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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.

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.

Here, the authors use intracranial electrical stimulation to reveal an anterior to posterior gradient in the fusiform gyrus from internal mnemonic to external perceptual experiences.

The authors add GaSb to PbSe as an n-type dopant to form stable solid solutions with high power factor and high figure of merit. They find that the Ga and Sb atoms co-occupied the Pb sites, causing local structural distortion.

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

A characteristic feature of non-Hermitian systems is an exceptional point at which eigenvalues and eigenstates coalesce. They also support richer degeneracies—a swallowtail catastrophe—that reveals transitions among three different types of singularity.

Auxin signalling requires the degradation of Aux/IAA transcriptional repressors which is mediated by their interaction with F-box proteins. Jing et al. show that in rice, OsIAA11 interaction with the F-box protein TIR1 is enhanced by cyclophilin-dependent cis/transisomerisation of the repressor.

Tear secretion from lacrimal gland is essential for ocular health, but the regulatory role of sympathetic nervous system is unclear. The authors show that sympathetic activation suppresses lacrimal tear secretion and aggravates dry eye disease via NA–Adra1a–Ucp2 signaling.

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.

Hantaan virus is carried and transmitted by rodents and results in asymptomatic infection, yet transmission to humans’ results in symptomatic disease and development of hemorrhagic fever with renal syndrome. Here the authors explore the disparate effects in myeloid cells from mice and humans.

Auxin-driven transcriptional responses are mediated by ARF transcription factors. Here the authors characterize an F-box protein, AFF1, that regulates the accumulation, condensation, and nucleo-cytoplasmic partitioning of ARF19 and ARF7.

Peach is an economically important fruit crop. Here, the authors carry out a large-scale population genomics analysis of peach, describing its demographic history as well as genes associated with domestication and edibility traits.

Drug exposure during pregnancy lacks sufficient fetal safety information world-widely. Here, the authors report the establishment a multi-center birth cohort to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes.

Functional revascularization is vital to the recovery of blood flow. Here, Sun et al. show that myofiber FNIP1 is a negative regulator of muscle functional angiogenesis and revascularization after ischemia by controlling macrophage recruitment.

Lactobacillus-based probiotics have been reported to be beneficial for colitis through incompletely understood mechanisms. Here the authors identify an uncharacterized secreted enzyme named LPH from multiple probiotic Lactobacillus strains, which protects female mice from chemically induced colitis and colorectal cancer via NOD2 signalling.

Chemical libraries with skeleton diversity are important for drug discovery. Here, the authors establish a synthetic methodology-based compound library (SMBL), and apply it to identify a small-molecule inhibitor to interrupt a challenging target:  the protein–protein interaction (PPI) of GIT1/β-Pix.

Green cryogels are highly desirable for soft devices but often formed as crystalline-crosslinked networks due to lack of control of the freezing process. Here, the authors demonstrate a strategy to obtain multifunctional cryogels by total amorphization of the polymer using anti-freeze salts to lower the freezing point of the precursor solution.

The genetic basis of prolactinomas remains poorly understood. Here, the authors find a recurrent hotspot somatic mutation in the splicing factor 3 subunit B1 (SF3B1^R625H) in prolactinomas, and show that this mutation causes aberrant splicing of ESRRG mRNA leading to up-regulation of prolactin.

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.

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.

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.

Pigs can be genetically modified to inactivate endogenous retroviruses and to display enhanced compatibility with the human immune system using a combination of CRISPR–Cas9 and transposon technologies.

Influenza virus is attenuated for vaccine production using PROTAC degradation technology.

In standard computing architectures, memory and logic circuits are separated, a feature that slows matrix operations vital to deep learning algorithms. Here, the authors present an alternate in-memory architecture and demonstrate a feasible approach for analog matrix multiplication.

Here, the authors demonstrate the application of machine learning to optimize the device fabrication process for wafer-scale 2D semiconductors, and eventually fabricate digital, analog, and optoelectrical circuits.

Here, by performing multi-omics microbiome analyses in a cohort of children with new-onset T1D, the authors characterize altered microbial functional and metabolic traits involved in T1D, which they validate in animal experiments, together providing potential avenues for microbiome-based interventions.

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.

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.

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.

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.

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.

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.

Therapeutic options for non-small cell lung cancer patients with brain metastases are limited. Here the authors design B7-H3 targeting CAR-T cells engineered to express the chemokine receptor CCR2b, and show improved accumulation in the brain and enhanced anti-tumor activity in preclinical models of lung cancer brain metastases.

The SEED study is a phase 3 clinical trial demonstrating a beneficial effect on glycemic control of dorzagliatin, a glucokinase activator, in drug-naive patients with newly diagnosed type 2 diabetes.

The deubiquitinase PICI1 is identified as part of an immunity hub that coordinates pattern- and effector-triggered immunity and is involved in conferring broad-spectrum resistance to blast across different subspecies of rice.

A 2D Dirac cone photonic system with inhomogeneous effective mass gives rise to an in-plane synthetic magnetic field, inducing chiral zeroth Landau levels with one-way propagative characteristics.

Lead halide perovskite solar cells use hole-blocking layers to allow a separate collection of positive and negative charge carriers and to achieve high-operation voltages. Here, the authors demonstrate efficient lead halide perovskite solar cells that avoid using this extra layer.

While solid-state batteries offer higher energy densities than liquid-based batteries, such devices require effective ion conduction pathways. Here, authors prepare porous organic cages as solution-processable catholytes that are enable excellent performances from various cathode active materials.