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In this single-arm phase 2 trial in patients with HR⁺HER2⁻ advanced breast cancer, treatment with the HER3-targeting antibody–drug conjugate paritumab deruxtecan led to encouraging objective response rates, and comprehensive exploratory analyses indicate potential biomarkers of response.

The optical properties of nanographenes can be engineered by designing their size, shape, and edges. Here, the authors show that graphene quantum dots are single photon emitters at room temperature, and their emission wavelength can be controlled by edge functionalization.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Green hydrogen production via water electrolysis requires a low-cost solution to provide efficient catalysts. Here, the authors report an industrially scalable method for synthesizing NiFe layered double hydroxide at room temperature and atmospheric pressure, enhancing alkaline electrolysis.

Alkaline ceramidases (ACERs) are a class of poorly understood transmembrane enzymes controlling the homeostasis of ceramides. Here authors solve the Xray structure of human ACER3 and uncover a Ca2+ binding site providing an explanation for the known regulatory role of Ca2+ on ACER3 activity.

The pathophysiology of Amyloid light-chain (AL) amyloidosis remains poorly understood due to the lack of reliable in vivo models. Here, the authors describe a transgenic mouse model that reproduces cardiac AL amyloidosis and provides new information on the formation of AL amyloid fibrils.

Here the authors present the structure of Replication Protein A (RPA) in Archaea. The RPA structure from P. abyssi has been determined in presence and absence of DNA, providing insights into the evolution of this replication factor in eukaryotes

Energy homeostasis requires brain sensing of peripheral metabolic signals. Here, the authors show that energy-state-dependent aggrecan deposits by hypothalamic neurons at a key interface gate brain entry of blood-borne signals and thus food intake.

The capacity of cancer cells to migrate is intimately linked to their ability to induce metastasis. Here the authors show that the sodium channel β4 subunit regulates breast cancer cell migration via inhibition of RhoA activation, independently from its function as an auxiliary protein of the sodium channel.

Functional characterization of genetic alterations is a prerequisite for pancreatic cancer precision medicine. Here, using in vivo CRISPR screens, the authors integrate human cancer genomics and mouse models, identifying that loss of USP15 or SCAF1 accelerates tumor development and leads to reduced inflammatory responses and increased sensitivity to PARP inhibition and Gemcitabine.

A first-order, disorder-driven, superconductor–insulator phase transition is demonstrated. This is in contrast with the usually observed second-order transition and highlights the role of Coulomb interactions between preformed Cooper pairs.

Evidence for the presence of Homo during the Middle Pleistocene is limited in continental Southeast Asia. Here, the authors report a hominin molar from Tam Ngu Hao 2 (Cobra Cave), dated to 164–131 kyr. They use morphological and paleoproteomic analysis to show that it likely belonged to a female Denisovan.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Advances in the design and fabrication of superconducting devices enable physicists to design and monitor quantum electronic systems in synthetic environments. Here the authors observe how many-body effects influence the zero-point motion of a Josephson junction coupled to a high impedance transmission line.

Triggered therapeutics are of interest but currently suffer from limited penetration depth of light sources. Here, the authors report on the development of a system, called radioswitch, that uses ionising irradiation to switch an azobenzene modified drug to an active form for deep tissue triggered therapeutic application.

Forest dynamics are monitored at large scales with remote sensing, but individual tree data are necessary for ground-truthing and mechanistic insights. This study on high temporal resolution dendrometer data across Europe reveals that the 2018 heatwave affected tree physiology and growth in unexpected way.

TMAO is known to be atherothrombotic. Here the authors show that i) kidney function is the main determinant of serum TMAO, ii) TMAO increases kidney scarring with TGF-β1 signalling and iii) anti-diabetic drugs with reno-protective properties such as GLP1R agonists reduce plasma TMAO.

Duquenne et al. show that tanycyte leptin receptor expression is required for leptin to enter the brain and regulate peripheral lipogenesis and pancreatic β-cell function.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

There is still a limited understanding of mechanisms of sensitivity/resistance to cancer immunotherapy. Here the authors perform in vivo CRISPR/Cas9 loss-of-function screens in mouse lung cancer models, revealing Serpinb9 and Adam2 as regulators of immunotherapy response.

The high persistence of deep soil carbon is controlled by bioenergetic constraints of decomposers resulting from the poor energy quality of soil carbon together with the lack of energy supply by roots due to their low density at depth

Integrative genomic and transcriptomic analyses reveal molecular events defining Richter transformation from CLL, and highlight the potential of cell-free DNA for early detection.

The precise timing of neurodevelopmental splicing switches and the underlying regulatory mechanisms remain poorly understood. This study identifies two major waves of developmental switches under the control of distinct combinations of RNA-binding proteins in central and peripheral nervous systems.

The authors perform meta-analysis of GWAS studies for asthma from multiancestral cohorts. They identify five new loci and find that the asthma-associated loci are enriched near enhancer marks in immune cells.

A conserved microRNA targets LTR retrotransposons in Arabidopsis pollen, stimulating epigenetically activated siRNAs in a dose-dependent manner through RNA Pol IV. These miR845b-dependent easiRNAs mediate the interploidy hybridization barrier that leads to seed abortion.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

The field of wavefunction engineering using intraband transition to design infrared devices has been limited to epitaxially grown semiconductors. Here the authors demonstrate that a device with similar energy landscape can be obtained from a mixture of colloidal quantum dots made of HgTe and HgSe.

Artificial intelligence (AI) is transforming prostate cancer management from diagnosis to treatment. AI tools have been designed for the analysis of digitized histopathology and MRI scans, generation of synthetic CT scans and improvement of robotic surgical outcomes. This progress underscores the need for regulation and the development of safe, ethical and non-biased software.

The inhibitor of kB kinase (IKK) is a central regulator of NF-kB signalling. Here the authors identify a motif conserved in substrates of canonical and alternative NF-kB pathways which mediates docking to catalytic IKK dimers: they show that phosphorylation of the conserved tyrosine suppresses the docking interaction.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

RAS-induced senescence is a safeguarding process against tumour development. Here, the authors show that RAS activation destabilises the transcription factor ZNF768, which blocks ZNF768- dependent repression of p53 activity and thus induces senescence.

The development of hybrid wheat cultivars is hampered by the lack of an effective way to control male fertility in breeding lines. Here, the authors report the identification of two restorer-of-fertility genes Rf1 and Rf3 that can restore fertility of wheat plants carrying Triticum timopheevii-type cytoplasmic male sterility.

Microtubule-associated protein 6 (MAP6) is known to be important for synaptic plasticity and cognition, supposedly via interaction with microtubules. Here, the authors found that MAP6 is crucial for the stabilisation of enlarged synapses through its association with a different cytoskeletal element, actin.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Chiou et al. provide a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques.

Green and colleagues characterize LC3-associated phagocytosis as a process that depends on Rubicon, Beclin-1, UVRAG and VPS34 but not on canonical autophagy proteins.

Here, the authors report phonon transmission through a nonlocal material slab embedded in a local material and perform an analysis based on a one-dimensional mass-and-spring model. Evidence of rich phonon behaviours, including sharp resonances related to bound-states-in-the-continuum, are found and reproduced by a developed higher-order-gradient effective medium theory for nonlocal materials.