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Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

KP.3.1.1 S S31del confers enhanced immune escape and increased infectivity, which is counterbalanced by NSP10 S33C. The opposing effects of these mutations highlight the complex interplay of viral genomic elements in shaping their overall fitness.

In this Review, Zhu et al. outline the various CRISPR-based tools recently built for dynamic DNA and RNA imaging, which have provided insights into various molecular mechanisms. The authors also discuss the important parameters to consider when using these tools, and how to approach the quantitative image analysis.

The development of sustainable water oxidation catalysts is crucial for hydrogen production, yet cobalt-based materials often suffer from instability. Here, the authors report that co-doping LiCoO₂ with nickel, iron, and palladium yields a durable electrode with stability of over 2,000 hours.

Non-Abelian topological charges and edge states in a PT-symmetric transmission line network are experimentally observed, and a non-Abelian quotient relation for the bulk–edge correspondence is found.

DEAD-box helicase 6 (DDX6), the regulator of P-body assembly, is essential for the survival of acute myeloid leukemia (AML) cells. Here the authors report that DDX6 undergoes phase separation to preserve mRNA subsets in P-bodies, promoting branched-chain amino acid metabolism and chemoresistance in AML.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Authors present a bispecific antiviral design targeting the virus and the host that simultaneously offers broad-spectrum protection against multiple existing transmissible human-pathogenic coronaviruses, including the Paxlovid-resistant SARS-CoV-2 mutants.

Ziwen Liu et al. report Cytoland, an approach to train robust models to virtually stain landmark organelles of cells and address the generalization gap of current models. The training pipeline, models and datasets are shared under open-source permissive licences.

Confocal Airy beam integrated with single-photon oblique light-sheet tomography (CAB-OLST) is a high-throughput imaging approach for brain-wide mapping of neurons, as demonstrated in cleared mouse brains.

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

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.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

SARS-CoV-2 Omicron XEC variant, a recombinant of JN.1 progeny, shows increased viral fitness and pathogenicity. Here, the authors show that the nucleocapsid mutation R204P enhances inflammation and suggest a growing role of non-spike mutations in viral evolution.

Defective perovskite surfaces limit solar cell efficiency. Liu et al. introduce a small amount of a polar aprotic solvent into the defect passivation solution, enabling surface reconstruction of the perovskite layer and enhancing its overall quality.

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.

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.

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.

Prime editing efficiency is enhanced using a mutated reverse transcriptase and addition of deoxynucleosides.

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.

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.

The signaling mechanisms regulating adipose thermogenesis have not been fully elucidated. Here, the authors show that a brown fat-enriched adipokine ADISSP promotes adipose thermogenesis and improves metabolic health independently of b-adrenergic receptor.

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.

Equitable and accessible education in life sciences, bioengineering, and synthetic biology is crucial for training the next generation of scientists. Here the authors present the CRISPRkit, a cost-effective educational tool that enables high school students to perform CRISPR experiments affordably and safely without prior experience, using smartphone-based quantification and an automated algorithm for data analysis.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

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.

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.

Nationwide implementation of a series of stringent multisectoral air pollution prevention and air-quality monitoring policies in China was associated with reduced hospital admissions for a wide range of cardiorespiratory, neuropsychiatric and kidney diseases due to substantial reductions in PM_2.5 and black carbon pollution over a period of 5 years.

Hong Kong experienced a severe wave of SARS-CoV-2 in early 2022. Here, the authors use genomic and serosurveillance data and show that this wave was dominated by the Omicron BA.2 sublineage, and that low protective immunity, particularly in older age groups, contributed to its severity.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

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.

Horng and colleagues show that mitochondrial glycerol-3-phosphate dehydrogenase, a component of the glycerol phosphate shuttle, modulates a shift from inflammation to immunosuppression in activated macrophages.

A deep learning algorithm shows promising performance in predicting progression to diabetic retinopathy in patients, up to 5 years in advance, potentially providing support for medical treatment decisions and indications for personalized screening frequency in a real-world cohort.

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.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a retinoid derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP.

Accurate segmentation of ischemic stroke lesions from brain MRI is crucial for timely diagnosis and treatment planning. Here, the authors present DeepISLES, an AI ensemble for stroke MRI analysis that outperforms previous methods and matches expert radiologist performance in identifying stroke lesions.

Rational design of live-attenuated RNA viruses with potential as vaccines is enabled by identification of sequence rules for zinc finger antiviral protein.

Coronaviruses exploit the host caspase-6 to cleave coronavirus nucleocapsid protein into fragments with interferon-antagonizing activity to facilitate virus replication.

The co-administration of insulin and pramlintide stabilized with cucurbit[7]uril-conjugated polyethylene glycol in diabetic pigs improves the mealtime suppression of glucagon over the separate administration of the two hormones.

Induced pluripotent stem cell (iPSC)-derived macrophages (iMACs) are being used to make chimeric antigen receptor (CAR) macrophages for immunotherapy. Here the authors design a second-generation macrophage-specific CAR by integrating CD3ζ and toll/IL-1R (TIR) domains resulting in an M1-polarized CAR-iMAC with increased antitumor functions.

An inhibitor of the SARS-CoV-2 main protease (Mpro), Y180, showed therapeutic efficacy against wild-type SARS-CoV-2 and its variants including Omicron after oral administration and improved survival in a humanized mouse model.

Realization of a gyromagnetic double-zero-index metamaterial results in unconventional optical and topological properties, suitable to be used for the generation of light pulses shaped as a vortex both in time and space.

CRISPR-TO, a system for programmable control of spatial localization of cellular RNAs, is presented and enables functional investigation of endogenous RNA localization in diverse living cells.

A method leveraging an integrase-deficient lentivirus, homology-directed repair and the electroporation of a CRISPR-associated ribonucleoprotein complex allows for the knock-in and stable expression of large payloads in primary human cells.

KLHDC2 is a promising E3 ligase for targeted protein degradation (TPD). In this study, the authors demonstrate that heterobifunctional degraders induce cooperative ternary complexes with KLHDC2 and BRD3. They highlight exit vector, neo-substrate, E3 ligase selectivity, and prodrug choice can effectively leverage C-degron E3s for TPD.