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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.

An acid-free atmospheric leaching process extracts 97.4% Ni and 98.8% Co from critical minerals, limits iron dissolution (4.7%), and reduces CO₂ emissions by 59.5%, offering a sustainable alternative for battery-grade metal production.

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.

This study presents FolTAC-dual, a folate receptor-mediated platform for dual degradation of EGFR/HER2 and PD-L1/VISTA, offering a strategy to overcome drug resistance and enhance antitumor immunity for cancer treatment.

In contrast to the well-established palladium-catalyzed version, the nickel-catalyzed carbonylative coupling is underdeveloped. Here the authors report a nickel-catalyzed allylic carbonylative coupling with alkyl zinc reagents, allowing for preparation of β,γ-unsaturated ketones in a linear-selective fashion.

A ligand-restricted strategy is developed to realize the synthesis of dual-atom catalysts with high pairing ratio and tunable atomic distances.

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.

Ubiquitination of the GβL subunit, a component of both mTORC1 and mTORC2, acts as a regulatory switching mechanism to balance levels of mTORC1 and mTORC2; the failure of this mechanism in some cancers leads to elevated mTORC2 formation and tumorigenesis.

Fan et al. report a role for PRMT5 in regulating GPX4 stability and ferroptosis sensitivity through arginine methylation, which may be targeted to inhibit tumour development.

Abundance of PD-L1, the ligand of the anti-cancer immunotherapy target PD-1, is negatively regulated by poly-ubiquitination via the cyclin D–CDK4/cullin 3–SPOP axis and PD-1 blockade treatment in mice improved survival when combined with CDK4/6 inhibitors.

Upstream pathways regulating Brg1 stability and their role in carcinogenesis are unknown. Here they show Brg1 to be phosphorylated by CK1δ to promote its ubiquitination by SCF^FBW7 (FBW7), Brg1 stabilization to promote gastric cancer metastasis, and suggest targeting Brg1 in FBW7 compromised gastric cancer.

Triangle-beam interference structured illumination microscopy leverages radially polarized beams to generate two-dimensional lattice illumination patterns. The technique enables a temporal resolution of 242 Hz, spatial resolution of 100 nm and continuous imaging of neuronal growth for up to 13 h.

Wang and colleagues show that an AI-assisted designed peptide obstructs GSDMD pores and inhibits IL-1β and IL-18 release and pyroptosis.

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.

SAP05, a secreted effector of the obligate parasitic bacteria phytoplasma, bridges host SPL and GATA transcription factors (TFs) to the 26 S proteasome subunit RPN10 for ubiquitination-independent degradation. Here, the authors report the details on how SAP05 interacts with SPL5, GATA18 and RPN10.

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

The mechanisms underlying the invasiveness and aggressiveness of pituitary neuroendocrine tumours (PitNETs) remain poorly understood. Here, the authors perform single-cell RNA sequencing and spatial transcriptomics to characterise the tumour microenvironment of PitNETs and identify potential therapeutic targets.

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.

N-degron pathways play an important role in maintaining protein homeostasis. Here, Li et al. demonstrates an additional non-Ac/N-degron pathway, in which N-terminal non-acetylated small residue degrons (Ser, Ala, or Cys) are recognized by CRL2^ZER1/ZYG11B and targeted for protein degradation.

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.

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.

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.

Incompletely synthesized nascent polypeptides resulting from ribosome stalling during translation are under surveillance by ribosome-associated quality control. Here, the authors report the molecular mechanism by which the E3 ligase Pirh2 targets the polyalanine tail of aberrant nascent chains for degradation via the C-degron pathway.

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.

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

Ubiquitination and deubiquitination processes regulate the stability of PD-1, affecting T cell biology. Here the authors identify the ubiquitin-specific protease 5 (USP5) as a deubiquitinase for PD-1 and show that USP5 inhibition in combination with a MEK inhibitor or anti-CTLA-4 could promote anti-tumor immune responses in preclinical models.

The impact of genetic fusions on degrons, which are motifs for ubiquitin-mediated protein degradation, has not been fully explored. Here, the authors analyse fusion genes affecting degrons in pan-cancer genomics data, validate their functional impact and find enrichment for both internal and C-terminal degron losses.

Fluorescent biosensors are important tools for studying cellular metabolism, but development and optimization are challenging. Koveal et al. present a high-throughput multiparameter screen for sensor performance, and used it to generate LiLac, a high-performance, quantitative lactate sensor.

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.

Guo et al. identify SETDB1 and KDM4B as the methyltransferase and demethylase, respectively, for AKT. AKT methylation promotes its kinase activity and the subsequent tumorigenesis.

Zhang, Peng, and colleagues benchmark metabolic RNA labelling chemistries for time-resolved single-cell RNA sequencing, improving in vivo detection of newly synthesized RNA during zebrafish embryogenesis.

mTORC1 regulates beta cell survival, function and adaptation to physiologic and pathological stimuli. Here Niet al. demonstrate that that deficiency of Raptor, a component of mTORC1 complex, impairs insulin secretion and glucose tolerance in mice by affecting maturation of beta cells during the postnatal period.

Programmable optical actuation in a material provides special possibilities for applications. Here, the authors combine photonic crystals with elastomers to provide material composites with tunable deformation and actuation as a function of moving light.

SIRT1 is a stress sensor whose deacetylase activity is increased during cellular stress, but the molecular mechanism is unclear. Here, the authors show that O-GlcNAcylation of SIRT1 is elevated upon different stress stimuli and increases SIRT1 deacetylase activity, protecting cells from stress-induced apoptosis.

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.

Acetylation of histone H3K23 has emerged as an essential posttranslational modification, yet this epigenetic mark remains poorly understood. Here, the authors identify the native MORF complex as a histone H3K23-specific acetyltransferase and show that interaction of the MORF subunit with acylated H3K14 promotes acetylation of H3K23 by this complex to activate transcription.

Structural and biochemical analyses identify the ZZ domain of p300 as a novel histone H3–binding module that promotes p300 chromatin association and is required for selective acetylation of H3K18 and H3K27 in human cells.

Zhang, Xu, Liu, Wang et al. identify an inhibitory mechanism for RIPK1 kinase through EGLN1/pVHL-mediated proline hydroxylation, which is disrupted upon prolonged hypoxia that activates RIPK1 activity to promote cell death and inflammation.

Gastrointestinal stromal tumours (GISTs) are clinically heterogeneous, with varying degrees of aggressiveness. Here, the authors describe the genomic and transcriptomic landscape of 117 GISTs from 105 patients; they find four molecular subtypes as well as recurrent inactivating YLPM1 mutations in high-risk/metastatic GIST.

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.