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The realization of free-electron radiation in the terahertz band with both compact device size and tunability is challenging. Here, the authors report an on-chip free-electron Cherenkov radiation source tunable from 3.2 to 14 THz at the microscale.

Mesothelin (MSLN)-targeted therapeutic strategy has potential in cancer therapy. Here this group identifies a MSLN-targeting DARPin M7 with specific binding affinity to the protease-sensitive C-terminal region of MSLN, the developed DARPin-drug conjugates demonstrate enhanced tumor control and improved survival benefits in preclinical pancreatic cancer models.

Myxobacteria, particularly Sorangium strains, are rich sources of bioactive natural products but are challenging to genetically engineer. Here, the authors present an efficient electroporation method for multiple Sorangium strains and reveal a revised model of ambruticin biosynthesis.

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.

The discovery of chemosynthesis-based benthic communities at depths of 5,800 m to 9,533 m in the Kuril–Kamchatka and western Aleutian trenches challenges traditional perspectives on the energy sources sustaining hadal fauna.

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.

Tumor pericytes are located surrounding blood vessels, and can regulate tumor vascular structure. Here, the authors discover that a subpopulation of NKX2-3 high tumor pericytes modulates vasodilation and hemodynamics to promote metastasis.

An agent-based large language model (LLM) tool helps with CRISPR-based gene-editing experimental design and analysis.

The efficacy of anticancer gene therapy varies by the delivery efficiency of the mRNA cargo as well as their injection method. Here this group reports using LNP-delivered mRNA encoding 3 C protease treated on three different types of solid tumor models showing effective tumor growth inhibition, with three different injection methods, respectively.

InstructBioMol, a multimodal large language model that achieves any-to-any alignment between human instructions and biomolecules, can effectively leverage natural language to connect complex biomolecular tasks with human intentions.

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.

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.

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

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.

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.

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.

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.

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.

Lignin valorization is hampered by the requirement for expensive cofactors and low conversions. Now a chemoenzymatic platform with coordinated cofactor self-circulation for realizing efficient lignin-to-molecule conversion is reported, facilitating the advancement of sustainable biorefineries.

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.

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.

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.

The sequencing and assembly of the highly polymorphic oyster genome through a combination of short reads and fosmid pooling, complemented with extensive transcriptome analysis of development and stress response and proteome analysis of the shell, provides new insight into oyster biology and adaptation to a highly changeable environment.

The retinal foveola in the primate eye is critical for seeing fine details, color, text and faces. Using ultrahigh-field functional magnetic resonance imaging, Qian et al discover that there is a highly specialized cortical brain region for processing foveolar information.

Adipose tissue macrophage (ATM) has been implicated in inflammation and obesity, but the underlying mechanisms are still unclear. Here the authors show that AMPK is suppressed in ATMs from mice fed with high fat diet, leading to subsequent activation of SUCLA2, over-production of succinate and IL-1β, and ultimately inflammation and obesity.

Liu, Xie and colleagues profile putative cis-regulatory elements in mouse oocytes and pre-implantation embryos. They further validate putative enhancers in oocytes and identify the transcription factors TCF3 and TCF12 as key regulators of folliculogenesis.

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.

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.

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.

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.

Bullous pemphigoid (BP) is a type 2 immunity associated skin inflammatory disease. Here the authors characterize the underlying immune-stromal crosstalk in this disease using scRNA sequencing to show that IL13-IL13RA1 signals are involved with fibroblast and DC mediated enhancement of Th2 responses.

Aryl hydrocarbon receptor (AHR) is an emerging immune-related drug target. Here, the authors report the crystal structures of AHR with six agonists bound, revealing the molecular mechanisms of diverse ligand binding and allosteric activation of AHR.

Layered oxide cathode materials for sodium-ion batteries often experience irreversible phase transitions and structural instability. Now researchers have developed a P2-type oxide containing earth-abundant elements, featuring an intergrowth phase structure that enables long-cycle, high-energy sodium-ion batteries.

Embryo implantation failure is a leading cause of miscarriage, though the mechanisms underlying trophoblast defects are not well understood. Here they show that the histone acetyltransferase KAT8 is essential for proper activation of the trophoblast stemness gene CDX2, and that placental development can be partially rescued by inhibiting histone deacetylase activity.

The cortex is very active during sleep. Wang et al. used macroscopic Ca²⁺ imaging to record the global cortical activity from the entire dorsal cortex of mice during sleep and uncover an unexpected role of the cortex in controlling REM sleep.

Microplastics interacting with cyanobacteria can alter microbial communities and functional genes, impacting carbon and nitrogen cycles in seagrass meadows and posing ecological risks, according to an in-situ incubation experiment in seagrass meadow at Swan Lake, China.

Advancements in proton-exchange membrane water electrolyzers rely on developing oxygen evolution reaction catalysts with high activity and stability. Here, the authors report a method to enhance the spatiotemporal coordination of oxygen radicals in a Ru-based catalyst for improved performance.

Flow batteries provide promising solutions for stationary energy storage but most of the systems are based on expensive metal ions or synthetic organics. Here, the authors show a chlorine flow battery capitalizing the electrolysis of saltwater where the redox reaction is stabilized by the saltwater-immiscible organic flow.

Researchers identify an E3 ligase SGD1 and its E2 partner responsible for grain yield control using foxtail millet, and reveal its conserved role in wheat, maize, and rice. Furthermore, SGD1 ubiquitinates the brassinosteroid receptor BRI1 thus stabilizing it and promoting grain yield in crops.

Soybean accessions display a variable number of nodules when colonized by rhizobia. The authors identify one locus controlling this trait, a typical TIR–NBS–LRR disease resistance gene called NNL1, and the corresponding bacterial effector called NopP.

Estimating the amount of plastics that enters the ocean is subject to significant uncertainty. This study uses ocean plastic abundance data to refine our estimate and reduce this uncertainty, enabling more effective control and mitigation polices.