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Commonly used opioids for pain management primarily target the mu opioid receptor. However, mu opioid receptor agonists often come with harmful side effects. Here, the authors report the results of two phase 3 trials of HSK21542 (anrikefon), a highly selective activator of peripheral kappa opioid receptor agonists, for postoperative pain treatment following abdominal surgery.

Single-pixel imaging can capture a scene without a direct line of sight to the object but high-quality imaging has proven challenging. Here, by acquiring their Fourier spectrum, Zhang et al. demonstrate indirect, high-quality single-pixel imaging in the presence of noisy environmental illumination.

The performance of n-i-p perovskite-organic tandem solar cells is hampered by non-ideal interconnection layers. This study reports an optimized metal-based interconnection stack featuring high transparency and efficient carrier recombination, achieving 25.34% efficiency and improved stability in tandems.

It is extremely difficult to separate tritium from radioactively contaminated water. Here the authors introduce catalytic hydrogen isotope exchange to water distillation, realizing excellent detritiation performance.

Gestational diabetes milletus (GDM) may have impairments on offspring health. Here, the authors suggest that the increase of EZH2 is an important reason for the disrupted DNA methylome in oocytes exposed to GDM, which may be associated with the transgenerational inheritance of the metabolic disorders.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Heavy-duty vehicles are responsible for a substantial portion of road emissions from fossil-fuelled vehicles and cause harmful air pollution. Transitioning to electric heavy-duty vehicles would provide substantial health benefits, especially in Black and Hispanic/Latino urban neighbourhoods.

There are pervasive concerns related to fairness, privacy and regulatory compliance in machine learning applications in healthcare, necessitating a reevaluation of dataset creation practices. Mittal et al. examine various computer vision datasets, providing insights to foster responsible AI development.

Here the authors present cyclic peptide-based AND-gated nanosensors to detect concomitant protease activity. These nanosensors improve detection specificity during immune checkpoint blockade therapy compared with off-tumour anti-viral immunity in a mouse model.

Cell-type-resolved spatial proteomics of the skin from patients with toxic epidermal necrolysis reveals that it is driven by JAK/STAT signaling, leading to successful treatment of this potentially fatal condition in patients using JAK inhibitors.

Combined use of multiple siRNAs promises a new path for drug development. Here, the authors demonstrate a multiplexed combinatorial screening of thousands of siRNA formulations through highthroughput single-cell gene silencing, discovering the most effective anti-cancer siRNA cocktail therapeutics.

5-hydroxymethylcytosine, the sixth DNA base, plays a key role in brain aging and Alzheimer’s disease. Here, the authors study over 1000 deceased brains to identify genes with 5-hydroxymethylcytosine alterations linked to Alzheimer’s pathology.

Here, the authors perform a genome-wide association study of the ALPS-index, identifying 17 unique genome-wide significant loci, unraveling mechanisms of brain glymphatic activity and providing insight for its relation to neuropsychiatric phenotypes.

An engineered skin microbe produces a therapeutic molecule that reduces sebum in mice.

Hydroxyl radicals are reactive species capable of water purification and disinfection, although their generation, particularly through renewable approaches, is challenging. Now, low-valent Au on potassium-incorporated carbon nitride has been shown to produce hydroxyl radicals upon solar illumination and to provide high water disinfection rates.

Bilateral grafts of cryopreserved human embryonic stem cell-derived dopaminergic neuron progenitor cells into the putamen of patients with Parkinson’s disease in a phase I clinical trial showed safety, improvements in off-drug motor function and graft survival at 18 months after transplant.

Artificial intelligence (AI) is becoming increasingly relevant to assist with oncology imaging, but diagnosing rare tumours remains challenging. Here, the authors develop an AI approach to detect rare thyroid cancer subtypes by integrating clinical knowledge with image generation based on ultrasound imaging data from large patient cohorts.

Increased atmospheric evaporative demand in recent years has increased drought severity by an average of 40% globally across both dry and wet regions, and the trend is likely to continue under future warming scenarios.

Accurate quantification of bioimaging data is often confounded by uneven illumination (shading) in space and background variation in time. Here the authors present BaSiC, a Fiji plugin solving both issues. It requires fewer input images and is more robust to artefacts than existing shading correction tools.

As cervical tumours become more invasive, levels of episomal human papillomavirus paradoxically tend to decrease. Here the authors identify a network of antiviral and cell cycle genes that is amplified by chromosomal aberrations and promotes cervical tumour progression.

Controlling the propagation of spin currents with opposite polarities in antiferromagnets has remained challenging. Now the frequency of coherently excited spin waves in a haematite-based device is shown to control the sign of the spin current.

