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Gravitationally induced stratification during self-assembly often leads to density driven vertical segregation limiting the synthesis of metastable nanofilms. Here, the authors address this limitation with an antigravity confined interfacial self-assembly synthesis where capillary forces dominate and enable precise molecular organization resulting in ordered and stable nanofilms.

Mi et al. use de novo protein design to address bystander and off-target editing in base editing, resulting in a highly precise mitochondrial cytosine base editor that is valuable for studying and treating mitochondrial diseases.

This study introduces ChemAHNet, a deep learning model that predicts stereoselectivity and absolute configurations in the asymmetric hydrogenation of olefins with two prochiral centers, providing a broadly applicable tool for catalyst and substrate design.

Alternative splicing (AS) is a source of transcriptomic heterogeneity, but analysing splicing changes at single-cell level is challenging due to dropout, noise, and limited coverage in scRNA-seq. Here, the authors propose SCSES, a tool to identify AS events and estimate splicing intensity at single-cell resolution. SCSES reveals high splicing heterogeneity beyond conventional expression-based clustering.

An eco-friendly and sustainable NH₃ desorption process has been successfully realized in a bipyridinium-bearing MOF adsorbent via free radical-dominated photothermal conversion for localized heating.

Functional succinate dehydrogenase (SDH) complex is vital to mitochondrial homeostasis. Here the authors show that disruption of SDH assembly in the heart causes dilated cardiomyopathy via impairing the mitochondrial integrity and metabolism and that mitochondrial interventions can be an effective approach to ameliorate the disease progression.

Human guanylate kinase (GMPK) is the sole enzyme for GDP biosynthesis contributing to antiviral prodrug activation and tumorigenesis. Here, authors profile the ligand-specific conformations of human GMPK along with the reversible catalytic pathway.

Non-nucleotide stimulators of interferon gene (STING) agonists hold great promise as the immunotherapeutic agents for cancer therapy. Here, this group reports incorporating STING agonist MSA-2 and DOX in the separate layers of 3D-printed polymeric scaffold for effectively activating STING-IFNβ pathway, enhancing DAMPs release thereby suppressing postsurgical tumor recurrence and metastasis.

The authors propose a set of guidelines for far-UVC optical design, under which the multi-stimulated far-UVC luminescence at 222 nm in Pr³⁺ -doped SrF₂ is realized, offering unique opportunities for solar-blind imaging and structural health monitoring in complex environments.

Simultaneous targeting of BCL-xL and BCL-2 is an attractive approach for cancer treatment. Based on information gained by computational structure modelling, the authors develop a PROTAC that induces degradation of both BCL-xL and BCL-2 and effectively targets BCL-xL/2-dependent leukaemia cells.

Gluconeogenesis produces glucose from non-carbohydrate carbon substrates, particularly occurs during fasting. Here, the authors show lysine methyltransferase KMT5C promotes gluconeogenesis by decreasing PGC-1α degradation, which is independent of its methyltransferase activity.

Current classification systems of pituitary neuroendocrine tumors (PitNETs) rely on histological hormone staining and transcription factors. Here, the authors analyze alternative splicing at bulk and single-cell resolution in PitNETs, revealing additional subtypes associated with worse clinical outcomes and splicing abnormalities.

Although structurally ordered intermetallic nanocrystals are promising electrocatalysts for fuel cells, their high-temperature large-scale preparation has proved challenging. A low-melting-point-metal-induced bond strength weakening strategy to promote alloy catalyst ordering is now proposed.

This study identifies argininesuccinate lyase, a key member of the urea cycle for arginine biosynthesis, as an important molecular component of rice root tolerance to ammonium and so as a potential lead to improve nitrogen use efficiency and yield.

Cancer vaccines based on endogenous modified dendritic cells can activate cytotoxic T cells in an antigen-specific manner, but the short life of dendritic cells on injection in the body limits the efficacy of the strategies. Here the authors design biomimetic nanovesicles derived from antigen-presenting dendritic cell membranes for cancer vaccination and the simultaneous delivery of immune co-stimulatory molecules, showing robust antitumour activity in animal models.

Resistance to ferroptosis in hepatocellular carcinoma remains to be understood. Here, the authors identify S100 calcium binding protein P (S100P) as a ferroptosis suppressor in HCC cells, which promotes lysosomal degradation of acetyl-CoA carboxylase alpha (ACC1) to downregulate lipid biosynthesis.

The first BCL-X_L-degrading PROTAC achieves safer and more potent antitumor activity than dual BCL-X_L and BCL-2 inhibitor navitoclax because of reduced dose-limiting platelet toxicity and high target specificity.

Senolytics have the potential to extend healthspan by selectively killing senescent cells (SCs), but senolytics that target Bcl-xl may cause platelet toxicity. Here, the authors generated a Bcl-xl proteolysis-targeting chimera (PROTAC) senolytic, which effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia.

The genome of the scallop Patinopecten yessoensis is sequenced. This bivalve mollusc has a slow-evolving genome with features such as karyotype and Hox gene expression that may be close to that of the ancestral bilaterian.

Urea is an essential fertilizer; however, its production is carbon and energy intensive. This work shows a pulsed co-electrolysis strategy that turns carbon dioxide and nitrate to urea directly utilising a molecular electrocatalyst.

This study reports that the SOMBRERO, a root cap-localized transcription factor, determines root halotropic response to salt stress via spatiotemporally modulating AUX1-depdenent auxin redistribution in the root tip.

While material defect sites are active for chemical reactions, it is important to understand how different defect types impact reactivity. Here, authors prepare Frenkel-defected MoS₂ monolayers and demonstrate improved performances for H₂ evolution electrocatalysis than pristine or doped MoS₂.

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.

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.

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.

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.

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.

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.

While monolayer of 1T-TaS₂ is considered to be a Mott insulator, the nature of the bulk insulating state is debated. Here the authors introduce a ladder-type structures with fractional misalignment of adjacent layers, showing that it becomes a Mott insulator due to decoupling between the layers.