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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.

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.

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.

Understanding the mechanisms of chemoresistance in multiple myeloma (MM) remains elusive. Here, the authors identify a long non-coding RNA termed as PLUM that is overexpressed in NF-ĸB mutant high-risk MM and interacts with EZH2 to mediate PRC2 complex formation promoting chemoresistance via the activation of the UPR pathway.

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.

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.

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.

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.

Noise in high-speed fluorescence imaging limits real-time analysis of neural dynamics. We present FAST, a lightweight deep-learning framework that leverages spatial-temporal redundancy for calcium, voltage, and volumetric imaging, enabling real-time denoising at >1000 fps.

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.

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.

A highly mobile adeno-associated virus with high tropism for pulmonary arterial smooth muscle cells prevents and reverses the development of pulmonary arterial hypertension in mice and rats.

Catalytic ammonia synthesis continues to attract significant interest. Here, the authors develop a model to explain a large body of recent experimental data on new promoters. They find new promotion mechanism mediated by coupling between adsorption and spin polarization on the surface atoms of magnetic catalysts.

Non-Hermitian physics extends criticality beyond conventional Hermitian systems. Here, the authors report a universal many-body critical skin effect arising from the interplay of multiple pumping channels and interactions, revealing new collective edge phenomena and real-to-complex transitions.

Apoptotic cells often release extracellular vesicles that aid in their clearance and provide molecular information to cellular neighbours. Here, the authors show that some adherent apoptotic cells also create vesicles that remain attached at the site of death.

So-called two-dimensional superconductivity has been reported in several material systems but just how thin a system can be and maintain a superconducting state has been difficult to determine. Da Jiang and colleagues demonstrate that Bi2Sr2CaCu2O8+xcontinues to be superconducting even when it is just half a unit cell thick.

An electrostatic-repulsion-enabled advanced transfer technique based on ammonia solution is introduced for separating van der Waals thin-film materials from their substrates, demonstrating suitability for its use in the complementary metal–oxide–semiconductor (CMOS) industry.

Here, authors present a photoactivated gas sensor integrating conductive MOFs with micro-LEDs for room-temperature, low-power detection. Tailored film design and deep learning enable fast, reversible gas recognition, advancing chemiresistive sensing

Due to rising resistance, efficient routes to new antibiotics is a vital task for human health. Here, the authors report a short, convergent and elegant synthesis of a very recently reported antibiotic, successfully giving access to this material on scale.

Lithium-rich layered oxides, promising high-energy-density cathode materials, face electrochemical degradation due to structural disordering. Here, the authors report that slab gliding is a key trigger of this disordering and a pivotal unexplored avenue for a reversible anionic redox reaction.

CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Here the authors use gene linkage to show that in males inheritance bias of wGDe did not occur by homing, rather through increased propagation of the donor drive element.

Across qubit platforms, improving coherence often compromises operational speed. Here, the authors overcome this trade-off by electrically controlling a hole spin qubit in a Ge/Si core/shell nanowire, achieving triple manipulation speeds while quadrupling coherence times.

Moisture sorption is a common occurrence in polyelectrolyte systems, but not yet fully understood. Here the authors, combining thermogravimetric analysis, vibrational spectroscopy, molecular force field and quantum chemical computations, provide insights into the binding of water in monovalent conjugated polyelectrolytes, establishing a model of the surface hydration of the ion clusters.

Polymer gels have potential in both flexible electronics and impact protections materials, but the balance between stiffness and toughness can be hard to achieve. Here, the authors report a gel with high-density crystalline domains linked by soft chelation crosslinking domains.

CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. Here the authors use transgenic lines with germline-specific regulatory elements to express Cas9 and achieve up to 94% inheritance bias, closing the gap between A. aegyptidrives and the highly efficient drives observed in Anopheles species.

Structural variations (SV) contribute to inter-individual variability. Here, the authors describe a first-generation multi-ancestry Asian SV catalogue containing 73,035 SVs from 8392 Singaporeans to provide insights into Asian SV diversity.

Topological phases with knotted configurations in momentum space have been challenging to realize. Here, Lee et al. provide a systematic design and measurement of a three-dimensional knotted nodal structure, and resolve its momentum space drumhead states via a topolectrical RLC-type circuit.

