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Valorizing plastic waste remains a major challenge due to its severe environmental impact. Here, the authors report a CuCo/CoOₓ catalyst constructed via stepwise hydrogen spillover, enabling near-quantitative conversion of waste polyethylene terephthalate to p-xylene.

Unveiling the regulation of mitotic protein degradation is crucial for cancer therapy. Here, the authors reveal that a reciprocal inhibition of PIN1-APC/C^CDH1 controls the cell cycle and mitotic protein degradation, offering a synergistic anti-tumor strategy.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

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.

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.

Here, by constructing a heterostructure with sonic crystals, a topological waveguide is realized by the authors. The waveguide states feature gapless dispersion, momentum-valley locking, immunity against defects, and a high capacity for energy transport.

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.

Enhancing the arsenal of E3 ligases is important for PROTACs development. Here, the authors identify a non-inhibitory aptameric ligand to CRL2^ZYG11B E3 ligase, and develop a general, modular, and straightforward aptamer-based PROTAC platform, termed ZATAC, providing insights for untapped E3 ligases.

The Dark sectioning algorithm removes the background and provides single-frame optical sectioning in fluorescence microscopy. It offers improved quantitative analysis and deep-tissue segmentation accuracy and is compatible to diverse modalities.

Delivering functional proteins or protein complexes into cells continues to be a significant challenge. Here, the authors develop efficient systems by using engineered extracellular vesicles to deliver functional cargoes, including CRISPR/Cas9-ribonucleoproteins, both in vitro and in vivo.

ASB7 acts as the substrate receptor for cullin 5 RING E3 ubiquitin ligase (CRL5), targeting the internal α-helix degron for degradation. Here, the authors elucidate the molecular mechanism of substrate recognition by ASB7 using structural, biochemical and cellular analyses.

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

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.

Here the authors show that the E3 ligase GID4 can be harnessed for targeted protein degradation and present the crystal structure of the GID4–PROTAC–BRD4 ternary complex to elucidate the underlying molecular mechanisms.

Alpha-fetoprotein producing gastric carcinomas (AFPGC) are rare and aggressive. Here, the authors profile AFPGC tumours using whole exome sequencing, and find amplifications in CCNE1 and ERBB2 that are associated with poor outcomes but are potential therapeutic targets, as shown in patient-derived xenografts.

Currently available mitochondria-targeted fluorescent dyes emit only one color in the visible or NIR-I and their applications are limited. Here, the authors develop upconversion mitochondria-targeted NIR-II fluorophores for synchronous upconversion-mitochondria-targeted cell imaging, in vivo NIR-II osteosarcoma imaging and photothermal efficiency

Crystal structures of FEM1C in apo and in complex with a C-degron ending with arginine reveal a binding pocket in FEM1C that recognizes C-degrons and the essential role of C-terminal arginine for recognition.

Abnormal angiogenesis causes many ocular diseases. Here the authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.

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.

The Set8-Set7 methyltransferase plays a critical role in cell cycle progression and tumorigenesis, and is degraded through modification by the E3 ubiquitin ligase CRL4^Cdt2. Here Wang et al. identify SCF^β-TRCPas an additional E3 ubiquitin ligase that marks Set8 for degradation in response to DNA damage.

Precise coupling of different or even contradictory material properties and biological characteristics is needed for tissue engineering but challenging. Here the authors report an all-in-one guided bone regeneration membrane that asymmetrically combines stiffness and flexibility, ingrowth barrier and ingrowth guiding, alongside anti-bacteria and cell-activation.

Regenerative heart valve prostheses rely on interactive materials that can adapt to the remodeling process, but these materials are often based on complex designs. Using 1,1’-thiocarbonyldiimidazole chemistry, the authors propose a double network hydrogel formulation for heart valve regeneration.

Sox2 regulates pluripotency in neural progenitor cells (NPC) but how protein stability affects this is unclear. Here, the authors identify changes in ubiquitylation of Sox2 (by CUL4A-DET1-COP1 ligase and OTUD7B deubiquitylase) as controlling protein stability and so the differentiation state of NPCs.

Porphyrins are produced at scale through metabolic engineering and optimization of CPIII purification.

Shengyue Wang and colleagues report the draft genome sequence and transcriptome analysis for Echinococcus granulosus, a parasitic helminth and cause of human hydatid disease. Their comparative genomic analysis identifies genes acquired by E. granulosus that are associated with host immune response, parasite survival and growth.

Acquisition of CDK4/6i resistance represents a major clinical challenge. Here, the authors report that inhibition of CK1ε can prevent acquisition of CDK4/6i resistance, potentiating the therapeutic efficacy of CDK4/6i in human breast cancer.

The potassium channel KCNQ2 can be activated by analgesics and antiepileptic drugs via an unclear mechanism. Here authors report structures of KCNQ2-CaM in complex with cannabidiol, PIP2, and HN37 and elucidate the mechanisms of activation.

The regulatory mechanisms of PD-L1 posttranslational modifications are not completely understood. Here the authors show that USP8 negatively regulates PD-L1 protein abundance by removing the K63-linked ubiquitination of PD-L1; while USP8 inhibition increases MHC-I expression and triggers anti-tumour immune responses through activating NF-κB signalling.

Spatially resolved proteomics is an emerging approach for mapping proteome heterogeneity. Here, the authors report a method based on the combination of hydrogel-based tissue transformation with mass spectrometry-based proteomics, that enables proteome profiling with a lateral resolution of 160 µm.

Xie and colleagues find that activated mTORC1 growth signalling impairs DNA repair through S6K-mediated phosphorylation and inhibition of the RNF168 ligase.