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Newly emerging SARS-CoV-2 variants underscore the need for broad-spectrum antiviral solutions. This study shows a macrocyclic peptide inhibitor that locks the SARS-CoV-2 spike trimer into a “closed” conformation by engaging a conserved region, and demonstrates that intranasal administration of the peptide inhibitor protects against Omicron variants.

CXCR4 is a less-studied co-receptor for HIV entry that also serves as the receptor for the chemokine CXCL12. In this study, the authors reveal how HIV-2 engages CXCR4 and how CXCL12 inhibits this interaction, uncovering structural features that underlie viral specificity and inhibition

Bioelectronic sensors can use bacteria to detect toxins as electrical signals but are limited to single analytes. Here, the authors combine synthetic biology and electrochemistry to create a multi-channel bioelectronic sensor that detects multiple toxins and encodes digital output.

Here, in a study of over 6,000 women across China, the authors show that Mycoplasma hominis infection strongly influences vaginal microbiota and is linked to higher risk of cervical lesions, highlighting its importance in women’s reproductive health.

Growth factor signalling has been shown to alleviate tissue fibrosis and promote repair. Here, the authors use fibroblast growth factor 7 (FGF7) knockout mice and an FGF7-loaded hydrogel to show that this factor can promote functional regeneration of tendon.

Bone repair and osteointegration of implants is more challenging in aging populations, partially due to increasing cellular senescence. Here, Li et al. report a strategy for implant surface modification which targets senescent cells by modulating their metabolism to promote implant osteointegration.

The contribution of the extracellular matrix and its degradation to the aging process is not well understood. Here, the authors show that degraded elastin fragments, which increase in the circulation with age, promote aging, while counteracting elastin fragment signals alleviates inflammation, promotes healthy aging and extends lifespan.

This study identifies BAG3 as a conserved immune regulator in plants and demonstrates that its cleavage by metacaspase 4 triggers cell death and antiviral defense, offering a potential strategy for engineering virus-resistant crops.

In a multicenter, open-label, randomized phase 2 trial, neoadjuvant chemoradiation with PD-1 blockade elicited a pathological complete response rate superior to that with neoadjuvant chemoradiation alone in patients with locally advanced rectal cancer.

Oncolytic viruses have been tested in patients with malignant glioma, however clinical efficacy remains limited. Here the authors report the results of a phase I trial of Ad-TD-nsIL12, an oncolytic adenovirus expressing a mutant (non-secreting) form of IL12, in patients with high-grade glioma.

Treating acute disease like anaphylaxis is challenging due to the inability to administer therapeutics in a timely manner and regulate pharmacokinetics precisely within a short time window. Here the authors develop active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management.

The authors present a ligand-anchoring strategy for fabricating oriented MOF membranes, enabling precise He/CH₄ separation and concentrating He from 0.3% to 99.9%. This approach highlights the design of efficient MOF-based separation materials.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

The gut microbiota bacterium Ruminococcus gnavus is implicated in the development of cirrhotic liver encephalopathy through the production of neurotoxins.

Geopolymers formed in the mineral-catalyzed reaction of organic molecules act as electron shuttles to accelerate microbial dissimilatory iron reduction, which severely threatens the stability of the iron-carbon association in anoxic environments.

The authors report a flexible thermoelectric film, comprising Ag₂Se and reduced graphene oxide, achieving a power factor of 37 μW cm⁻¹ K⁻² in the film and a normalized power density of over 9.8 μW cm⁻² K⁻² in the out-of-plane device.

Conversion electrodes with fast charging capability and extended lifespan remains challenging. Here, authors developed Cu_0.88Sn_0.02Sb_0.02Bi_0.02Mn_0.02S_0.9Se_0.1 with entropy-driven fast-charging capability as negative electrode for sodium-ion batteries, enabling fast charging up to 100 A g⁻¹.

Here, the authors provide structural and mechanistic insights into psilocybin biosynthesis enzymes, encompassing L-tryptophan-specific decarboxylase PsiD, 4-hydroxytryptamine kinase PsiK, and methyltransferase PsiM. The antidepressant properties of psilocybin intermediates in mice are evaluated.

Electronic wound bandages have to balance conformability and wound healing properties. Here, the authors develop a smart patch (iSAFE) using biomaterials with bioelectronics to facilitate permeability with waterproofing. This achieves intelligent wound management with real-time wound monitoring and active therapy.

A detailed understanding of particle stopping in matter is essential for nuclear fusion and high energy density science. Here, the authors report one order of magnitude enhancement of intense laser-accelerated proton beam stopping in dense ionized matter in comparison with currently used models describing ion stopping in matter.

Activation of the cGAS-STING pathway has been associated with the promotion of anti-tumor immunity. Here the authors show that TET2 upregulates tumor cGAS to activate STING in endothelial cells, inducing tumor vascular normalization and enhancing efficacy of anti-PD-L1 alone or combined with IL-2 in liver cancer preclinical models.

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.

No method exists for real-time evaluation of the status of spinal implants. Here, the authors developed a bio-adhesive metal detector array (BioMDA) that provides a wearable, non-invasive solution for positional analyses of osseous implants within the spine.

This review systematically summarizes the recent advances in organic small-molecule NIR-II fluorophores for phototheranostics, providing insights into further innovation and facilitating clinical translation.

Annotating functional elements of the genome helps the interpretation of genetic variation. Here, the authors compile functional genomics data for the pig genome over 14 tissues with 15 different chromatin states, integrate the data with WGS and GWAS data, and compare conservation of regulatory elements across mouse and human tissues.