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The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

New Zealand implemented stringent COVID-19 control measures early after identification of its first case. Here, the authors perform whole genome sequencing of samples taken until 22 May 2020 and find high viral diversity indicative of multiple separate introductions and limited community transmission.

Grune et al. show that hypokalemic mice develop spontaneous ventricular tachycardia after myocardial infarction, and they use this model to dissect the role of immune cells in arrhythmia: neutrophils increase ventricular tachycardia, partly by promoting reactive oxygen species production, whereas efferocytic macrophages play a protective role.

mTORC1 expression is increased during ageing of muscle, and on the other hand, its activation promotes muscle hypertrophy. Here, the authors assess whether mTORC1 has positive or negative effects on ageing, and show that its long-term inhibition preserves muscle mass and function and neuromuscular junction integrity, whereas muscle-specific activation is associated with sarcopenia.

Sajti and colleagues identify TREM2 as a critical factor in myeloid cells in response to hyperoxia-induced lung injury in neonates, finding that TREM2 deficiency protects mice from bronchopulmonary dysplasia.

Here, the authors develop a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine candidate and show induction of neutralization antibody titers in mice that are comparable to titers in convalescent sera of patients.

The anti-aging intervention calorie restriction (CR) is thought to act via the nutrient-sensing multiprotein complex mTORC1. Here the authors show that the mTORC1-inhibitor rapamycin and CR use largely distinct mechanisms to slow mouse muscle aging.

Topical microbicide combined with vaccine effectively prevents infection of female macaques with simian immunodeficiency virus.

A peritumourally implanted macroporous scaffold releasing small molecules and antibodies to suppress regulatory T cells and to attract and stimulate effector T cells enhanced endogenous antitumoural responses in mice bearing aggressive tumours.

In this study, the authors provide a global overview of SARS-CoV-2 genome sequencing, and estimate the proportion of cases sequenced and time to genome upload. They identify disparities and highlight the need to strengthen surveillance in lower and middle income countries.

Antimicrobial resistance has evolved over decades due to widespread antimicrobial use, with resistance genes now circulating across humans, animals and the environment, creating complex cross-sector connectivity challenges. This Perspective advocates for genomics-based studies of AMR connectivity to enable coordinated global action and investment under the One Health framework.

Sepsis induces a period of immunosuppression which can be problematic in the face of subsequent infectious challenge. Here the authors show the presence of PD-L1 expressing regulatory plasma cells that can inhibit T cells in a murine model and in patients with sepsis.

Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone.

In-mold electronics often rely on vacuum forming processes, which are traditionally limited to thermoplastics. Here, the authors introduce a vacuum forming method for thermoset materials using frontal polymerization.

A fluorogenic reporter allows visualization of spike protein and ACE2 receptor interaction and the identification of natural products that inhibit SARS-CoV-2 replication in vitro and in vivo.

Statistical mapping techniques provide insights into the spread of two key arbovirus vectors in Europe and the United States, and predict the future distributions of both mosquitoes in response to accelerating urbanization, connectivity and climate change.

Many genetic variants have been associated with body size, but the contribution of copy number of rDNA is unknown. Here, the authors explore the association between rDNA copy number and body size in both rats and humans, finding that lower rDNA CN is associated with higher weight and BMI.

Despite rapid and significant changes during the pandemic, prognostic models for COVID-19 patients do not currently account for data drifts. Here, the authors develop a framework for continuously monitoring and updating prognostic models and applied it to predict 28-day survival in COVID-19 patients.

To forge a strong climate accord in Paris, nations must agree on a common goal in everyone's self-interest, say David J. C. MacKay and colleagues.

Analysis of SARS-CoV-2 genomes from around the world show that following initial importation largely from India, Delta spread in England was driven first by inter-regional travel and then by local population mixing.

Leveraging data from a longitudinal field experiment, Taylor and colleagues show that identity cues, such as a username, increase how viewers vote and reply to online content. Their results support a rich-get-richer dynamic when identity cues are salient.

Many countries have closed schools as part of their COVID-19 response. Here, the authors model SARS-CoV-2 transmission on a network of schools and households in England, and find that risk of transmission between schools is lower if primary schools are open than if secondary schools are open.

