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Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Retrosynthesis aims to identify synthesis solutions for compounds in drug discovery. Here, the authors frame it as a molecular string editing task and utilize an iterative string editing model to provide high-quality and diverse solutions.

The joint analysis of datasets from NOvA and T2K, the two currently operating long-baseline neutrino oscillation experiments, provides new constraints related to neutrino masses and fundamental symmetries.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Spinal muscular atrophy (SMA) is caused by a defect in the SMN1 gene, leading to muscle weakness and motor neuron loss. Here, the authors show that combining CRISPR-Cas9 genome editing with gene supplementation improves survival and motor function in SMA mice, highlighting a potential new treatment avenue.

The introduction of hydrophilic segments into the main-chain of polymer photocatalysts allows water to efficiently enter the interior through these hydrophilic segments, and results in effective water/polymer interfaces for hydrogen evolution.

The pathological identification of lymph node metastasis in whole-slide images is demanding and tedious. Here, the authors design an artificial-intelligence-assisted assessment workflow to facilitate the routine counting of metastatic LNs.

The application of metal carbynoids in catalytic transfer reactions has been hindered by the limited availability of suitable precursors. Here, the authors report a chiral phosphoric acid-catalyzed asymmetric trifunctionalization, utilizing situ-generated α-Halo Rh-Carbenes as metal carbynoids, synthesizing chiral α-cyclic ketal amino esters.

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.

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.

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.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

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.

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.

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.

Converting a carboxylic acid into a boronic acid, which makes a useful chemical handle from a feedstock chemical, currently relies on decarboxylation and requires metal catalysts and prior functionalization. Here the authors show a simplified procedure via deoxygenation, using diboron and free carboxylic acids.

Traditional bromine chemistry uses Br₂, which is environmentally unfriendly and wasteful. Here, the authors design a scalable electrochemical route to synthesize Br-substituted molecules using NaBr over Co₃O₄ under mild conditions and with high selectivity.

The asymmetric inverse-electron-demand oxa-Diels–Alder reaction (IODA) between activated α,β-unsaturated carbonyl compounds with highly polarized alkenes has been reported before but acroleins or simple alkenes were so-far rarely employed as substrates. Here, the authors study the catalytic asymmetric intermolecular IODA reaction between acroleins and simple alkenes.

Symmetry reduction from T to S₄ in coordination cages enables selective recognition of higher fullerene isomers, including D₂-C₇₆, C_2v(2)-C₇₈ and C_2v(3)-C₇₈, presenting a promising approach for fullerene identification and enrichment.

Ortho-C–H and meta-C–H functionalization of arenes is well developed; however, para-C–H functionalization is more challenging. Now, a method for the synthesis of para-functionalized anilides from arylhydroxylamines and O- and S-nucleophiles is reported. The process uses fluorosulfuryl imidazolium triflates at low temperature and probably comprises O-fluorosulfonation, followed by N–O bond cleavage and nucleophilic addition.

Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

In 1972, Erich Clar envisioned Clar’s goblet, a polycyclic aromatic hydrocarbon featuring two unpaired electrons that are spin-paired. However, synthesizing it in a solution phase remains challenging. Now a derivative of Clar’s goblet has been prepared in solution, and spin entanglement at the molecular scale has been demonstrated experimentally.

Dying cells display an “eat me” signal through phospholipid scrambling. Here, the authors show that activation of the plasma membrane-bound Xkr4 scramblase requires extracellular calcium as a “molecular glue” for connecting transmembrane regions.

XBB.1.5 of SARS-CoV-2 is a descendant of XBB.1 and has mutations in spike and ORF8, making it more infectious to humans. Here, the authors examined in detail the differences in virological properties of the two variants.

Machine learning can be used to infer proper retrosynthesis routes for newly designed molecules. Here, the authors develop a multitask graph representation learning model for single-step retrosynthesis inference by exploiting chemical synthesis rules among different entity.

A catalytic method involving coupling of two readily accessible components to construct ortho-quinodimethanes (o-QDMs) is lacking. Herein, the authors describe a palladium carbene migratory insertion enabled dearomative C(sp3)-H activation to form active o-QDM species through the cross-coupling of N-tosylhydrazones with aryl halides.

[n]Peri-acenes have attracted interest as promising candidates for nanoelectronics and spintronics but the synthesis of large (n > 4) [n]peri-acenes is extremely challenging due to their intrinsic open-shell radical character and high reactivity. Herein, the authors report the synthesis and isolation of a derivative of peri-hexacene in crystalline form.

Though designing conductive polymers for memory devices is attractive for future low-cost flexible electronics, a proof-of-concept device has yet to be realized. Here, the authors report a redox-gated polymer memristive processing unit with programmable multilevel storage and logic functionalities.

Multicomponent catalytic reactions that generate enantioenriched boronic esters are underdeveloped. Now an N-heterocyclic carbene–nickel catalyst promotes enantioselective alkene 1,2-carboboration to access multifunctional alkylboronates, bearing a tertiary or quaternary β-stereocentre.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Traditional N-alkylation methods, especially for α-tertiary amines, suffer from limitations due to high energy barriers from steric hindrance. In this work, the authors leverage visible light irradiation to enable organoboronic acid addition to sterically hindered ketimines using a three-component coupling of aliphatic amines, ortho-phenolic ketones, and organoboronic acids.

Axially chiral allenes are important building blocks in organic chemistry due to their potential for functionalization, which can be enhanced by the presence of a synthetically flexible organoboron group. Here, the authors report a stereospecific synthesis of axially chiral alpha-boryl-homoallenyl boronic esters from enantioenriched propargyl carbonates, mediated by copper.

Asymmetric Sonogashira C(sp³)–C(sp) couplings provide complementary approaches to established C(sp³)–C(sp²/sp³) couplings for chiral C–C bond formation; however, relatively few reactions have been developed. Now, a versatile, enantioconvergent Sonogashira coupling via a radical intermediate has been developed. The approach uses a copper catalyst featuring a multidentate electron-rich cinchona alkaloid-derived ligand.

Antiferromagnetic phase transition is observed in a three-dimensional fermionic Hubbard system comprising lithium-6 atoms in a uniform optical lattice with approximately 800,000 sites.

STAT1 promotes ferroptosis and inflammation in hepatic ischemia-reperfusion injury by repressing miR-497-5p and activating HDAC7, revealing therapeutic targets for liver protection.