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In a randomized, double-blind, placebo-controlled trial comparing autologous mRNA-engineered BCMA-targeting CAR T cell therapy versus placebo in patients with generalized myasthenia gravis, a significantly higher percentage of patients exhibited a reduction in disease activity in the treatment arm than in the placebo arm.

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.

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.

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.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

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.

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.

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.

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.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Cells must sense heat quickly to protect their proteins and membranes. Here, the authors show that membrane stretch detected by the membrane sensor Mid2 promotes rapid phosphorylation of the Hsp70 chaperone to coordinate gene activity, protein synthesis and resolution of stress-induced protein droplets during heat shock.

Generation of orbital currents in a non-magnetic material can be useful to build efficient orbitronic devices. Now, the interplay of chiral phonons and electrons is shown to produce orbital currents in α-quartz.

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.

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

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.

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.

Three BRAF inhibitors are used to treat melanoma and colorectal cancer. Here, the authors demonstrate that these drugs bind and activate the protein kinase GCN2, a previously unappreciated off-target effect that may modulate tumour cell responses.

Carbonate-based electrolytes can impart advantages in lithium sulfur batteries, but performance is often limited by incompatibility with sulfur-based cathodes. Here the authors elucidate a mechanism for conversion of sulfur to lithium sulfide and demonstrate improved performance in a Li-S cell.

Hexacoordinate silicon is seen often in molecular compounds, but very rarely in crystalline silicate materials. Now, reversible Si–O chemistry has been used to assemble octahedral dianionic SiO₆ building units and anthracene derivatives into crystalline microporous silicate organic frameworks that share characteristics of both covalent organic frameworks and inorganic zeolites.

Semaglutide, a GLP-1 receptor agonist, may offer neuroprotective benefits after stroke, but its effects in large vessel occlusion (LVO) are unknown. Here the authors show, in a phase 2 randomized trial, that semaglutide is safe after endovascular therapy and may improve recovery in patients not receiving intravenous thrombolysis.

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.

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 existence of phosphatases specialized in regulating the axon initial segment (AIS) was unclear. Here, the authors show that a PP2A-B55 subunit is selectively enriched at the AIS and contributes to its local phospho-regulation.

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.

Despite its importance in lithium batteries, the mechanism of Li dendrite growth is not well understood. Here the authors study three representative solid electrolytes with neutron depth profiling and identify high electronic conductivity as the root cause for the dendrite issue.

Natural products and their synthesis have always fascinated organic chemists, frequently providing the inspiration and testing ground for new synthetic methods. This Review considers examples of natural products that were prepared first synthetically and predicted to be natural products prior to their isolation from nature.

Asymmetrical distribution of tau pathology in Alzheimer’s disease is linked to asymmetrical amyloid-beta deposition, not reduced brain connectivity, suggesting regional vulnerability plays a key role in determining the distribution of tau pathology.

Human-operated optimization of non-aqueous Li-ion battery liquid electrolytes is a time-consuming process. Here, the authors propose an automated workflow that couples robotic experiments with machine learning to optimize liquid electrolyte formulations without human intervention.

Hydrogen sulfide (H₂S) reversibly modifies low molecular weight and protein thiols to form persulfides (RSS⁻) and polysulfides (RS(S)nS⁻) for antioxidant defence and regulation of activity. Here, the authors report a sensitive LC-MS/MS procedure that separately traps and quantifies the sulfur atom of H₂S, the terminal sulfur atom of RSS and RS(S)nS-, and the internal sulfur atoms of RS(S)nS ⁻ as diagnostic products in biological samples.

Fast-charging is highly desired for lithium-ion batteries but is hindered by potential hazardous lithium plating and the associated parasitic reactions. Here, the authors report a nondestructive differential pressure sensing method for early detection and mitigation of lithium plating in fast-charging batteries.

Budding yeast use multilayered regulation by Ait1, Gcn2, and the SEAC/GATOR complex to control TORC1 activity. This circuit design ensures that cells can adapt to low-quality nitrogen sources or shut down growth during starvation.

A randomized controlled trial found that eliminating opioids after minimally invasive gynecologic surgery did not compromise pain control at postoperative day 1, with similar pain scores and recovery outcomes between opioid-free and restrictive opioid groups up to day 7.

Designing electrode architectures for Li-ion batteries that can be reversibly accessible for ion storage can be challenging. Using operando techniques the mechanistic origin of lithiation-induced phase transformations in a V₂O₅ model cathode is now clarified.

Somatic instability plays a role in Huntington’s disease. Here, the authors show that lowering HTT levels by transcriptional repression suppresses somatic instability. This can also be done without affecting HTT levels by direct CAG repeat binding.

Chemically induced protein degradation is a powerful alternative to classical inhibition, but some proteins have deeply masked binding pockets that make the development of degrader molecules difficult. Here, the authors discover an alternate site on nuclear receptors that can be targeted by degraders.

STING–type-I interferon pathway regulates the immunogenicity of several cancer types, including head and neck squamous cell carcinoma. Here the authors describe that glutamine metabolism in the tumour microenvironment dampens the STING–type-I interferon pathway by epigenetically silencing the expression of BATF2, which functions as a tumour suppressor.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Myeloid derived suppressor cells (MDSC) use different metabolic mechanisms to adapt to the tumour microenvironment. Here the authors show that 6-phosphogluconate dehydrogenase (6PGD) is important for MSDC function and that blockade of 6PGD impaired MDSC function and suppresses tumour growth leading to metabolic and functional changes in the MDSC and a more pro-inflammatory phenotype.

Analysis of dendrite initiation, owing to filling of pores with lithium by means of microcracks, and propagation, caused by wedge opening, shows that there are two separate processes during dendrite failure of lithium metal solid-state batteries.

This paper uses a multi-region model to show that single-region models used by thousands of companies to estimate CO2 emissions related to goods they purchase may drastically underestimate and misidentify the largest sources of upstream emissions.

Fast panoramic rotational ultrasound tomography and photoacoustic tomography are integrated for hybrid rotational ultrasound and photoacoustic tomography, for three-dimensional dual-contrast imaging of soft tissue and vasculature across the human body.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.