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Bardeesy and colleagues show that mutant GNAS suppresses salt-inducible kinases by activating PKA, leading to lipid remodelling and pancreatic tumourigenesis

Parathyroid hormone (PTH) is an endogenous hormone and osteoporosis therapeutic that suppresses sclerostin activity. Here the authors develop SIK inhibitors as potential therapeutic tools and use them to show that PTH-cAMP signalling in osteocytes inhibits SIK2 from driving Hdac4/5 nuclear shuttling to suppress sclerostin.

Caterina Iorio et al. use a high-throughput RNAi screen to identify the GPR3-SIK2-CDKN1B axis as key players involved in regulating pancreatic beta cell proliferation. These results suggest that GPR3 and SIK2 are both potential targets to stimulate regeneration of beta cells in diseases like type 1 diabetes.

Jeong-Sik Oh hikes to find hidden fault lines, with the help of drones, aircraft and laser technologies.

Screaton and colleagues delineate a pathway involving the AMPK-related Sik2 kinase using mouse models. They show that Sik2-mediated phosphorylation and subsequent degradation of CDK5R1 (p35) by PJA2 is needed for glucose-induced insulin secretion and β-cell functional compensation in models of hyperglycemia and obesity.

A combination of single-cell approaches, lineage tracing and metabolomics is used to characterize the changes to intestinal stem cell function in the small intestine that underlie intestinal maladaptation in mice fed an obesogenic diet.

The kinase Lkb1 is expressed in various metabolic tissues and is known to regulate cellular and systemic energy homeostasis. Here, the authors delete Lkb1 specifically in mature adipocytes of mice to show that Lkb1 regulates brown adipose tissue expansion and expression of UCP1.

Unsatisfactory long-term stability of solid-state Li-metal batteries is hampering their commercialisation despite their potential high energy density. Here, authors employed a rationally designed porous tellurium interlayer and demonstrated high capacity retention for 4000 cycles.

Twenty years have passed since the first small-molecule protein kinase inhibitor, imatinib, gained FDA approval. Here, Cohen et al. review advances in improving the potency and specificity of small-molecule protein kinase inhibitors and assess approaches to overcome the challenge of drug resistance. Applications of these compounds in cancers and other disorders, as well as future directions in the field, are discussed.

Lasing with multi-pass gain is achieved in a diamond-based X-ray cavity at the European XFEL, opening a path to next-generation X-ray science.

To reach terabit density in random access memory devices, the select switching and storage components need to be improved. Here, the authors fabricate a fully stackable switching device based on chalcogenides, which reaches an exceptional performance following reactive nitrogen and nitrogen plasma treatments.

Small cell lung cancer (SCLC) is aggressive with limited therapeutic options. Here, authors find that loss of CRACD induces neuroendocrine plasticity and immune evasion and suggest manipulating the CRACD-EZH2-MHC-I axis as a potential therapeutic strategy for SCLC.

Molybdenum disulphide offers some tantalizing advantages over graphene as a material with which to fabricate field-effect transistors. Kimet al. present a comprehensive study of field-effect transistors made from multilayer samples of MoS₂and find that they can achieve high carrier mobilities.

Scaling effects on ferroelectric domains could impact applications for next-generation miniaturized devices. Here brownmillerite oxides are shown to demonstrate ferroelectric domains with widths down to the sub-unit-cell level.

LKB1-mut has been shown as a major genetic driver of primary resistance to immune checkpoint inhibitors. Here this group reports the identification of the LKB1-IAP-JAK dynamic complex as a molecular determinant for immune response of LKB1-mut lung cancer cells.

Researchers identified three distinct white matter hyperintensity progression patterns, validated in both patients and healthy individuals. Each pattern links to different vascular risks and outcomes, improving stroke prediction.

Stable coating of filters with a thin liquid layer enhances adhesion of airborne particulates while maintaining high air permeability, resulting in longer lifetimes and higher efficiency of these filters.

A screen for host factors involved in late steps of the reovirus life cycle identifies the TRiC chaperonin as essential for outer-capsid protein folding, and thus for incorporation onto progeny virions, assembly and virus production.

Tumour evolution and heterogeneity of recurrent meningioma tumours remains to be explored. Here, the authors perform single nuclei sequencing of matched primary and recurrent meningiomas and reveal diverse cellular compositions and hierarchies.

Using the European XFEL free-electron laser, researchers demonstrate terawatt-scale, attosecond hard X-ray pulses. Ten pulse trains per second, each containing hundreds of pulses at megahertz repetition rates, are achieved. Such short and intense pulses at high repetition rate enable unprecedented damage-free X-ray measurements with attosecond temporal resolution.

Despite advances in ctDNA cancer detection, early detection remains difficult. Here, the authors utilise whole genome sequencing of 2,125 patient samples to create a model for early cancer and tissue of origin detection.

Quantifying water sustainability relies on limited and non-uniform metrics that risk greenwashing and hinder effective investment decisions. To address this, the proposed water sustainability index (WSI) offers a transparent, quantitative framework that accounts for water withdrawals, discharges, consumption, reuse and watershed stress to guide cost-effective sustainability improvements.

The cyclic AMP-responsive element-binding protein (CREB) is phosphorylated in response to a wide variety of signals, and it functions in concert with cAMP-regulated transcriptional co-activators (CRTCs). CREB and CRTCs mediate the effects of fasting and feeding signals on the expression of metabolic programmes in insulin-sensitive tissues.

Group BStreptococcuscauses meningitis in newborn infants but how the bacterium crosses the blood-brain barrier is unknown. Here, the bacterial pili adhesion molecule, PilA, is shown to bind to collagen and promote binding of the bacteria to integrins expressed on the blood-brain endothelium.

Mitsiades and colleagues utilize functional genomics data in over 700 cancer cell lines, to identify genes with preferentially essential functions in multiple myeloma, which may represent targets for precision medicine strategies.

A comprehensive cell atlas of the aged prefrontal cortex identifies two distinct cellular trajectories of ageing driven by specific glial and neuronal subpopulations, some of which are associated with clinicopathologic traits that define Alzheimer’s disease.

Seo et al. present an approach to regulate the formation and optoelectronic quality of the SnO₂ electrodes, improving electroluminescence and efficiency in perovskite solar cells.

This Review discusses recent advances in interlayer engineering for perovskite solar cells, highlighting promising materials and architectures that could improve the stability and efficiency of devices.

Wireless bioresorbable stimulators are promising therapeutic implants that naturally dissolve after use. Here, the authors developed a device that operates for months and enables simultaneous multi-site stimulation, preventing early muscle atrophy and accelerating reinnervation in nerve injury models.

This study reports the direct 3D quantitative mapping of local nitrogen distribution across a range of silicon-based semiconductor structures and devices using atom probe tomography, offering nanoscale insights into impurity control and contributing to improved device performance and reliability.