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The role of mosquito saliva proteins in viral infection remains incompletely understood. Here, the authors show that sialokinin facilitates viral dissemination while suppressing immune response and inflammation in chikungunya virus-infected mice.

Chen et al. identify a brain-to-bone communication axis whereby extracellular vesicles from aged brain neurons transport WDFY1 protein to distal bone, driving bone-fat imbalance and promoting osteoporosis.

Novel short-acting IL-22 bispecific biologics offer new hope for treating metabolic dysfunction-associated steatohepatitis (MASH), a global health concern with few treatment options. Here, the authors show these drugs significantly improve blood sugar control, liver fat, inflammation, and scarring.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

Tagging tumour cells with microbial antigens using a tumour-specific replicating virus activates memory T cells for treating solid tumours in mouse models.

Precise and scalable regulation of gene expression in mammalian cells is challenging. Here, the authors created a highly tunable CRISPR-based synthetic transcription system for programmable control of mammalian gene expression and cellular activity.

Coagonism, the ability of nonstimulatory antigens to promote T-cell activation, has been reported in mice. Here the authors show that coagonism also occurs in human CD8 T cells, in which a nonstimulatory HIV GAG peptide enhances a specific T-cell response to a hepatitis B virus epitope by amplifying T-cell receptor signals.

Pharmacological inhibition of the prolyl isomerase PIN1, highly expressed in cancer cells and cancer associated fibroblasts (CAF), has been proposed for cancer therapy. Here the authors report the design of a DNA-barcoded micellular system functionalized with antibodies targeting CAFs and a T cell recruiting aptamer to deliver the PIN1 inhibitor AG17724, showing antitumor response in preclinical models of pancreatic cancer.

Responses to SARS-CoV-2 vaccines in different populations are important to define efficacy. Here the authors show using a cohort in Singapore that two doses of mRNA vaccine is less effective in recipients over 60 years of age and that a further dose of vaccine can improve these antibody levels.

Psoriasis is a skin disease associated with neurogenic inflammation. Here, the authors activation of ASIC3 on sensory neurons that leads to the release of CGRP, which triggers inflammation through dendritic cells and drives psoriatic inflammation.

Vaccines for SARS-CoV-2 are needed to fight the pandemic. Here the authors show immunogenicity of an adjuvanted subunit vaccine, SARS-CoV-2 spike protein trimerized with trimer-tag technology, in small animal models and protection from SARS-CoV-2 challenge in non-human primates.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Synovitis is a key early driver of osteoarthritis (OA), and RANKL contributes to cartilage degradation in OA. Here the authors show that denosumab, an anti-RNKL antibody, reduces synovitis and delays OA progression in animal models and patients.

Interstitial macrophages (IM) are a specialised population of macrophage cells in the lungs which regulate lung inflammation. Here using mouse models, the authors show that a CD39⁺CD9⁺ IM population reduce IL-23/Th17 driven neutrophilic inflammation through suppression of NETosis.

DNA damage response inhibitors are a promising cancer therapy. Here, the authors show that combined PARP and ATR inhibition triggers ZBP1-dependent PANoptosis in cancer and normal cells, revealing a mechanism to balance efficacy and toxicity in DDR inhibitor therapies.

Two subclasses of ligand-gated ion channels (ASIC3 and P2X3) are both present at sensory neurons and might be therefore subject to receptor crosstalk. Here authors use electrophysiology, biochemistry and co-immunoprecipitation to show that the two ion channels interact and affect P2X3 currents.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The authors present Gemini, their bifunctional replicon platform capable of functioning as either self-amplifying RNA (saRNA) or self-amplifying DNA (saDNA).

SUMOylation is a post translational modification. Here the authors show that TRPV1, which conveys thermal nociception, is SUMOylated in DRGs in inflammatory conditions and contributes to pain behavior in mice.

How SARS-CoV-2 enters cells and causes COVID-19 is still under intensive investigation. Here, the authors identify unexpected crosstalk between human coronavirus and filovirus entry and discover pan-inhibitors for these highly pathogenic viruses.

Inflammatory responses determine the pathological course of spinal cord injury. Here, the authors report on pH responsive fibers for triggered release of IL-4 plasmid liposomes and sustained release of nerve growth factor to regulate the immune response and promote nerve regeneration to enhance functional recovery.

SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

The early signalling events that trigger initial T-cell receptor signalling are not clearly defined. Here the authors show that this occurs in two stages, the first between the CD8 coreceptor and CD3 requiring Lck association to CD8, while the second interaction requires binding of major histocompatibility molecules.

The deubiquitinase CYLD regulates a TAK1–JNK pathway and can be targeted to ameliorate nonalcoholic steatohepatitis.

T cell homeostasis requires integration of signals from antigen and cytokine receptors. Gascoigne and colleagues demonstrate that the protein Themis supports signals from low-affinity TCR ligands to maintain normal CD8⁺ cell function.

The chemokine, CXCL4, is proposed to enhance Toll-like receptor (TLR) signaling by facilitating TLR ligand import. Here the authors show that CXCL4 also synergizes with TLR8 to promote the activation of TBK1 and IKKε and induce epigenetic remodeling of relevance inflammatory genes to enhance inflammatory responses in human monocytes.

Here, Tulsian et al. identified the effect of biologically relevant full-length IgG binding on the Spike protein from different SARS-CoV-2 variants to comprehensively understand the mechanisms of antibody evasion, towards the development of better antiviral strategies.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

SFTSV is a novel phlebovirus associated with high fatality, but understanding of pathogenesis is lacking. Here the authors show defective cellular immunity, deficient antibody production and defunct humoral immunity is associated with fatal infection in human cases of infection.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

RNA viral infections trigger an immune response mediated by the formation of aggregates of the MAVS protein. Here the authors show that the mitochondrial protein MARCH5 modulates this response by transferring ubiquitin to MAVS aggregates, thus promoting their proteasomal degradation.

Nanoparticles coated with autoantigenic peptides bound to MHC class II molecules suppress established autoimmune disease by inducing antigen-specific T_R1-like regulatory T cells in mouse and humanized mouse models.