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Self-amplifying RNA enables durable therapeutic expression, but its high immunogenicity and low-fidelity replication limit its use. Here, authors engineer a Norovirus-derived VPg-saRNA platform that achieves cap-independent, low-immunogenic and precise therapeutic protein expression in vivo.

Phagocytes must safely remove mitochondria released after tissue injury to prevent harmful immune activation. Here, the authors show that TMEM110 preserves lysosomal function to clear mitochondrial DNA, thereby limiting organ damage and mortality after traumatic brain injury.

Intrinsically stretchable electronic devices are interesting for wearable electronics, soft robotics, and stretchable display applications. Here, the authors report the fabrication of intrinsically stretchable solution-processed thin-film transistors based on 2D MoS₂ flakes, showing high performance and stability under strain up to 20%.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Diabetes, a frequent co-morbidity to osteoarthritis, accelerates progression of joint inflammation. Here author show that hyperglycaemia enhances glycolysis in synovial macrophages, leading to increased lactylation of CD11b, which impairs the capacity of macrophages to phagocytose apoptotic cells, which eventually aggravates inflammation.

Here, the authors demonstrate that VGLL4 maintains cartilage integrity by forming a complex with TEAD4-SMAD3 to regulate extracellular matrix homeostasis. VGLL4 deficiency accelerates osteoarthritis, while its restoration or SMAD3 delivery rescues cartilage damage, suggesting therapeutic potential.

2D semiconductors hold promise for the fabrication of high-density flexible integrated circuits, but they often require high-temperature processing or transfer steps. Here, the authors report the low-temperature ( ≤ 150 °C) fabrication of wafer-scale 3Dintegrated flexible complementary circuits based on 2D semiconductor inks.

By resonant excitation of an InAs quantum dot embedded in a microcavity, a deterministic single-photon source is demonstrated. Single-photon purity of 0.9795(6), photon indistinguishability of 0.9856(13), and an overall end-to-end efficiency of 0.712(18) are simultaneously obtained.

It is important to understand the cross-neutralization among distinct SARS-CoV-2 Omicron sublineages. Zou et al. show that sera from Omicron BA.1-infected people are significantly weaker in neutralizing Omicron BA.2, BA.3, and USA-WA1/2020 than neutralizing BA.1.

Quantum information cannot be copied, posing challenges for long-distance communication due to signal losses. Here the quantum relay architecture using a single-photon source enhances the signal-to-noise ratio of quantum information transmission.

The SARS-CoV-2 variant of concern Omicron has quickly spread. Here, Zou et al. develop a high-throughput neutralization test for Omicron SARS-CoV-2 and show that patients with previous non-Omicron infections do not develop robust neutralization against Omicron.

It is essential to test the neutralization of approved vaccines against SARSCoV-2 Omicron sublineages. Kurhade et al. find that sera from people with three doses of BNT162b2 neutralize Omicron BA.1, BA.2, and BA.3 to a lesser extent than the original strain USAWA1/2020.

Imaging the immune activation status of tumor-associated neutrophils (TANs) provides insights for improving cancer immunotherapeutic strategy. Here this group reports a ratiometric nanoprobe responding to tumor microenvironment and enabling NIR-IIb quantitative fluorescence imaging of TANs with overexpression of neutrophil elastase.

Han et al. show that SMARCA5 is required for the sustained expression of genes required for malignancy in pancreatic cells with mutant KRAS. Inhibiting SMARCA5 activity prevents malignant transformation while maintaining pancreatic regeneration.

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.

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.

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.

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.

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.

Samples of serum from individuals immunized with the BNT162b2 vaccine show neutralization activity against engineered SARS-CoV-2s bearing the spike mutations from B.1.617 and other variants.

The synthesis of vinylboronates and alkylboronates often suffers from step-tedious and poorly stereoselective procedures. Here, the authors report a bench-stable redox-active reagent for the radical difunctionalization of alkenes and alkynes affording fluorine-containing vinylboronates and alkylboronates.

Conjugated microporous polymers are highly flexible materials that may be used for gas storage and catalysis applications. Here, the authors report metal-functionalized conjugated microporous polymers capable of both capturing CO₂and functioning as a heterogeneous catalyst in its conversion to propylene carbonate.

Chromosome-level genome assemblies of nine tetraploid and two diploid wild Oryza species provide insights into genome evolution within the genus Oryza and the potential for crop improvement and neodomestication.

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.

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.

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.

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.

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.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

Targeted deletion of integrin-associated protein CD47 enhances long-term engraftment of human CD34⁺ cells in immunodeficient pigs lacking IL2RG and RAG2, enabling large-scale production of functional human immune cells.

Using a thermal evaporation approach and lead chloride (PbCl₂) as a reaction initiator, caesium tin iodide (CsSnI₃)-based p-channel thin-film transistors can be fabricated that exhibit average hole field-effect mobilities of around 33.8 cm² V⁻¹ s⁻¹ and improved stability compared with solution-deposited devices.

Biotic-abiotic hybrid systems are promising for solar-to-chemical conversion, but it remains challenging to achieve atomically precise interface contact. Here, the authors report a general strategy of facilitating direct electron uptake via building single-atom bridges across biotic-abiotic interfaces to enhance solar-driven hydrogen production.