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μ opioid receptors (MORs) expressed on primary afferent nociceptor neurons are responsible for two maladaptive side-effects of chronic opioid use: opioid tolerance and opioid-induced hyperalgesia (pain). A combination therapy of opioid receptor agonism plus peripheral-restricted MOR antagonism abrogates these side-effects while preserving opioid analgesia in rodent models of peri-operative and chronic pain.

Bacterial endospores are among the most resilient forms of life. Here, authors reveal ultrastructural details of the spore chromosome and the multiprotein, multilayered extracellular coat, shedding light on mechanisms contributing to spore resistance.

Desmoplastic Small Round Cell Tumor (DSRCT) is an aggressive malignancy characterized by EWS-WT1 fusion oncoproteins with limited mechanistic understanding. Here, the authors identify EWS-WT1-dependent gene regulation networks and target genes, as well as the activities of two EWS-WT1 isoforms with distinct DNA binding profiles, both of which are indispensable for DSRCT formation.

The function of TRPA1 channels in the mammalian cochlea is poorly understood. Here, the authors show that TRPA1 channels in supporting cells of the organ of Corti mediate contractile responses that may contribute to temporary shifts in hearing thresholds after noise exposure in mice.

Host cell recognition is mediated by the phage tail tip proteins, which then triggers viral genome delivery via the phage tail. Here, the authors combine crystallography and cryoEM to structurally characterise the bacteriophage T5 tail tube structure before and after interaction with its host receptor.

It is unclear whether tropical forest fragments within plantation landscapes are resilient to drought. Here the authors analyse LiDAR and ground-based data from the 2015-16 El Niño event across a logging intensity gradient in Borneo. Although regenerating forests continued to grow, canopy height near oil palm plantations decreased, and a strong edge effect extended up to at least 300 m away.

Rapid insertion and extraction of lithium ions from a cathode material is imperative for lithium-ion battery function. Here, the authors present evidence of inhomogeneities in charge localization, local structural distortions and polaron formation induced upon lithiation using scanning transmission X-ray microscopy.

This study presents an approach to deal with spatial, temporal and phylogenetic non-independence in large-scale analyses of biodiversity change, improving trend estimation and inference across scales.

Macroscopic single crystals with controlled texture are formed from a self-assembled columnar discotic liquid crystal.

Experimental demonstrations of materials supporting electron fluids have been elusive so far. Here, the authors investigate nonlocal transport in bilayer graphene across the ballistic-to-hydrodynamic crossover, and identify a sharp maximum of negative resistance at the transition between the two regimes.

Resequencing analyses of three species of wild sunflower identify large non-recombining haplotype blocks that correlate with ecologically relevant traits, soil and climate characteristics, and that differentiate species ecotypes.

Moderate heat stimulates the growth of Arabidopsis shoots in an auxin-dependent manner. Here, Martins et al. show that elevated ambient temperature modifies root growth by reducing the BRI1 brassinosteroid-receptor protein level and downregulating brassinosteroid signaling.

Tighanimine et al. perform integrative time-resolved transcriptome and metabolome analysis in senescent cells and find that glycerol-3-phosphate and phosphoethanolamine accumulate and rewire lipid metabolism to promote senescence.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

β-cell dysfunction in diabetes is caused by glucose and inflammation toxicity. Here, Fu et al. show that β-cell glucose metabolism can be protective though pyruvate carboxylase–mediated shunting of arginine to ureagenesis and away from toxic nitric oxide production, thus suppressing inflammation.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

Combined analysis of new genomic data from 116 ancient hunter-gatherer individuals together with previously published data provides insights into the genetic structure and demographic shifts of west Eurasian forager populations over a period of 30,000 years.

A high-throughput assay that introduces mismatched base pairs into the DNA sequence shows that mismatches can increase transcription factor binding affinity by prepaying some of the energetic cost of distorting the DNA.

The glucagon-like peptide-1 receptor (GLP-1R) can be targeted in the treatment of diabetes, obesity and other metabolic disorders. Here, the authors assess the molecular mechanisms of peptide agonists binding to GLP-1R and the responses elucidated by these ligands, including distinct kinetics of G protein activation.