Analysis of pre- and post-chemotherapy samples collected from 22 patients with high-risk neuroblastoma using single-nucleus RNA and ATAC sequencing and spatial omics characterizes therapy-related changes in cell composition and the tumor microenvironment.

A meta-analysis using the Burden of Proof method found increased but modest relative risk of cardiometabolic disease and/or colorectal cancer associated with the consumption of processed meat, sugar-sweetened beverages and trans fatty acids.

An interaction between UTX and 53BP1, which occurs in humans but not mice, promotes neurogenic gene expression that underlies neuronal differentiation and cortical development, perhaps providing insight into human-specific neurodevelopment.

Afatinib is a second-generation EGFR tyrosine kinase inhibitor recommended as the first-line treatment for patients with advanced EGFR mutant non-small cell lung cancer (NSCLC). Here the authors report the results of a phase II clinical trial of neoadjuvant afatinib for stage III EGFR mutant NSCLC.

Large three-dimensional images are commonly generated through biological experimentation. Here the authors report software tools for exploration of three-dimensional images along with applications to assist in imaging, microsurgery, visualization and annotation of large image data sets.

The structural modification of inactive materials to effectively engineer active catalysts is very attractive. Here, layered crystalline Pd₃P₂S₈ is transformed by electrochemical lithiation into amorphous Li-incorporated nanodots. This process turns the inert parent material into a highly active and stable hydrogen-evolving catalyst.

Although pyrethrum is used to repel insects for centuries, the underlying mechanism has been enigmatic. Liu et al. found that specific components of pyrethrum mediate repellency by targeting olfactory receptors and/or voltage-gated sodium channels in Aedes aegypti mosquitoes.

Choi et al. show that autophagy is activated in disease-associated microglia in Alzheimer’s disease mouse models, which prevents microglial senescence entry. Blocking microglial autophagy aggravates neuropathology in Alzheimer’s disease mice.

The discovery of high temperature superconductivity in hydrogen-rich compounds stimulates further extensive studies. Here, the authors report superconductivity in pressurized yttrium-hydrogen system with highest predicted T_c among binary compounds.

The molecular characteristics and therapeutic vulnerabilities of TFCP2-rearranged rhabdomyosarcomas (RMS) require further exploration. Here, the authors use multi-omics analyses and functional and mechanistic investigations to characterize TFCP2-rearranged RMS – including cases with FUS/EWSR1-TFCP2 fusions – across two precision oncology programs.

Advances in organoid culture have enabled the modelling of many aspects of organs in vitro, transforming experimental biology. This Review provides a comprehensive overview of the current and emerging liver and pancreas organoid technologies and discusses current limitations and future directions.

The authors observe an exceptional point and the corresponding phase transition in a superconducting non-Hermitian circuit. They find non-reciprocal microwave transmission can be achieved within the broken symmetry phase in the few-photon regime.

Precipitation impacts leaf senescence. Here, the authors use carbon flux and satellite data to demonstrate that reduced precipitation frequency is associated with a faster drought response in trees and show that Earth system models don’t capture the impact of reduced precipitation.

Analysis of 46 newly sequenced or re-sequenced Tausch’s goatgrass (Aegilops tauschii) accessions establishes the origin of the bread wheat (Triticum aestivum) D genome from genetically and geographically discrete Ae. tauschii subpopulations.

The mechanisms allowing early disseminated cancer cells colonize other tissues remain largely unknown. Here, authors show that GPRC5A axis drives esophageal squamous cell carcinoma lung seeding and metastasis, in a mechanism resembling trophoblast behavior during embryo implantation.

Engineering non-natural functions into enzymes has opened unexpected avenues for chemical synthesis. Whereas past efforts in repurposing natural enzymes have predominantly focused on heme- and flavin-dependent enzymes, latest work further highlights the advantages and potential of non-heme iron enzymes for organic synthesis.

Climate warming causes earlier spring phenological events and higher risk of late spring frost damage. Here, the authors investigate the impact of late spring frosts on phenological events, finding that they delayed flowering by an average of 6 days across 640 species.

Precise control is essential for effective neuromodulation. Here, the authors present an evoked compound action potential-based control system and demonstrate its efficacy in tibial nerve stimulation compared to empirical methods, offering a foundation for quantitative closed-loop control

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Microglia show remarkable regenerative capacity after acute depletion, which had been thought to be derived from de novo progenitors. Peng and colleagues demonstrate that the newly formed microglia are actually solely derived from residual microglia.