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Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Here the authors reveal that the prostate cancer risk variant rs4519489 enhances binding of the oncogenic transcription factor USF1, upregulating NOL10. Elevated NOL10 promotes tumor progression, highlighting the rs4519489–USF1–NOL10 axis as a potential biomarker and therapeutic target.

Vasomotor function is regulated by the autonomic nervous system, but its electrophysiological basis remains poorly captured, especially post-stenting. Here, the authors develop a bioadhesive bioelectronic interface for precise monitoring and modulation of vasomotor activity.

Here the authors reveal how an incoherent feedforward C/EBPα–Notch circuit times lung cell fate, guiding alveolar development, repair after injury, and shifts between protective and reparative states.

This study reports that the gene SMPED1, located in a previously identified dichogamy-determining region in Alpinia species, controls the timing of sex-organ synchrony, improving our understanding of the evolutionary mechanisms of plant sexual diversity.

A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

A genome-wide CRISPR screen helps to identify the Epstein–Barr virus receptor desmocollin 2 for primary epithelial cell infection. Additional infection assays revealed that desmocollin 3 also aids infection.

High-density multimodal soft bioelectronic fibres provide a platform for minimally invasive implantable electronics, where diverse sensing and stimulation functionalities can be effectively integrated.

Ni, Wei, Vona and colleagues use human brain organoids to dissect patient AIRIM variants associated with neurodevelopmental features. A subset of variants impaired ribosome production and protein synthesis, and delayed radial glial cell specification.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Cryogenic electron microscopy structures and functional analyses reveal that NCLX functions as a H⁺/Ca²⁺ rather than a Na⁺/Ca²⁺ exchanger, and uncover its transport mechanism with implications for therapies treating cardiac and neurodegenerative disorders related to abnormal mitochondrial Ca²⁺.

UTe₂ is a proposed intrinsic topological superconductor, but its quasiparticle surface band has not yet been visualized. Now this is achieved using quasiparticle interference imaging, revealing the symmetry of the superconducting order parameter.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

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.

The majority of human genes can produce multiple isoforms, but studying their functional relevance requires tools to target specific isoforms. Here, the authors develop a CRISPR-based exon-exon junction-targeting strategy to achieve isoform-specific RNA knockdown.

Hachem et al. show that AMPAR signaling drives the acute activation of ependymal-derived neural stem/progenitor cells after spinal cord injury and that this mechanism can be targeted therapeutically to harness the endogenous regenerative potential of the spinal cord.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Bone marrow adipose tissue accounts for almost 10% of human fat mass, but its roles remain unclear. Here, Xu et al. identify more than 45 diseases linked to marrow adiposity in over 48,000 people, including causal roles in musculoskeletal disease.

Mitotic DNA synthesis (MiDAS) has been proposed to utilize break-induced DNA replication, a form of homology-directed DNA repair (HDR). Here, the authors find that core DNA end-resection factors required for HDR, including MRE11, CtIP and BRCA1, and a RecQ family helicase, WRN, are essential for MiDAS.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

Ribonucleoprotein aggresomes exclude ribonucleases and protect mRNA to promote rapid translation reactivation and cellular recovery after stress alleviation in Escherichia coli.

Akincilar, Fidan et al. report a conserved role for telomerase reverse transcriptase in regulating inflammation via the cGAS–STING nucleic acid-sensing pathway in myeloid cells, independent of its telomerase activity.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Chen et al. use UK Biobank data to reveal a dietary pattern associated with a lower risk of dementia, and validate this in additional cohorts.

CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human gastric 3D organoids, also integrating single-cell CRISPR screens, to identify genes involved in the response to cisplatin in gastric cancer.

The spin Hall effect and its inverse allow conversion between charge and spin currents in both magnetic and nonmagnetic materials. Weiet al.observe an anomaly in the temperature dependence of the inverse spin Hall effect, which suggests that it can also be used as a sensor for very small magnetic moments.

SARS-CoV-2 rebound is a recurrence of symptoms or return to test positivity after initial recovery. Here, the authors demonstrate an association between SARS-CoV-2 rebound and post-acute COVID conditions using data from Hong Kong.

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.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

High-entropy nanocarbides (HENCs) containing 5–22 metal elements are synthesized through a nanoconfined impulse synthetic strategy enabled by Joule heating-induced in situ reactions in carbon nanotube films. These HENCs exhibit multi-element effects and enhanced electrocatalytic activities due to their nanoscale size and modified catalytic sites.

A spin current is injected from a ferromagnet into a nonmagnetic metal at magnetic resonance. Here, the authors show that this current has both a direct-current and a much larger alternating-current component, indicating that these structures could be useful for high-frequency spintronics.

By regulating the level of accessible cholesterol on endothelial cells via OSBP/ORP-mediated transport, tetraspanin tunes the balance of Cdc42 and RhoA activities to affect vascular inflammation. Reducing accessible cholesterol by statin treatment or blocking its non-vesicular transport by OSBP/ORP inhibition can limit vascular inflammation.

The oxygen reduction reaction (ORR) is limited by the scaling relationship in the conventional oxygen associative pathway. In this study, single p-block atoms and interstitial H are incorporated into Pd metallenes favoring the direct dissociation mechanism, leading to high alkaline ORR performance.

Parity-time symmetry breaking and related non-Hermitian phenomena, such as high-order exceptional points, have attracted significant interest across various experimental platforms. Here the authors demonstrate a third-order exceptional point induced by parity-time symmetry breaking in a dissipative trapped ion.

Asymmetric hydrophosphorylation of unsaturated compounds is a straightforward and atom-economic approach to obtaining chiral organophosphorus compounds. Herein, the authors describe a Pd-catalzyed ligand controlled regiodivergent and enantioselective hydrophosphorylation of styrenes.

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.

High-mass-loading electrodes are essential for high-energy all-solid-state batteries but suffer from poor kinetics. Here, authors use neutron imaging to identify ion-transport limitations and introduce a gradient solid electrolyte design that improves battery mass-loading and rate performance.

The retreat of the Fennoscandian Ice Sheet during the last deglaciation led to the infiltration of seawater into a submarine groundwater system on the Norwegian continental shelf, according to an analysis of groundwater geochemistry on the Norwegian shelf.

Semiconductor quantum dots that simultaneously support blue and yellow emission offer a route to realizing efficient white light-emitting diodes.

Previous ophthalmic foundation models have struggled to generalize effectively to diverse and rare fundus diseases, restricting their clinical applicability. Here, the authors introduce a vision-language foundation model that demonstrates superior performance in diagnosing both common and rare fundus conditions.