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Predicting chemo- and regioselectivity is crucial for understanding and designing chemical reactions. Here, the authors introduce the projection of orbital coefficient vector (POCV) method to predict π electron properties and reactivity vectors

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.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Earth system modeling is used to project future changes in North American wetlands. Climate change will reduce inland wetland areas and disrupt their seasonal regimes, with substantial summer drying and shrinkage in cold regions.

The viral delivery of a miniaturized form of a master protein that establishes dyads (nanostructures involved in excitation–contraction coupling in cardiomyocytes) improved dyad architecture and normalized cardiac function under pressure overload.

Ciliogenesis is negatively regulated by the CP110-CEP97 complex, although the mechanism controlling mother centriole localization is poorly understood. Here, Huang et al. show that KIF24 recruits MMP9 to the mother centriole, where it regulates ciliogenesis by controlling CP110-CEP97 recruitment.

Over the last few years, several van der Waals materials have been found that retain magnetic ordering down to monolayer thickness. These materials provide a simple platform for studying the magnetism in reduced dimensions. Here, Zhong et al study the thickness dependence of magnetic ordering in Cr2Te3, and find a crossover from Stoner to Heisenberg-type magnetism as thicknesses are reduced.

Springtails are omnipresent soil arthropods, vital for ecosystems. In the first global assessment of springtails, this study shows a 20-fold biomass difference between the tundra and the tropics, with distinct temperature-related patterns for diversity and metabolism that suggest climate change may restructure the functioning of soil biodiversity.

The authors investigate the electronic structure of kagome CsCr₃Sb₅ using high-resolution angle-resolved photoemission spectroscopy and ab-initio calculations. The results identify CsCr₃Sb₅ as a strongly correlated Hund’s metal with incipient flat bands near the Fermi level.

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.

Genome-reduced bacteria often show impaired growth under laboratory conditions. Here the authors use adaptive laboratory evolution to optimise growth performance and show transcriptome and translatome-wide remodeling of the organism.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Short hairpin RNAs, expressed from microRNA scaffold–containing vectors, efficiently silence gene expression in female germ cells as well as somatic cells in the fly. A genome-wide resource is being developed.

We have limited knowledge of how aging affects brain vascular structure and function. Here, the authors show that aging induces selective reduction of vasculature and related cell types in key cognitive brain areas and reduces blood oxygenation.

The Kondo hybridization typically occurs in heavy-fermion systems containing f electrons, although recently it has been reported in d-electron systems. Kim et al. report spectroscopic evidence of the Kondo hybridization in FeTe and discuss it role in the mechanism of the magnetic order.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

Endo-lysosomal escape is a highly inefficient process. Here the authors present a lipid-based nanoscale molecular machine that achieves efficient cytosolic transport of biologics by destabilizing endo-lysosomal compartments through nanomechanical action upon light irradiation.

The existence of large number of isomers poses challenges for lipidomic analysis. The authors integrate hydrophilic interaction liquid chromatography, trapped ion mobility, and isomer-resolved MS/MS into a single system, enabling deep profiling of phospholipidomes at fast speed and wide coverage.

Molecular design of acceptor and donor molecules has enabled major progress in organic photovoltaics. Li et al. show that branched alkyl chains in non-fullerene acceptors allow favourable morphology in the active layer, enabling a certified device efficiency of 17.9%.

LMNA-related dilated cardiomyopathy (DCM) is an inherited cardiomyopathy featured by early-onset lethal arrhythmias, but the underlying mechanisms remain unclear. Here, the authors show that manipulation of impaired SIRT1 activity and excessive oxidative stress may offer new therapeutic strategies for LMNA-related DCM.

Implantation-caused foreign-body response is a commonly encountered issue and can result in failure of implants. Here, the authors demonstrate that a highly water soluble, biocompatible, and easily accessible poly-DL-serine hydrogel can mitigate foreign-body response.

Biodegradable implants are of great interest in orthopaedic applications but have been limited by low mechanical strength. Here, the authors examine systematically in detail the strengthening of biodegradable zinc by alloying with beneficial elements using mechanical, biodegradability and biocompatibility testing.

Photoemission studies in the pseudogap state of a cuprate superconductor show differences depending on whether a particle is added or removed, revealing broken translational symmetry. Moreover, this particle–hole asymmetry coincides with the opening of the pseudogap.

Maps of protein-protein interactions (PPIs) help identify new components of pathways, complexes, and processes. In this work, state-of-the-art methods are used to identify binary Drosophila PPIs, generating broadly useful physical and data resources.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Current single-cell tools are limited by the number of proteins they can analyse. Here the authors report a single-cell cyclic multiplex in situ tagging (CycMIST) method for functional proteome profiling of single cells, allowing multiple rounds of multiplexing of the same single cells on a microchip.

Injury poses heavy burden on public health, but little evidence on the potential role of climate change on injury exists. Here, the authors collect data during 2013-2019 in six provinces of China to estimate the associations between temperature and injury mortality, and to project future mortality burden attributable to temperature change driven by climate change.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

1,2-diaminations of double bonds represent a fundamental transformation in organic synthesis, the progress of which has largely been limited to symmetrical delivery of equivalent amine species. Here, the authors report a protocol using azocarboxamides to differentiate carbons of some double bonds, resulting in unsymmetrical diaminations, proceeding under organocatalytic conditions.

Cell adhesion peptides like RGD are important to biomedical applications but suffer from proteolysis as well as processing and cost issues. Here, the authors report on the development of cationic-hydrophobic amphiphilic β-amino acid polymers which function as cell adhesion motifs but are resistant to proteolysis.

Environmental and biotic factors control ecological communities. Here, the authors study community ribosomal rRNA gene copy number in coastal sediment and ocean bacterial communities, and in microcosm nutrient addition experiments, to propose a conceptual framework of how nutrient supply and ecological interactions shape the community.

Machine learning applied to large compendia of transcriptomic data has enabled the decomposition of bacterial transcriptomes to identify independently modulated sets of genes. Here the authors present iModulon-based engineering for precise identification of genes for cross-species function transfer to streamline synthetic biology for strain development and biomanufacturing.

Will snow become cleaner or dirtier in the future? Using Earth System Model simulations, this study reveals a cleaner snow future and highlights its benefits for future water supply from snowmelt.

3D brain atlases enable spatial data integration across studies. Here, the authors present the Developmental Mouse Brain Common Coordinate Framework, a 3D multimodal atlas from embryonic to adult ages for cell type mapping through brain development.

Whole-genome siRNA screens to identify regulators of human LINE-1 retrotransposition reveal that BRCA1 and Fanconi anemia DNA repair factors inhibit retrotransposition at stalled replication fork targets created and exploited by L1.

The authors report in full the primary endpoint data of a pilot clinical trial (NCT 03282656) that used post-transcriptional gene silencing of BCL11A expression to reverse the fetal to adult hemoglobin switch in sickle cell disease. They develop new single-cell flow cytometry and microfluidic techniques to predict the efficacy of HbF induction and show that red blood cells from these patients exhibit greater resistance to deoxygenation-induced polymerization than red blood cells from hydroxyurea-responsive patients.

The gut and oral microbiomes are altered in individuals with rheumatoid arthritis, and these changes can be used to stratify individuals for diagnostic and prognostic purposes.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

High-zinc content aluminium alloys are valued for their wear resistance and are used in aerospace and automotive applications. Here, 400 MPa yield strength and 13.8% ductility are achieved through microalloying to control precipitate formation.