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Epstein–Barr virus (EBV) is a widespread herpesvirus linked to cancer and autoimmune disease. The authors in this work design and characterize a stabilized prefusion form of gB, an essential viral fusion protein, advancing EBV vaccine and therapeutic development.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

Chronic Kidney Disease affects 1 in 10 people worldwide with prevalence continuing to rise, thus there is a need to identify novel biomarkers that can add value to existing clinical and biochemical risk predictors. Here the authors identify miR190a-5p as potential indicator of kidney health and disease progression in patients with chronic kidney disease.

Pure-water anion-exchange electrolysis is hindered by fragile ionomers and delaminating catalyst layers. Here, the authors report covalently anchoring catalysts within a cross-linked ionomer network, yielding a pure-water cell that delivers 2.55 A cm⁻² at 1.9 V and runs over 1,800 h.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Here, the authors report magneto-mechano-electric energy generation based on Mn-doped PIN–PMN–PT single crystals. Their device provides sufficiently high and stable output power density for efficient self-powered operation of wireless IoT systems and other large-scale energy harvesting applications.

Sivanandan, Leitmann, and colleagues present the CellPaint-POSH platform, which combines pooled CRISPR screening with Cell Painting. Using self-supervised deep learning on cell images, the method enables discovery of gene function and biological networks.

Targeting incretins is emerging as an effective approach to treat cardiovascular–kidney–metabolic syndrome. Here, the authors examine the biological effects of incretins and other metabolic hormones, such as glucagon and amylin, as well as discussing current clinical data demonstrating the organ-protective effects of incretin drugs and their potential underlying mechanisms.

Combination immunotherapy approaches might be effective in inducing sustained control of HIV by slowing rebound and improving CD8⁺ T cell responses.

The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

Here the authors introduce INSPECT, a live-cell imaging method for mapping protein interactions. They reveal how Cdc42–FMNL locks cell polarity while Rac1–ROCK triggers turning, exposing the intrinsic program that drives spontaneous cell migration.

Hodgkin Reed Sternberg (HRS) cells and their surrounding microenvironment in Hodgkin lymphoma remain poorly characterized. Here, the authors perform genome-wide transcriptional profiling with spatial and single-cell resolution to explore the cellular and molecular composition of the Hodgkin lymphoma microenvironment and used machine learning to identify IL13 as a potential HRS cell survival factor.

HMGCR is upregulated by E2F1, driving ferroptosis resistance by reducing oxidative damage triggered by T cell-based therapy. Notably, targeting HMGCR restores ferroptosis sensitivity in immune-refractory tumors, enhancing response to PD-1 blockade as well as adoptive T cell transfer therapy.

The authors report the discovery of charge order with onset temperature of 800 K in the kagome superconductor YRu₃Si₂. In addition, they observe time-reversal symmetry breaking below 25 K, field-induced magnetism below 90 K and bulk multi-gap superconductivity below 3.4 K.

Here, the authors identify the microbiota-derived corisin as a driver of diabetic kidney fibrosis via cellular aging and show that targeting corisin with a monoclonal antibody alleviates disease in mice, suggesting a potential therapeutic avenue.

In patients with hormone receptor positive, human epidermal growth factor receptor 2-negative (HR+/HER-) breast cancer, endocrine therapy is standard of care but resistance often occurs. Here, the authors report a phase I trial investigating the ER degrader, AC699, in patients with locally advanced or metastatic ER+/HER2- breast cancer.

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.

Animal models of drug use require specialized technical expertise and often differ from how humans consume drugs. Here, the authors establish a robust method which allows mice to self-administer intranasal cocaine, greatly improving face validity and ease of use.

In the randomized phase 3 AMPLITUDE trial, patients with HRR-deficient mCSPC experienced longer progression-free survival when they were treated with niraparib and AAP compared to placebo and AAP.

Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate. Through integrated laboratory and clinical studies, the authors identify significant ERBB2 (the gene that encodes the HER2 protein) mutational heterogeneity in patients with urothelial cancer and co-mutation and amplification of ERBB2 as a potential biomarker of exceptional response to T-DXd.

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 global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Dry reforming of methane (DRM) offers a promising route to convert greenhouse gases into valuable syngas, yet its industrial application is limited by catalyst deactivation and carbon deposition under severe conditions. Here, the authors introduce a Ce-modified, Ni-exsolved perovskite catalyst that exhibits synergistic effects, enabling highly efficient and durable DRM performance.

Glioblastoma (GBM) is characterized by a high degree of heterogeneity and plasticity due to interplay with neural developmental programs. Here, the authors develop a model of GBM by introducing sequential oncogenic mutations in human neural stem cells and using this, identify INSM1 as a driver of a neural progenitor gene network promoting tumorigenesis.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Genetically encoded sensors are generally optimized to function during exponential growth rather than stationary phase, which limits their potential value for metabolic engineering and bioproduction. Here, authors engineer a stationary phase green light sensor and use pulsatile light to optimize production of industrially relevant small molecules.

The influence of spin–orbit coupling on itinerant electrons underlies the formation of spin–orbit Mott states. Here, the authors demonstrate a temperature-hysteretic cascade between charge-ordered phases stabilized by localized 5dspin–orbit Mott dimer states in metallic iridium ditelluride.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

The immune system undergoes significant changes with age. However, protein level characterization of these age-associated changes is limited. Here, the authors develop a machine learning (ML) model to predict changes in immune cell composition across different age stages based on CyTOF data on mouse CD45+ spleen cells and test the reliability of the ML model in predicting biological age using an obese mouse model, supporting the applicability of this tool to identify disease-related immune senescence.’

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Here, the authors perform a large GWAS for objectively quantified skin color in an East Asian population (N = 48,433), identifying potential causal genes, polygenic adaptations, and interaction between genetic variants and sun-exposure at polygenic level.

This large-scale cross-ancestry genome-wide association study reveals the genetic architecture of serum urate across ancestries and identifies urate-associated diseases and potential targets of urate-lowering drugs.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

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.

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

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.

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.

Early high-resolution images of two 2021 novae reveal eruptions unfolding in multiple stages with colliding outflows that produce shocks and gamma rays, reshaping our understanding of stellar explosions.

Mitochondrial DNA heteroplasmy associates with context-specific nuclear CpG methylation, supported by a cell model. Heteroplasmy–CpG scores relate to mortality and cardiovascular risk, though direction and mechanisms remain unclear.

In this Review, the authors discuss the physiological determinants of blood potassium levels, the health consequences of chronic hypokalaemia and hyperkalaemia, and the potential cardiorenal benefits of potassium supplementation. They also highlight strategies to reduce the risk of hyperkalaemia and enable patients with chronic kidney disease to consume a potassium-rich diet.