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Visible-light-mediated intramolecular [2+2] cycloaddition of aza-1,6-dienes gives bridged, not fused, heterocycles, in violation of the ‘rule-of-five’, which dictates that five-membered rings are preferentially formed. This method allows a variety of bridged bicyclic scaffolds to be accessed, enabling drug-relevant properties to be readily tuned.

Neoantigen-based adoptive T cell therapies represent a personalized approach for cancer immunotherapy. Here the authors describe NEO-STIM, an ex vivo T cell induction platform to STIMulate peripheral blood T cells to generate responses against tumor NEOantigens.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Therapy to allergy often targets a specific allergen without addressing cross-reactivity. Here the authors develop a consensus, cross-reactive allergen, use mRNA-lipid nanoparticle immunization to induce specific, neutralizing IgG responses, but find no therapeutic effects in mouse allergy models, hinting the need for further optimization prior to translation.

Histological analysis of the human pancreas provides insight into initiation and progression of type 1 diabetes (T1D). Here the authors utilize pancreatic tissue sections across different disease stages and apply whole slide imaging and digital pathology to identify endocrine cell composition, immune cell burden and spatial islet relationships in health and over the course of T1D.

Cue-evoked striatal dopamine release in mice encodes bidirectional trajectory errors, spatially and temporally separated from value coding, reflecting the relationship between the speed and direction of ongoing movement relative to optimal goal trajectories.

For Nature Aging’s fifth anniversary, we acknowledge the essential work that is done by our colleagues, without which Nature Aging’s monthly publication would not be possible. We speak with some of our internal colleagues about the process of making a journal every month. Rebecca Roberts is a production editor at Springer Nature, Mark McGranaghan is a senior sub editor, Lauren Snape is an art editor and Amanda Karmolinski is a senior editorial assistant. In this Q&A, Rebecca, Mark, Lauren and Amanda pull back the curtain and tell us about the various roles that go into putting it all together.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

People living with multiple long-term conditions often experience reduced quality of life, but evidence from Southeast Asia is fragmented. Here the authors show that commonly used tools indicate moderately reduced yet generally good quality of life, highlighting the need for context-sensitive measurement approaches.

Therapies combining chemotherapy and immune checkpoint inhibitors have shown limited efficacy in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Here the authors report the results of a pilot phase 1 trial of neoadjuvant modified Folfirinox plus nivolumab in borderline-resectable PDAC, including safety, efficacy and immunological correlates.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

The SONAR trial showed that the endothelin receptor antagonist atrasentan improves kidney outcomes in patients with type 2 diabetes and chronic kidney disease, though individual responses varied. Here the authors report exploratory analyses of the SONAR trial that identify urinary clusterin as a potential predictor of kidney disease progression and response atrasentan in type 2 diabetes.

KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

In this work, the authors reveal that three non-ribosomal peptides targeting a common protein quality system differentially alter the Mycobacterium tuberculosis proteome, providing new insight into the molecular mechanisms behind their antimycobacterial activity.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

Deep brain stimulation tuned to cue-reactivity within the nucleus accumbens region reduced drug cravings, heralding an evocation-based programming strategy for opioid use disorder.

Kornfeld-Sylla et al reveal how alpha brainwaves are altered in children and adults with Fragile X Syndrome (FXS) and find parallel changes in alpha-like rhythms in juvenile and adult FXS model mice, showing their use for testing potential therapies.

Doxycycline has been recommended as post-exposure prophylaxis for prevention of bacterial sexually-transmitted diseases. Here, the authors use mathematical modelling to investigate the potential disease, antimicrobial resistance, and economic implications of this intervention in gay, bisexual, and other men who have sex with men in Australia.

TREM2 is an important AD risk factor playing essential roles in the microglial response to amyloid pathology. Here, authors show using a TREM2 reporter mouse that TREM2 levels are critical for efficacy of TREM2 agonism informing current clinical efforts.

This work demonstrates the first miniature RF filter combining ultrawide tunability (4–18 GHz) and high nonreciprocity, achieving low loss, zero static power, and compact size (1 cc).

