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Non-Annex I countries—mostly developing countries under the UN climate framework—excluding China accounted for approximately 61% of hydrofluorocarbon emission growth during 2011–2020, while China’s emissions have been overestimated since 2017, according to atmospheric observational data and inverse modelling.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Stanage et al. identify a role for transfer RNA nuclease SLFN11 in replication-stress-induced cell death in cisplatin-treated cells lacking PrimPol. SLFN11 is activated upon single-stranded DNA accumulation at stalled forks followed by replication protein A exhaustion and cell death.

Mammalian DNA replication relies on various helicases and nucleases to ensure accurate genetic duplication, but how these enzymes are properly directed is unclear. Here, the authors identify USP50 as a key protein for promoting ongoing replication, restarting stalled forks, maintaining telomeres, and ensuring cell survival.

EXO1 performs multiple roles in DNA replication and DNA damage repair (DDR), but its role in DDR-deficient cancers remains unclear. Here, the authors find EXO1 loss as synthetic lethal with many DDR genes involved in various cancers, including genes from Fanconi Anaemia pathway, BRCA1-A complex, and spliceosome factor ZRSR2; such interactions represent potential clinical targets.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

Prion diseases can be transmitted across species. Here the authors use solid-state NMR to study prion protein (PrP) amyloids from human, mouse and Syrian hamster and show that their structural differences are mainly governed by two residues, which helps to understand interspecies PrP propagation on a molecular level.

The authors present the results of a phase I/II clinical trial using autologous CD133+ bone marrow stem cell therapy to restore fertility in patients with Asherman Syndrome. The intervention was safe and showed promising results for the restoration of menstruation and reproductive function.

Transferrin receptor (TfR) and CD98hc are increasingly used to enable more effective drug delivery to the central nervous system. Here, the authors reveal comprehensive and distinct brain cellular and whole body biodistribution patterns of TfR- and CD98hc-binding molecules.

Prime editing is a CRISPR methodology whose efficiency declines with distance from the target sequence. Here the authors demonstrate prime editing with prolonged editing window, proPE, which extends the editing distance, enabling the use of prime editing for therapeutic interventions.

Acetaldehyde treatment and whole genome sequencing of human cells reveal no increased base substitution mutagenesis but an induction of structural genomic alterations mirrored by the association of similar events with alcohol consumption in cancer.

The emerging field of imaging-by-sequencing aims to perform spatial biological analyses by molecular interactions. Here, authors used previously undiscovered spatial networks within Slide-tags data to reconstruct cell positions and capture biological information comparable to the original method.

RBM10 is the most mutated splicing factor in lung cancer. The authors reveal a non-canonical role of RBM10 in regulating DNA replication stress response. They also identify an arsenal of RBM10 synthetic lethal genes, such as WEE1, that can be therapeutically harnessed with immediate applicability.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

In operando three-dimensional X-ray imaging of a 1T-TaS₂ cryomemory device reveals van der Waals layer restacking, resulting in a bulk metallic switching region, driven by charge rearrangement and concomitant lattice strain.

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.

The enteric nervous system integrates microbial cues to regulate gut function. Using an optogenetic gut culture model, authors show lineage- and frequency-specific neuronal control of immune responses and barrier integrity, shaped by gut microbes.

Our understanding of chromosome organization and dynamics in spherical bacteria, such as Staphylococcus aureus, remains limited. Here, the authors show that chromosome replication and cell division cycles are not synchronized in S. aureus, with cells exhibiting two segregated origins of replication at the start of the cell cycle.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

EU wine geographical indications are bound to a strict regulatory system, limiting their potential to adapt to climate change. In this study, analysis of social, environmental and economic characteristics of over 1000 EU wine regions suggests that innovation and flexibility are key to increase the resilience of European viticulture.

Clear cell renal cell carcinoma (ccRCC) usually metastasizes to the lungs. Here, the authors discover that SWI/SNF ATPase subunit SMARCA4 silencing of HLF regulates ccRCC lung metastasis by modulating the integration of collagen's mechanical cues with the actin cytoskeleton through leupaxin.

Bass et al. and Haahr et al. now identify ETAA1 as a critical replication stress response factor that interacts with DNA damage response proteins and activates ATR to maintain genomic stability.

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.

The SARS-COV-2 pandemic has put pressure on intensive care units, so that predicting severe deterioration early is a priority. Here, the authors develop a multimodal severity score including clinical and imaging features that has significantly improved prognostic performance in two validation datasets compared to previous scores.

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.

A new inhibitor of Mycobacterium tuberculosis leucyl-tRNA synthetase is associated with bactericidal activity in humans and may be a candidate for combination therapy of tuberculosis.

Estimates of the severity of emerging infections did not consider the case ascertainment method, but secondary cases identified by contact tracing of index cases may be more reliable as they are less susceptible to ascertainment bias. Here, the authors perform a systematic review to quantify these differences and model their impacts for COVID-19.

The A.27 SARS-CoV-2 lineage spread globally in 2021 but did not become dominant. Here, the authors show that A.27 shares some mutations in the spike gene that are present in variants of concern, but lacks the D614G mutation, indicating independent evolution of immune escape properties.

Here, Mac Kain and Maarifi et al. perform a functional CRISPR/Cas9 screen to identify SARS-CoV-2 restriction factors in A549 cells. They identify DAXX, a scaffold protein of nuclear bodies with diverse functions, that has anti-viral activity post SARS-CoV-2 entry, while SARS-CoV-2 has evolved a mechanism to counteract its action via PLpro-mediated proteasomal degradation.

Sobkowiak et al., present a comprehensive genomic epidemiology of SARS-CoV-2 in Peru from 2020 to 2024, highlighting the emergence and spread of key variants including Lambda and Gamma P.1.12. The work provides valuable insights into regional viral transmission dynamics in a high-burden, middle-income setting, emphasizing the importance of sustained genomic surveillance.

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.

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.

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.

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.

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.

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.

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.

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.