Rapid antigen tests and syndromic surveillance for identification of COVID-19 cases are limited by low sensitivity and specificity, respectively. Here, the authors use data from Bangladesh and show that combining the two methods improves diagnostic accuracy in a range of epidemiological scenarios.

The antibody response of children to SARS-CoV-2 is less well studied than in adults. Here Hachim et al. show that children have reduced antibody levels to structural proteins and suggest that the predominance of antibody responses to non-structural proteins can be used to discriminate infection and vaccination.

An online training module that synergistically targets two different mindsets can reduce stress levels in adolescents in the context of social-evaluative stressors—stressful experiences in which individuals fear that others are judging them negatively.

A 3D-printed lab-on-a-chip allows for the concurrent rapid electrochemical detection of SARS-CoV-2 RNA in saliva and of anti-SARS-CoV-2 antibodies in saliva spiked with blood plasma.

Aerial and underwater survey data combined with satellite-derived measurements of sea surface temperature over the past two decades show that multiple mass-bleaching events have expanded to encompass virtually all of the Great Barrier Reef.

An assessment of fish movement along stream networks of the southern Appalachian Mountains identifies species-intrinsic sensitivities and habitat characteristics that allow some fish to disperse to keep pace with climate change but prevent successful climate tracking in some species.

The risks to human well-being of floods in the United States have long been overlooked and underestimated, particularly for low-income and marginalized communities. In Los Angeles, flood risks are disproportionately high for historically disadvantaged populations and communities already facing social inequities.

There is limited data on drug resistance in South African communities strongly affected by HIV. In this study, the authors observed low levels of resistance to newer drugs but widespread resistance to older HIV medications in a South African community. Resistance to rilpivirine was detected even in untreated individuals.

The authors determined crystal structures of the main protease (Mpro) of SARS-CoV-2 bound to substrate peptides. These structures define the substrate envelope and enable identification of sites that may be susceptible to drug resistance.

Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.

Extracellular vesicles (EVs), a diverse range of membrane-delimited particles, have multiple cellular functions and, when released by cancer cells, can promote tumour growth and metastatic dissemination. The authors of this Review describe advances in the development of EVs as biomarkers and cancer therapeutics, focusing on clinical translation of EVs into diagnostic and therapeutic clinical tools.

While reflective pavement has been proposed and applied in pilot projects, its actual cooling performance remains unclear. Here, authors assessed the cooling potential of reflective pavement in Phoenix, AZ, using multiple heat metrics, reflectivity measures, and literature to provide a set of implementation guidelines.

A detailed assessment of the techno-economic potential of enhanced rock weathering on croplands identifies national CO₂ removal potentials, costs and engineering challenges if it were to be scaled up to help meet ambitious global CO₂ removal targets.

IL-10 exerts its anti-inflammatory activity in macrophages by increasing the expression of enzymes that promote fatty acid desaturation and downstream regulation of the transcription factor REL.

Whilst estrogen is known to be tumorigenic in some breast cancer, in some contexts it can be protective against invasion and dissemination. Here, the authors show estrogen can promote generation of Suppressive Cortical Actin Bundles that can inhibit motility dynamics through EVL-mediated actin cytoskeletal remodeling.

Tropical diseases, such as malaria, can develop resistance to specific drugs. Godinez and colleagues present here a generative design approach to find new anti-malarial drugs to circumvent this resistance.

By conducting a large multi-ancestry GWAS of varicose veins followed by bioinformatics analyses, Levin et al. identified new and recurrent causal variants, traits with shared genetic mechanisms, and putative causal risk factors of the disease, revealing its polygenic architecture and genetic overlap with arterial and venous disease and identifying potential therapeutic targets.

Benzoxaboroles have been shown to be active against different pathogens. Here, the authors show that the benzoxaborole AN3661 inhibitsPlasmodium falciparum in vitroand in mouse models, and identify a homologue of a mammalian cleavage and polyadenylation specificity factor as a drug target.

Expansion of rubber plantations threatens tropical forest carbon stocks and biodiversity, but may be dis-incentivised using carbon finance. Here, Warren-Thomas et al. use forest and agricultural data for Cambodia to show that carbon prices of $30–$51 per tCO₂ are needed to match forest protection costs.