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Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Li, Lu et al. demonstrate that O-GlcNAcylation enhances angiogenic transdifferentiation from fibroblasts to endothelial cells through a HIRA-dependent H3.3 deposition mechanism and facilitates vascular regeneration.

While it is known in principle that quantum mechanics can enhance operation of microscopic thermal engines, convincing experimental examples of quantum energetic advantages are scarce. Here, the authors successfully showcase a quantum advantage in energy efficiency in a single trapped-ion based device, by demonstrating the benefit from quantum coherence and exploiting suppression of quantum friction effects via counterdiabatic driving.

A computational model called Centaur, developed by fine-tuning a language model on a huge dataset called Psych-101, can predict and simulate human nature in experiments expressible in natural language, even in previously unseen situations.

Kitaev interactions on a honeycomb lattice can potentially lead to a quantum spin liquid state. Unfortunately, materials hosting Kitaev interactions also host Heisenberg interactions favouring long range order. Here, Sakrikar, Shen, Poldi and coauthors find that the relative strength of the Heisenberg and Kitaev interactions can be tuned by pressure in Ag₃LiRh₂O₆.

Rhine et al. find that neuronal aging leads to widespread dysregulation of RNA biology, including mislocalization of splicing proteins like TDP-43, chronic cellular stress and reduced resiliency.

Super spreading events are considered important contributors to the spread of COVID−19, but the extent to which superspreading varies by transmission setting is unclear. Here, the authors demonstrate heterogeneity in superspreading and the generation interval between COVID−19 cases in different settings using data from Hong Kong.

Standard approaches for identifying pleiotropic genetic variants may lead to spurious results. Here the authors present a new statistical method and show that it uncovers five genes linked to metabolites in METSIM participants, which were previously undetected by existing methods.

Miao et al. show that loss of neuronal Vps13d in mice leads to mitochondrial dysfunction, GSDME-mediated mitochondrial DNA release, cGAS–STING inflammatory signaling and activation of microglia, culminating in neuronal loss.

Single-cell and spatial transcriptomics analysis of stricturing Crohn’s disease highlights cellular heterogeneity in fibrotic tissue and identifies neighborhoods of fibroblasts and immune cells contributing to this severe disease complication.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Analysis of shallow-water marine carbonate samples from 101 stratigraphic units allows construction of a record of lithium isotopes from the past 3 billion years, tracking the evolution of the global carbon and silicon cycles.

The bactericidal action of some antibiotics is associated with increased ATP consumption, cellular respiration, and reactive oxygen species formation. Here, Li et al. show that constitutive hydrolysis of ATP and NADH (or ‘bioenergetic stress’) potentiates the evolution of antibiotic resistance and persistence in E. coli.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

In the 12-week, phase 2a DUET study, treatment with TERN-501, a thyroid hormone receptor β agonist, as monotherapy or in combination with TERN-101, a farnesoid X receptor agonist, resulted in dose-dependent reductions in liver fat content as compared to placebo in patients with presumed metabolic dysfunction-associated steatohepatitis.

Kinases regulate cellular processes, making their study essential for understanding cellular function and disease. Here, the authors evaluate methods to infer kinase activity from phosphoproteomics data and provide a toolkit to evaluate future methods.

A conductive, low-melting-point and healable sulfur iodide material aids the practical realization of solid-state Li–S batteries, which have high theoretical energy densities and show potential in next-generation battery chemistry.

Utilizing single-cell RNA sequencing, the authors here find that IL1B gene expression in peripheral blood monocytes associates with smaller HIV-1 reservoir size in people treated during acute infection, suggesting IL1B may be a natural latency reversing factor decreasing the reservoir via NF-κB activation.

Li-dendrite growth is an inherent problem for the application of Li-metal anodes in batteries. Here the authors coat the separator with functionalized nanocarbon with immobilized Li ions, regulating the dendrite growth direction and thereby improving the battery performance.

Lithium-ion batteries are prone to unpredictable failure during fast charging, known as lithium plating. Now, innovative testing protocols can quickly quantify lithium plating and inform battery design strategies to mitigate it.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Parhizkar et al. show that lemborexant, an orexin receptor antagonist, protects against neurodegeneration in male tau transgenic mice by preventing tau protein build-up and inflammation, highlighting its potential for preventing neurodegeneration.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

A neuron-specific isoform of PGC-1α is regulated independently from other isoforms and is repressed with age. Here, the authors show PGC-1α is central in a growth and metabolism networks directly relevant to brain aging.

High-resolution multi-omic profiling indicates widespread gut dysbiosis in individuals with MASLD, also affecting the virome, and reveals microbial signatures that can classify MASLD and its subtypes.

Photoinduced phase transitions in cyanido-bridged Co-W photomagnets change the spin and charge state of both metal centers. Here the authors show that this process is driven by charge-transfer dynamics followed by spin transition within 130 fs.

PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

Lithium metal is considered an ideal anode for high-energy rechargeable lithium batteries, but understanding its nucleation and growth at the nanoscale remains challenging. Using cryogenic transmission electron microscopy and simulations, a structural and morphological evolution scenario for Li deposits is proposed.

The development of solid-state Li-metal batteries has been limited by Li plating and stripping rates and the formation of dendrites at relevant current densities. Single-phase mixed ion- and electron-conducting garnet with comparable Li-ion and electronic conductivities is now proposed to tackle these issues.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Garnet-type electrolytes are attractive for lithium metal batteries due to their high ionic conductivity. A strategy to decrease interfacial impedance between a lithium metal anode and garnet electrolyte is found promising for all-solid-state batteries.

For high-capacity electrodes with anionic redox, the importance of structural dimensionality has not been elucidated. The possibility of triggering anionic redox activity in a tridimensional-ordered Li-rich positive electrode is now demonstrated.

Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants.

A millimetre-scale bioresorbable optoelectronic system with an onboard power supply and a wireless, optical control mechanism is developed for general applications in electrotherapy and specific uses in temporary cardiac pacing.

Intercalation-type metal oxides are promising anodes for Li-ion batteries but suffer from low energy and power density together with cycling instability. A nanostructured rock-salt Nb₂O₅ formed via amorphous-to-crystalline transformation during cycling with Li⁺ is shown to exhibit enhanced performance.

While the impetus to develop lithium metal solid-state batteries is clear, identifying a practical manufacturing process is challenging. Herewith, authors study the underlying mechanisms controlling in-situ anode formation that could enable viable lithium-free manufacturing.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Neural Decomposition (NEURD) is a software package that decomposes neuronal data from high-resolution electron microscopy volumes into feature-rich graph representations to facilitate analysis for neuroscience research.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

Vanadium pentoxide is considered a promising lithium battery electrode, but suffers from poor rate capability and cyclability. Here, the authors synthesize graphene-modified nanostructured vanadium pentoxide and show significant improvement in rate performance and cycle life.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Transient optical spectroscopy applied to studying twisted MoTe₂ for time-___domain detection of fractional fillings of Chern bands reveals many hidden states that have not been previously observed and which could host exotic topological phases.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

This study showed that vagal sensory neurons in the nodose ganglia selectively encode specific cytokines, enabling real-time body-brain communication of immune signals. This neural encoding of cytokines is disrupted during inflammation associated with a colitis model.