modulation of Janus kinase family enzymes is an established approach for inflammatory and autoimmune skin diseases. Here the authors rationally design small interfering RNAs to enable single Janus kinase targeting and test this new therapeutic approach in a skin disease model for maintaining efficacy and improving selectivity.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

Microrobot collectives promise new functions beyond individuals’ capability. Here, nature-inspired reconfigurable self-assembly of microrobots was created, driven by their photocatalytic and magnetic properties, showing potential application in water purification.

A subset of antigen-presenting cells of myeloid origin that require PRDM16 and RORγt regulates T cell function to enable immune tolerance of food and commensal gut microorganisms.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

LKB1-mut has been shown as a major genetic driver of primary resistance to immune checkpoint inhibitors. Here this group reports the identification of the LKB1-IAP-JAK dynamic complex as a molecular determinant for immune response of LKB1-mut lung cancer cells.

Anti-TNF CAR macrophages show anti-inflammatory efficacy in both acute and chronic inflammatory disease mouse models.

Understanding patient-specific pathobiological pathways is a critical step for advancing precision medicine. Here the authors show that individualized protein-protein interaction networks provide key insight on patient-level pathobiology and clinically relevant pathophenotypic characteristics in a complex disease.

This multi-ancestral meta-analysis of alcohol use disorder in over one million individuals identifies genome-wide significant risk variants from independent genomic loci and shared genetic architecture between alcohol use disorder and other mental and general medical conditions.

Inositol pyrophosphates (PP-IPs) regulate immunity and phosphate homeostasis. Here, the authors’ structural dissection of an Arabidopsis thaliana PP-IP phosphatase reveals that substrates drive their own hydrolysis and identifies a highly elusive metaphosphate-like reaction intermediate.

This Review highlights the current potential for colloidal quantum dots for applications in quantum sensing and quantum circuits.

Solution-based syntheses of nanoclusters typically produce a broad range of species. A step-by-step process using DNA-encoded nanoparticles assembled on a solid support aids in the design and production of specific self-assembled nanoclusters in high yields.

Coactivator-associated arginine methyltransferase 1 (CARM1) is an important target in hematologic malignancies. In this work, the authors show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates CARM1 which regulates its methyltransferase activity and alters its target specificity.

In a randomized phase 3 trial, the combination of the BET inhibitor pelabresib with the JAK inhibitor ruxolitinib resulted in a significantly higher spleen volume reduction from baseline versus placebo with ruxolitinib in patients with JAK inhibitor-naive myelofibrosis.

Trefoil factor 1 (TFF1) is a protein secreted by the gastric mucosa that protects against gastric tumourigenesis. Here, the authors show that TFF1 inhibits the oncogenic inflammatory response and IL-6-mediated STAT3 activation by interfering with the binding of IL6 to its receptor IL6Rα.

Immune function decreases with age, leading to increased risk of infectious disease. The authors show that N-glycan branching increases with age in females more than in males as a result of a sex-dimorphic increase in N-acetylglucosamine and interleukin-7 signaling. Reversing elevated branching reduced infection severity in aged female mice.

SOCS2 is a key regulator of growth hormone and cytokine signaling, which recognizes phosphotyrosine (pTyr)-modified targets via a central SH2 domain. Here, the authors discover and characterize an exosite on this SH2 domain that can bind a non-phosphorylated peptide to enhance SOCS2:pTyr affinity.

Colloid science has developed through innovative use of silane coupling agents. We highlight the advances in complex colloid synthesis, focussing on 3-trimethoxysilylpropyl methacrylate (TPM) and related compounds. We outline the remarkable properties, unique synthesis strategies and ensuing pioneering applications of TPM colloids.

Current first-line treatments of pediatric UC maintain a 6-month remission in only half of the patients. Here, applying multi-omics on intestinal biopsies from treatment-naïve children, the authors show that relapse-prediction using separate omics data is outperformed by a robust machine learning approach combining microbiomes and epigenomes.

Intense lasers enable scientists to study the behaviour of matter under extreme pressures, but obtaining information about its atomic structure is challenging. In this work, Suggit et al. demonstrate the use of white-light X-ray diffraction to probe the structure of laser-shocked copper on nanosecond timescales.

Janus kinases (JAKs) are essential signalling mediators downstream of many pro-inflammatory cytokines. Jakinibs — small-molecule inhibitors of JAKs — have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies. This Review discusses the biology, development and efficacy of jakinibs in the treatment of immune and inflammatory diseases.

A supramolecular system has been assembled that moves autonomously in the presence of a molecular fuel. Platinum nanoparticles entrapped in a polymer stomatocyte — a bowl-shaped polymer vesicle — catalyse the decomposition of the molecular fuel, hydrogen peroxide. The resulting generation of water and oxygen induces a directional movement of the stomatocyte.

Zanin, Viaris de Lesegno et al. identify what controls the endosomal activation of the IFNAR receptor by IFN-α and establish a central role for endosomal sorting via STAM and Hrs in the differential regulation of JAK–STAT signalling by IFN-α and IFN-β.

The OX₂ orexin receptor (OX₂R) is a brain GPCR that regulates wakefulness and circadian rhythms in humans, and a potential drug target in insomnia and narcolepsy. Here, the authors use cryo-EM to determine how the first clinically tested OX₂R agonist TAK-925 can activate OX₂R in a selective manner.

Reductive aminases show strong potential for the sustainable synthesis of chiral amines, but their application in industrial scale processes is lacking. Now, such an enzyme is screened and engineered allowing its use in commercial manufacturing of abrocitinib JAK1 inhibitor in multi-metric tons.

Membrane-free synthetic DNA-based condensates enable programmable control of dynamic behaviors as shown by phase-separated condensates in biological cells. Here, the authors demonstrate remote-controlled microflow using photocontrollable state transitions of DNA condensates, using an azobenzene motif.

A highly selective inhibitor of the DCLK1/2 kinases is used to uncover the consequences of DCLK1 inhibition on viability, phosphosignaling and the transcriptome in patient-derived organoid models of pancreatic ductal adenocarcinoma.

A genome-wide collection of N-terminally tagged yeast libraries allows easy swapping of tags and exploration of the yeast proteome.