This study shows that CrSBr hosts Frenkel-like and Wannier-Mott-like excitons whose distinct spatial character explains their contrasting sensitivity to magnetic order and lattice vibrations, challenging the standard dichotomy in describing excitons.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

A wearable that continuously measures the concentration of a drug is demonstrated in humans.

The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

The Ocean Equity Index provides a systematic, twelve-criteria framework to assess and improve equity in ocean initiatives, projects and policies, producing structured data that guide evidence-based decisions and support more equitable outcomes for coastal communities and ecosystems.

Accurate determination of population size for highly-mobile marine animals is often prohibitively difficult. Here, Bravingtonet al.estimate the abundance of southern bluefin tuna using a method based on the number of parent-offspring pairs detected genetically in samples from the catch.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Hepatic glycogenolysis is essential for protein glycosylation and rhythmic secretion by the liver. Disruptions to hepatic glycogenolysis, caused by congenital diseases or physiological factors such as obesity, caloric restriction and changes to meal timing, alter hepatic protein secretion.

Cosgun et al. show that, in B cell leukemia, β-catenin expression is maintained at low levels through glycogen synthase kinase 3B (GSK3β)-mediated phosphorylation. Inhibition of GSK3β results in β-catenin–Ikaros–NuRD complex formation, leading to B-ALL cell death through MYC repression.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

A national classification system of wetland hydrologic connectivity to streams, which could be applied globally, demonstrates and advances current understanding of how wetland connectivity affects surface water quality.

Climate limits where insects can live and which species can coexist. Using thermal tolerances of 653 moths on Asian mountains, this study shows warmer temperatures broaden thermal tolerance traits diversity; daily variation has little influence, and strong seasonality mildly weakens this pattern.

The properties of electronic transport through edge states of three-dimensional quantum Hall-like states are not yet resolved. Now, increasing the surface area of the edges is shown to produce increased conductance, suggesting that chiral surface states are present.

The authors use data on the entire Finnish population to develop a machine learning model for predicting COVID-19 vaccination uptake. Important predictors are proxies of socio-economic status, and those at high risk for COVID-19 consequences are less likely to get vaccinated.

The hydraulic response time of aquifers with similar residence times varies widely across the globe. Water levels in some aquifers containing fossil groundwater can be controlled by modern climates, according to an analysis of 31 major aquifers.

Media representations depict cities in illuminating ways. This study finds that representations of cities in Soviet-era newsreels grow more than expected with city size and are further biased in favor of some specializations and geographical locations.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

Compiling data on floral introductions and European colonial history of regions worldwide, the authors find that compositional similarity of floras is higher than expected among regions once occupied by the same empire and similarity increases with the length of time the region was occupied by that empire.

Calcium imaging of mouse hippocampal neurons while mice learn a reward-based task over several weeks provides insight into the evolution of the hippocampal reward representation during extended periods of experience.

Experimental evidence demonstrates long-distance remote epitaxial interactions of thin films even through thick amorphous carbon buffer layers and shows that these can be induced through dislocations in the substrate.

The authors survey community palaeontological databases, documenting their contributions to science as well as their vulnerabilities, and provide recommendations for the future of open science databases.

Natural genetic variation of photosynthesis is an underexplored resource for plant genetic improvement. Here, the authors find allelic variations of YS1 affect Arabidopsis photosynthesis acclimation using genome-wide association study, reverse genetics, and quantitative complementation approaches.

Lucerastat was well-tolerated, but did not reduce neuropathic pain, abdominal pain, or diarrhea compared with placebo. Lucerastat reduced biomarkers of Fabry Disease at 6 months, and these reductions were maintained at the 18-month interim analysis.

NiPS₃ is a van der Waals antiferromagnetic semiconductor where the exciton formation is strongly influenced by the magnetic ordering. Previous studies have been limited to magneto-optical approaches, but here, Lebedev, Gish and coauthors succeed in making field effect transistors that operate below the Néel temperature and observe an ultranarrow electroluminescence with a high degree of linear polarization.