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The mechanism of HIV-1 latency reversal remains unclear. The authors suggest that PRMT3 drives the reversal by enhancing chromatin accessibility to form a transcriptional hub containing TEAD4 and P-TEFb at the viral promoter.

Using nanopillars with increased spatial resolution, Shiu et al. identify high perinuclear forces that originate from contractile apical actin filaments that span across the nucleus and are dependent on lamin A and the LINC complex.

Post-translational modifications regulate tumorigenesis and cancer therapy sensitivity. Here, the authors show that N-glycosylation defective Interleukin-6 (deNG-IL6) switches downstream signalling pathway from JAK-STAT3 to SRC-YAP axis and lung cancer cells secrete deNG-IL6 to promote metastasis and tyrosine kinase inhibitor resistance.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Vapour-phase methods are promising for nanomaterial synthesis but the vaporization of different precursors for the synthesis of a broad nanomaterial space is challenging. Here electrified vapour deposition generates ultrahigh-temperature, high-flux atomic vapour at atmospheric pressure to rapidly vaporize diverse precursors, enabling the synthesis of multi-elemental nanomaterials with uniform compositions and tunable structures.

Digital proximity ligation assay (dPLA) can measure proteins and mRNAs in single cells, but is not compatible with cell imaging and cannot quantify rare proteins due to a high dilution factor. Here the authors present an automated microfluidic device that combines live-cell imaging, chemical stimulation, and dPLA in a smaller reaction volume.

How metabolic signals are sensed by the cell cycle machinery remains unclear. Here, the authors demonstrate that the glycolytic enzyme PFKM acts as a citrate sensor to promote mitosis, coupling metabolic activity to cell cycle regulation.

The phase 3 STEER trial showed that a single intrathecal dose of onasemnogene abeparvovec significantly improved motor function in children and adolescents with spinal muscular atrophy versus sham, with a similar and acceptable safety profile.

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.

This study used accelerometer data from participants of the UK Biobank to reveal associations between sedentary and physical activity levels and mortality in people with epilepsy. These associations differ between people with epilepsy and the general population.

The commercialization of organic solar cells has been hindered by the limited device stability. Here, authors show that the connectivity of electron transport network is a key factor determining electron transport and device stability, with polymeric acceptors likely to establish such a network.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

A nanofluidic intracellular delivery (NanoFLUID) patch provides a versatile, biocompatible and efficient method for the targeted delivery of payloads to internal organs for therapeutic purposes and for biomolecular investigations.

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.

Immune checkpoint blockade is an effective therapy in melanoma, but response is highly variable between patients. Here, the authors show that Inducing co-stimulatory immune checkpoint CD137L expression in melanoma cells enhances T cell-mediated anti-tumor immunity.

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.

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.

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.

Anti-TSLP biologics have shown promise for the clinical treatment of type 2 respiratory disease. Here the authors present a clinical trial of CM326, a monoclonal antibody against TSLP, and show the clinical effects in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), who present with type 2-dominant inflammation.

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.

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.

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.

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.

High-resolution satellite observations reveal that large lakes on the Tibetan Plateau have total nitric oxide emissions comparable to anthropogenic emissions from individual megacities worldwide.

The conventional focus on pore size distribution overlooks the role of surface charge homogeneity in ion separation by polymeric membranes. This study proposes a surface charge engineering strategy for fabricating highly ion-selective membranes.

ATP/ADP translocators in obligate intracellular parasites and plastids facilitate energy parasitism and endosymbiosis by mediating ATP import and ADP export, with their cryo-EM structures and mechanisms revealed, providing insights for drug development against intracellular pathogens.

Molecular assembly is of great importance in many fields. Here, the authors establish a strategy to post-modulate angle-mismatched layer-by-layer materials by fullerene derivatives and achieve a modulation accuracy of up to 5 Å.

Néel spin-orbit torques arise due to charge currents in some antiferromagnets, and have sparked interest as a possible pathway for achieving electrical control of antiferromagnetic order. While the driving of antiferromagnetic order by Néel spin-orbit torques is now experimentally well established, the inverse process, where magnetic excitations in an antiferromagnetic drive a charge current is not reported. Here Huang, Liao, Qiu, and coauthors observe this inverse process in an Mn2Au thin film.

By controlling the flow or composition of liquids, optofluidics provides numerous possibilities for devices, and so has great potential for transformation optics. Here, a multi-mode optofluidic waveguide is presented, which manipulates light to produce controllable chirped focussing and interference.

3D higher-order topological insulators (HOTIs) exhibit 1D hinge states depending on extrinsic sample details, while intrinsic features of HOTIs remain unknown. Here, K.S. Lin et al. introduce the framework of spin-resolved topology to show that helical HOTIs can realize a doubled axion insulator phase with nontrivial partial axion angles.

In this phase 3 trial, first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with anti-PD-1 finotonlimab plus cisplatin plus 5-fluorouracil (C5F) prolonged overall survival compared with placebo plus C5F.

Hanging Coffins were a mortuary tradition practiced in southern China and Southeast Asia. Here, the authors show that different groups of ancient Hanging Coffin practitioners are genetically related, and that they are ancestors of present-day Bo people.

Memristor arrays based on molecular crystal with van der Waals-linked cages are fabricated, enabling ultralow energy switching, high endurance and seamless integration into neuromorphic computing hardware.

Computational analysis and pairwise assays reveal that bacterial topoisomerase IV is a target of microbially produced phenazines, which informs synthetic-community design to treat fungal crop infection.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.