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Hemodynamic management is essential in critical care, but optimal targets for heart rate and blood pressure remain unclear. Here, the authors show that a time-dependent Cox model can derive personalized, real-time targets associated with reduced mortality.

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.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

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.

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.

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.

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.

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.

Single-cell RNA sequencing is used to generate a dataset covering all major human organs in both adult and fetal stages, enabling comparison with similar datasets for mouse tissues.

Electrochemical reconstruction impacts the surface structure of electrocatalysts and is challenging to control in CO₂ electroreduction. Here, by regulating a carbonate shell around an oxide catalyst, the reconstruction is guided towards an abundant low-coordinated structure, achieving a C₂₊ Faradaic efficiency of 82.8 ± 2.2% at a current density of 2 A cm⁻².

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.

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.

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

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.

Co-expression of PD-L1-specific chimeric switch receptors (CSRs) improves the antitumor effects of chimeric antigen receptor (CAR) T cells. Here, CSRs are shown to promote the differentiation of mesothelin-targeting CAR T cells into central memory-like cells and improve their efficacy.

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.

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.

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.

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.

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.

Spatial imaging methods in lipid research can disrupt tissue integrity and can have limited spatial and spectral resolution. Here, the authors present an SRS-based hyperspectral imaging platform to visualise lipids and lipoproteins in a variety of tissues and animal species.

A strategy that depends on attenuated brassinosteroid signalling is described for the design of semi-dwarf wheat varieties with improved grain yield compared with that of green revolution varieties.

The role of cations in the CO₂ electroreduction is crucial, but elusive. Here, the authors combine electrokinetic on a well-defined single-atom catalyst with grand canonical potential kinetics simulations to provide an in-depth study of the interaction of K ⁺ -ions with adsorbed CO₂⁻.

Conventional material processing methods often suffer by strength-ductility trade-off. Here, the authors show high-pressure and high-temperature treatment can transform an eutectic high entropy alloy to having a hierarchical microstructure with simultaneous enhancements of strength and ductility.

While most broadly neutralizing antibodies (bnAb) against Influenza virus target conserved conformational epitopes of the glycoprotein hemagglutinin (HA), Sun et al. characterize a lineage of bnAbs that neutralize group 1 and 2 strains. Structural characterization shows that antibody 28-12 binds a continuous epitope within H3 (group 2) but requires a conformational epitope for H1 (group 1) binding. Comparison of germline-reverted Ab and intermediate mutants provides evidence for an evolutionary adaptation from group 2 to group 1 strain.

Nerve/glial antigen 2 (NG2) glia can sense synaptic inputs from neurons. Here, the authors show NG2 glia form functional GABAergic synapses by regulating inhibitory synaptic transmission onto adjacent hippocampal interneurons, and activation of NG2 glia induces anxiety-like behaviour in a mouse model of chronic social defeat stress.

Developing new carbon resource transformation protocols leading to the production of liquid fuels with high selectivity under mild conditions remains challenging. Here the authors present a novel and energy-efficient catalytic route to directly transform CO and H₂O to liquid fuels at low temperature in aqueous phase.

Chiral receptors with an endo-functionalized cavity for chiral recognition are of interest in the field of molecular recognition. Here, the authors develop chiral naphthotubes containing a bis-thiourea endo-functionalized cavity to effectively recognize neutral chiral molecules with high enantioselectivity.

The metastatic tumour microenvironment in pancreatic ductal adenocarcinoma (PDAC) remains to be explored. Here, the authors perform single cell RNA sequencing analysis for synchronously resected PDAC primary tumours and matched liver metastases and find differences in cellular composition.

Neutrophil-mediated drug delivery has been investigated as a therapeutic approach for brain tumors. Here the authors report the anti-tumor activity of chlorotoxin-directed CAR neutrophils delivering chemodrug-loaded nanoparticles in preclinical glioblastoma models.

The development of synthetic host-guest systems for stimuli-responsive molecular recognition in water is challenging. Here, the authors report a pair of water-soluble naphthotubes with a pH-responsive cavity for which switchable bifunctional recognition in water is achieved.

This paper placed the identified Mariana type ophiolite within a global tectonic re-organization at ca. 530-520 Ma. Similar ophiolites, together with other geological and chemical proxies, newly constrained the timing of establishment of modern plate tectonics, along with its links to surficial changes that characterize the contemporary Earth.

Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

BES1 and BZR1 transcription factors are activated by the BRI1-BAK1 receptor complex during brassinosteroid signaling. Here the authors show that BES1-family members also act in anthers, downstream of another receptor-like kinase-mediated signaling pathway, EMS1-TPD1-SERK1/2, to promote tapetum development.

Cutaneous squamous cell of the skin is a common neoplasm that frequently arises from precancerous actinic keratoses. Here, the authors carry out genomic analysis on matched sets of human lesions and compare with those in ultraviolet treated mice and identify conserved drivers of tumour development.