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Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

Neuroinflammation triggers DNA damage and subsequent parthanatos-mediated neuron death. Inhibiting parthanatos in a mouse model of autoimmune inflammation is neuroprotective and reduces disease-associated paralysis.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

New antimalarials are urgently needed. Here, the authors identify Open Source Malaria compound, OSMS-106, as a reaction hijacking inhibitor of the malaria parasite protein synthesis machinery, with potential use for treatment and prophylaxis.

Ciofani and colleagues identify the transcription factor c-Maf as a universal regulator of the differentiation of IL-17-producing γδ T cells.

A machine-learning-based computational approach to probe pathway coessentiality reveals that complex II of the electron transport chain regulates de novo purine synthesis, and can be targeted to treat acute myeloid leukaemia.

Patients with partial recombination-activating gene (RAG) deficiency (pRD) present variable late-onset autoimmune clinical phenotypes. Walter and colleagues identified a restricted primary B cell antigen receptor repertoire enriched for autoreactivity and clonal persistence in pRD. They described dysregulated B cell maturation with expansion of T-bet⁺ B cells revealing how RAG impacts stringency of tolerance and B cell fate in the periphery.

A combination of fluorescent antibodies is used to build visual maps of all myeloid cells in the bone marrow, providing new insight into how the bone marrow microenvironment regulates cell-fate decisions.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

Hot carriers in perovskites experience slow cooling.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Self-ordered heterogeneous nanostructures are of broad interest for both fundamental studies and technological applications. Here authors show that segregation in a multicomponent system during growth can yield highly strained germanium nanowire arrays embedded within a ternary semiconductor matrix.

A study describing an approach that combines imaging and profiling techniques to structurally and functionally analyse lung cancer in vivo, revealing heterogeneous mitochondrial networks and an association between bioenergetic phenotypes and mitochondrial organization and function.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Ronchese and colleagues show that IL-13 secreted homeostatically by dermal ILCs contributes to the differentiation of a CD11b^lo type 2 dendritic cell subset, which supports the development of T_H2 cells and curtails the development of T_H17 cells in the skin of mice and humans.

Under extreme conditions, nonlinear lattice dynamics in a material can manifest and reveal unexpected properties. Here, using inelastic neutron scattering and first-principles calculations the authors find the presence of nonlinear travelling waves in a fluorite structured system, which exhibit characteristics different from regular phonons.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Bcl-6 is the signature transcription factor for T_FH cells. Crotty and colleagues provide a comprehensive transcriptional map depicting the regulatory circuitry controlled by Bcl-6 in determining T_FH cell fate and function.

Eosinophils exist as a functionally heterogeneous population. Whether the heterogeneity is driven by cell-intrinsic or extrinsic factors is underexplored. Here, by leveraging single-cell transcriptomic data and epigenomic analysis, the authors propose that local environmental cues define the gene expression program of murine esophageal eosinophils and identify AP-1 family members, including ATF3, as key regulators of gene expression.

Experimental evidence for charge coupling to ferroelectric soft mode is scarce. Here, the authors find a photogenerated coherent phonon coupling to the electronic transition above the bandgap in the van der Waals ferroelectric semiconductor NbOI2.

An epsilon-near-zero medium is used to demonstrate ultrastrong coupling between phonons and gap plasmons. The approach may pave the path to exploitation of vibrational transitions.

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.

Vaccines inducing mucosal immunity may provide better protection from respiratory viruses. Here, Ykema et al. demonstrate the utility of a bivalent, mucosally delivered nanostructured lipid carrier-replicon vaccine for induction of mucosal and systemic immunity and protection against morbidity and mortality from H5N1 and H7N9 influenza.

In non-small cell lung cancer, the presence of monocyte-derived macrophages inversely correlates with the presence of NK cells. Merad and colleagues propose that when monocytes phagocytose tumor debris they express TREM2, become pro-tumorigenic, and suppress NK cell recruitment and activation in tumors.

Bispecific CAR T cells targeting CD19 and CD22 exhibit clinical activity and low toxicity in patients with large B cell lymphoma and B cell acute lymphoblastic leukemia, with relapses associated with loss of CD19 but not CD22.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

This study found E. coli phylogenetic background shapes TEM-1 beta-lactamase expression and co-amoxiclav resistance. Phylogeny alone shifted isolates from susceptible to resistant, stressing a need for lineage-sensitive genotype-phenotype prediction.

Invariant natural killer T (iNKT) cells populate barrier surfaces during an early-life window. Blumberg and colleagues demonstrate that such barrier surface iNKT cells develop via an extrathymic pathway dependent on a specialized population of embryo-derived macrophages.

Arthritis is the most common rheumatic immune-related adverse event (irAE) occurring in cancer patients receiving immune checkpoint inhibitors. Here the authors study the immune landscape of blood and synovial fluid samples from patients with arthritis-irAE, reporting immunological differences and similarities with classic autoimmune arthritis.

Researchers experimentally demonstrate a fully integrated coherent optical neural network. The system, with six neurons and three layers, operates with a latency of 410 ps.

Lung adenocarcinomas frequently harbour KRAS mutations, of which a subset are characterized by co-mutation of KEAP1. Here the authors show, in mice, that Kras^G12D mutant tumours are metabolically distinct, with a bronchiolar cell-of-origin.

Lipid metabolism regulates stem cell states and differentiation. Here, the authors demonstrate a requirement in planarians for Apolipoprotein B-mediated neutral lipid transport from intestinal stores to stem cells and their progeny during differentiation and whole-body regeneration.

The team of authors led by Seon-Kyeong Jang use whole-genome sequencing data and show that rare genetic variants explain much of the ‘missing heritability’ in smoking behaviours. These results help address a long-standing mystery in behavioural genetics.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Metabolites in the tumor microenvironment, including adenosine, have been shown to suppress anti-tumor immune responses. Here, the authors show that T cell expression of the adenosine transporter ENT1 is involved in this immunosuppression and can be targeted to boost T cell function, tumor killing and immune checkpoint blockade.

Conventional solid-state electrolyte design is limited by dopant–lattice compatibility. This work introduces solid dissociation, using halide van der Waals materials to dissolve salts and create amorphous conductors with high ionic conductivity and potential for use in devices.

Sanz and colleagues examine B cell subsets in a cohort of patients with COVID-19. Severely ill patients have higher frequencies of activated extrafollicular T-bet⁺ B cells that form antibody-secreting cells, the majority of which express germline sequences and are reminiscent of antibody responses observed in patients with systemic lupus erythematosus during flares.

TRIM7 acts as an antiviral factor during SARS-CoV-2 infection, by ubiquitinating the M protein on K14 and inhibiting caspase-6-dependent apoptosis. The natural K14 mutations in circulating strains support the physiological role of M ubiquitination.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Mitochondrial aspartate regulates ER morphology and co-translational translocation via BiP ADP ribosylation. In T cells from patients with rheumatoid arthritis, mitochondrial aspartate is deficient, resulting in ER expansion and excessive production of the pro-inflammatory cytokine TNF.

Colonna and colleagues show that the clock genes encoding REV-ERBα and REV-ERBβ maintain ILC3 functions in the gut by controlling the expression of RORγt.