Infection of African green monkeys with SIV is associated with reduced pathogenicity. Here the authors explore the requirement of differentiated NK cell populations in a pathogenic Rhesus macaque model of SIV infection and show administration of IL-21 and IFNα rescues terminally differentiated NK cells, similarly to what found in African green monkeys, and limits the SIV reservoir in antiretroviral therapy treated macaques.

The mechanism of oxygen redox in high-energy transition metal oxide cathodes is elusive. Here the authors illustrate the nature of the electron-hole states on oxide ions, offering insights for realizing reversible, high-voltage cathodes.

Understanding the dynamics of ring polymers is challenging are despite recent progress, understanding of the nonequilibrium behavior of ring polymers has not yet been achieved. Here, the authors directly observe the flow dynamics of DNA-based rings in semidilute linear polymer solutions using single molecule techniques.

New fossils from Australia reveal that the Cambrian apex predator Anomalocaris possessed compound eyes more powerful than those of most living arthropods.

A subset of inflammatory group 3 innate lymphoid cells, here termed iILC3s, infiltrate the central nervous system and promote neuroinflammation and disease progression in a mouse model of multiple sclerosis.

Focal adhesions (FAs) initiate chemical and mechanical signals involved in cell polarity, migration, proliferation and differentiation. Here, authors combine single protein tracking, super-resolution microscopy and functional assays, which allow correlating the molecular behaviour and 3D nanoscale localization of kindlin with its function in integrin activation inside FAs.

Sluggish Zn²⁺-dominated Faradic reactions lead to suboptimal charge-storage capacity and durability of aqueous zinc battery cathodes. Here, the authors present a proton-selective interfacial coating strategy that enables high-performance cathodes with fast-kinetics proton-dominated Faradic reactions.

Trencher and colleagues investigate the twenty companies making the largest purchases of offsets from the voluntary carbon market from 2020 to 2023. They find that 87% of the purchased offsets carry a high risk of not providing real and additional emissions reductions. Further, most offsets do not meet industry standards regarding age and country of implementation. The findings reinforce concerns that the voluntary carbon market is failing to support effective climate mitigation.

Though active metasurfaces have been attractive for applications requiring control of optical wavefronts, realizing metasurfaces with full phase control remains a challenge. Here, the authors report a metasurface design strategy for enhanced dynamic phase modulation and tunability.

A laser scanning microscope equipped with quantitative phase imaging is trained with a neural network to perform artificial confocal microscopy

Near-infrared emission at around 2 µm is observed from HgTe nanocrystals. LEDs based on this material platform could prove to be a useful low-cost, convenient light source for applications in gas sensing and other tasks.

The detailed interplay between electronic and lattice dynamics in two-dimensional perovskite materials remains elusive. Here the authors establish the room-temperature polaronic nature of the excitons in two-dimensional Dion–Jacobson-type perovskites.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

It is believed that mutations in desmosomal adhesion complex protein plakophilin 2 (PKP2) cause arrhythmia due to loss of cell-cell communication. Here the authors show that PKP2 controls the expression of proteins involved in calcium cycling in adult mouse hearts, and that lack of PKP2 can cause arrhythmia in a structurally normal heart.

Expression of three Yamanaka transcription factors in mouse retinal ganglion cells restores youthful DNA methylation patterns, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice, suggesting that mammalian tissues retain a record of youthful epigenetic information that can be accessed to improve tissue function.

The authors present two independent reconstructions and a model simulations of Atlantic hurricane activity over the last millennium and show that it is mainly driven by internal climate variability instead of external forcings.

Here, the authors show the amyloid formation of a low-complexity domain of NCAP, and its potential for guiding the design of antiviral agents.

A new interpretation of fossilized soils (palaeosols) suggests that at least some Ediacaran (625–542 million years ago) organisms lived on land; thus these Ediacaran fossils were not animals, but a fungus-dominated terrestrial biota that predated vascular plants by about 100 million years.

The lack of effective drug delivery strategies has impaired the therapeutic progress in the treatment of glioblastoma (GBM). Here, the authors engineer synthetic protein nanoparticle based on polymerized human serum albumin equipped with the cell-penetrating peptide iRGD to deliver siRNA against STAT3 and report improved survival in a mouse model of GBM.