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N-Cyano amides are pivotal in agrochemicals, biologically active compounds, and nitrogen-containing heterocycles synthesis. Here, the authors report nucleophilic cyanation reactions using O-tosyl hydroxamates as nitrogen electrophiles for the synthesis of N-cyano amides.

This work demonstrates superadiabatic topological pumping on photonic chips, achieving a 20-fold device miniaturization and high-efficiency operation across a 650–920 nm bandwidth, paving the way for ultracompact integrated photonic transports.

METTL3 promotes healthy placenta function by regulating m⁶A methylation and histone epigenetics. Deficiency in METTL3 leads to premature senescence, inflammation activation of trophoblasts, contributing to pregnancy complications like preeclampsia.

The development of macrocyclic hosts with high-affinity 1:2 recognition capabilities is crucial for its applications. Here, the authors introduce enantiopure chiral macrocycles with remarkable 1:2 recognition properties in water comparable to those of cucurbit[8]uril.

Lu et al. characterize cis-regulatory element dynamics at different stages of colorectal cancer progression and identify a functional variant associated with increased colorectal cancer risk because of selective transcription factor binding.

Single-photon sources with a single-photon efficiency of 0.60, a single-photon purity of 0.975 and an indistinguishability of 0.975 are demonstrated. This is achieved by fabricating elliptical resonators around site-registered quantum dots.

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.

The transcription-independent function of trimethylation of histone H3 (H3K4me) in cell division is unclear. Here, Heng-Yu Fan and colleagues report that CFP1, a subunit of the H3K4 methyltransferase, is required for oocyte meiosis, being phosphorylated and degraded during cell cycle transition.

Three-dimensional (3D) reconstruction from computed tomography could significantly contribute to guiding lung cancer surgery, but requires comprehensive clinical validation. Here, the authors test the effectiveness of an AI-driven 3D reconstruction system for lung cancer surgery in a retrospective, multi-center, multi-reader, multi-case study.

Using two cohorts, Liu, Ge, Xiao, Lu and colleagues perform plasma metabolomics and lipidomics, linking reduced sarcosine to sarcopenia diagnosis. In mice, they demonstrate that sarcosine enhances muscle repair, boosts adipose thermogenesis and preserves muscle mass via macrophage modulation.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

Cryo-electron microscopy structures of the noradrenaline transporter in the apo state, bound to noradrenaline and bound to various antidepressants shed light on the substrate transport, molecular recognition and dimeric architecture of this protein.

Preliminary results from a phase 2a trial involving 71 patients suggest that a new agent, discovered and designed with artificial intelligence assistance, is safe and effective for the treatment of idiopathic pulmonary fibrosis.

A method for acetylome profiling requiring a low quantity of hematopoietic stem cells (HSCs) was developed, revealing a significant reduction in H4K77ac in aged HSCs, associated with decreased lymphocyte differentiation potential.

The germline is established during embryogenesis when primordial germ cells are first specified. Here they show that the RNA-binding proteins DND1 and NANOS3 function together to repress the translation of SOX4, restricting the germ cell lineage specification during embryonic development.

Signet-ring cell carcinoma (SRCC) is a unique type of gastric cancer with no prognostic features. Here, the authors report a CLDN18-ARHGAP26/6 gene fusion in patients with a high signet-ring cell content, poor survival outcomes, and who experience no benefit from platinum/fluoropyrimidines-based chemotherapy.

Cancer-associated fibroblasts (CAFs) are a predominant and critical component of the tumour microenvironment. Here, the authors integrate and analyse single-cell RNA-seq data of CAFs across 10 common solid cancer types, identifying their plasticity and interactions with other cell types.

Low complexity (LC) domains can drive the formation of both amyloid fibrils and protein droplets. Here, the authors identify reversible amyloid cores from the LC of hnRNPA1, based on which they elucidate the structural basis of reversible fibrillation and its interplay with hnRNPA1 droplet formation.

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.

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.

Pseudotyping messenger RNA-packaging virus-like particles with a glycoprotein recognizing a surface protein on dendritic cells led to higher humoral and adaptive immune responses in mice.

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.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

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.

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.

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.

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.

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.

Nanosized zeolites enable better catalytic performance; however, their synthesis is non-trivial. Here, a simple treatment is presented that enables the growth of nanosized fins on zeolites that act as pseudo-nanoparticles, reducing deactivation rates for methanol-to-hydrocarbon catalysis.

The deacetylase SIRT1 regulates IRF3/IRF7-mediated antiviral interferon signaling. Here the authors show that SIRT1 deactylates the DNA-binding domain resulting in liquid–liquid phase separation of IRF3/IRF7 and that this signaling is inhibited in aging, an effect that can be reversed with a SIRT1 agonist to restore antiviral response.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

It is feared that reprogramming may introduce DNA mutations. Here Bhutani et al. take three different reprogramming methods and using comparative whole genome analyses do identify nucleotide variations that are different in reprogrammed cells from the original fibroblasts, but none convey oncogenic potential.