An algorithm based on concepts established in computational linguistics enables rapid principled design of mRNA vaccines optimizing both structural stability and codon usage, resulting in improved half-life, protein expression and immune responses.

Membrane fouling during electrodialysis, nanofiltration and ultrafiltration processes results in a reduction in the dye/salt fractionation efficacy. Here, authors devise an electro-driven filtration process using tight ion-conductive ultrafiltration membrane for one-step, stable dye/salt fractionation.

SLC19A1 is crucial for transporting folates, antifolates and cyclic dinucleotides. Here authors determined outward-open structures of hSLC19A1 with and without bound substrates, revealing detailed mechanisms of substrate recognition and conformational changes during transport.

The acquisition speed of two-photon fiberscopes is currently suboptimal. Here the authors report advances, including a high-speed scanner and down-sampling scheme as well as a two-stage deep learning (DL) algorithm, to allow high-speed, high-resolution imaging in freely moving mice.

The skin has a remarkable ability to grow under stretch, though the underlying mechanisms remain unclear. Here, the authors show that the mechanosensor Piezo1 coordinates metabolic and immune responses to drive tension-induced skin growth.

Advances in spatial transcriptomics technologies have enabled the gene expression profiling of tissues while retaining spatial context. Here the authors present GraphST, a graph self-supervised contrastive learning method that learns informative and discriminative spot representations from spatial transcriptomics data.

Here, the authors report the heterogeneous integration of 2D HfSe₂ memristor crossbar arrays, Si selectors and peripheral control-sensing circuits, showing improved power consumption and response times. The reported hardware was applied for the implementation of computing-in-memory convolutional neural networks.

Here, the authors develop a genome evolution model to investigate the origin of functional redundancy in the human microbiome by analyzing its genomic content network and illustrate potential ecological and evolutionary processes that may contribute to its resilience.

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.

Wang et al. propose an in-situ dual-lighting System (ISDLS), an approach that enables the simultaneous signal amplification and detection of HER2 nucleic acid and protein in a single pathological section. ISDLS ensures excellent consistency with clinical outcomes for IHC ≥ 1+ and FISH+ sections, as well as improved accuracy for IHC ≥ 1+ and FISH- sections.

Multiple treatment-emergent alterations appear in patients with advanced-stage cancer who were treated with a KRAS inhibitor.

Electric contacts of semimetallic bismuth on monolayer semiconductors are shown to suppress metal-induced gap states and thus have very low contact resistance and a zero Schottky barrier height.

Single-atom catalysts maximize metal atom efficiency and exhibit properties that can be considerably different to their nanoparticle equivalent. Now a general host–guest strategy to make various single-atom catalysts on nitrogen-doped carbon has been developed; the iridium variant electrocatalyses the formic acid oxidation reaction with high mass activity and displays high tolerance to CO poisoning.

In the final report of a phase 1/2 trial evaluating allogeneic CD19-specific CAR-NK cells armored with IL-15 in patients with CD19⁺ hematologic malignancies, the therapy was shown to be safe and efficacious with distinct cord blood features associated with response.

Direct reprogramming of closely-related lineages can generate hematopoietic stem cells. Here, the authors show hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can reprogram fibroblasts into induced hematopoietic progenitors (iHPs), which are engraftable blood progenitors.

Reconfigurable transistors are important for creating compact and efficient neuromorphic computing networks. Here, authors present an antiferroelectric transistor utilizing synergic polarization switching and charge trapping dynamics to perform multiple neuromorphic functions.

Conventional magnetic biosensing technologies have limited ability to detect magnetic field dimensionality. Here, the authors develop a platform which uses DNA hydrogels to spatially engineer a 3D magnetic response and demonstrate its use in the direct and programmable detection of RNA and protein biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease characterized by an immunosuppressive microenvironment. Here the authors show that a subset of P2RX1-negative neutrophils with immunosuppressive properties accumulate in PDAC metastatic liver tissues and promote tumor growth.

Heterophase grain boundaries in memristors based on pentagonal palladium diselenide can guide the formation of conductive filaments during resistive switching, leading to devices with uniform switching properties, low set voltages, long retention times and programmable multilevel resistance states.