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Diazo compounds are invaluable intermediates in organic synthesis, however, traditional C–H diazotization methods often face environmental and safety challenges due to the use of azide compounds and excessive acid/base. Here, the authors introduce a protocol using 2-methoxyethyl nitrite, achieving efficient diazotization of 2-substituted indoles with high reactivity and selectivity.

The structure of human prostaglandin E receptor EP4 in complex with antagonist ONO-AE3-208 and a functional antibody reveals a ligand-binding site at the interface of the lipid bilayer that is unique among GPCRs.

In the observational SCRUM-Japan GOZILA study, after a median follow-up of 11 months, patients with metastatic gastrointestinal tumors who received biomarker-matched therapies based on circulating tumor DNA profiling showed a greater clinical benefit than those receiving unmatched therapy.

Previous studies have shown the importance of unidirectionally aligned domain nucleation for the growth of 2D semiconductor single crystals. Here, the authors report the observation of a self-alignment process of misoriented domains during the metal-organic chemical vapour deposition growth of 2D MoS₂ on sapphire, leading to single-crystalline films with improved carrier mobility.

This prospective study conducted in a phase 3 trial has shown that pre-treatment serum VEGF-A was a negative biomarker for PFS in patients with advanced NSCLC treated with a combination of an anti-angiogenic agent and a PD-1 axis inhibitor.

A large cross-population atlas of gene–environment interactions reveals how age, sex and lifestyle shape genetic effects, heritability, prediction accuracy and disease biology, with implications for personalized medicine and drug development.

A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Mitochondria with mutations in their DNA from cancer cells can be transferred to T cells in the tumour microenvironment, which leads to T cell dysfunction and impaired antitumour immunity.

The tooth root is a critical component of the tooth. Here they identify root-forming CXCL12+ apical papilla progenitor cells that provide odontoblasts and cementoblasts in a Wnt-dependent manner, with plasticity to form alveolar bone osteoblasts during regeneration.

A newly identified bacterial strain (YB328) isolated from the faeces of patients who responded to immune checkpoint blockade therapies can promote antitumour immunity through the activation of tumour-specific CD8⁺ T cells.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Retinitis pigmentosa is a genetic disease causing degeneration of retinal pigment epithelial and photoreceptor cells. Here, the authors show that PNPLA6 regulates choline metabolism for retinal homeostasis, and its dysfunction leads to degeneration, which can be rescued by choline supplementation.

The alveolar bone supports the tooth’s lifelong functionality. Here, the authors identify a tooth-specific mechanism of bone formation in which the Hedgehog–Foxf pathway regulates the alveolar bone osteoblast fates of DF progenitor cells.

Spin current carrying angular momentum enables intriguing phenomena and many fascinating applications. Here the authors demonstrate that thermally driven spin Seebeck current can give rise to the mechanical torque when transmitting through a Y₃Fe₅O₁₂ micro cantilever.

In aged mice, inhibition of prostaglandin E₂ (PGE₂) signalling through its receptor EP2 improves cellular bioenergetics, reduces inflammatory responses and restores hippocampal plasticity to youthful levels, resulting in an improvement in spatial memory and cognition.

This study identified a new class of skeletal stem cells in the endosteal space of bone marrow, which are abundant in young bone marrow, express Fgfr3 with osteoblast-chondrocyte transitional identities and can turn into bone tumor-making cells.

Sekiya and colleagues identify that, in response to reductive metabolism, CtBP2 is secreted via exosomes and regulates metabolism in recipient cells via CYB5R3 and AMPK. Exosomal CtBP2 administration extends lifespan and healthspan in aged mice, and serum levels of CtBP2 decline with age in humans.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

The multicenter phase 2 TRIUMPH trial shows the utility of ctDNA genotyping as a screening platform to select patients with HER2-amplified metastatic colorectal cancer who benefit from dual-HER2 blockade with trastuzumab and pertuzumab

Bone marrow stromal cells (BMSCs) lining sinusoidal blood vessels are mesenchymal cells whose function is critical for the skeleton. Here the authors show that quiescent CXCL12-expressing BMSCs can convert into a skeletal stem cell-like state, and differentiate into cortical bone osteoblasts only in response to injury.

Defects in cell division occur often in early embryos, though the mechanisms underlying these errors and their correction remain unclear. Here they develop a method for imaging zygotic chromosomes during human zygotic cleavage and find that the spindle shape influences formation of micronuclei.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

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.

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. Here they show that perichondrial cells are destined to become adipocyte-biased stromal cells, indicating that marrow stromal compartments are defined by their cells of origin.