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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.

Light and temperature provide critical information guiding developmental transitions in plants. This study shows that blue light signals via PHOT2 and low temperature signals via CAMTA2 are linked, transducing a combined signal regulating flowering.

A 1,024-channel microelectrode array is delivered to the brain cortex via a minimally invasive incision in the skull and dura, and allows recording, stimulation and neural decoding across large portions of the brain in porcine models and human neurosurgical patients.

Mutation of conserved prolines enhances correct pairing of light and heavy chains for bispecific IgG-like antibody production.

N-type sulfides are attractive solar-to-hydrogen photocatalysts but have faced challenges with overall water splitting. Here, the authors report that tailored surfaces and cocatalysts enable sulfides to achieve efficient, stable, and safe production of separate streams of stoichiometric hydrogen and oxygen.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

Nonreciprocal quantum effects can unlock unique quantum resources but unidirectional quantum synchronization has been overlooked. Here authors demonstrate robust one-way quantum synchronization of phonons, overcoming imperfections and noise via combined Sagnac and magnon Kerr effects.

Reframing of arousal as a latent dynamical system can reconstruct multidimensional measurements of large-scale spatiotemporal brain dynamics on the timescale of seconds in mice.

Desmosomes are adhesive junctions in tension prone tissues. Here, the authors show that cytoskeletal forces alter the conformation of desmoplakin, a key desmosomal protein, and propose this may enable the desmosome to sense and respond to mechanical stimuli.

Using visible-light-induced crosslinking, a local stiffening approach is developed for ex vivo mouse and human lung tissue as an early lung injury model, directing epithelial cell mechanosensing, differentiation and nascent protein deposition.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

The SWEET project is a multicenter, randomized, controlled trial that shows that long-term consumption of sweeteners and sweetness enhancers improves body weight control and elicits beneficial gut microbiota changes in adults with overweight or obesity.

Endosomal sequestration of lipid-based nanoparticles is a barrier to delivery of nucleic acids. Here the authors test an array of cholesterol variants and perform in-depth investigation of nanoparticle shape, internal structure and intracellular trafficking.

Skin prick testing for allergy diagnosis is limited by variability due to differences in test setting and operator expertise. Here, the authors develop and validate an AI-assisted readout method for reading allergy skin test results, and find that integrating AI enhances standardization throughout the skin prick testing process.

Myocardial contractile force and intracardiac hemodynamic shear stress coordinate the initiation of trabeculation in heart development. Here, the authors report that radially aligned myocardial strain activates snai1b⁺/Notch⁻ cardiomyocytes, initiating delamination for trabeculation.

In response to declining vaccination coverage in England the recommended age for the second vaccine dose has been changed from 40 months to 18 months. Here, the authors perform a mathematical modelling study to assess the impacts of this change on measles transmission dynamics.

The treatment potential of psilocybin for postpartum depression was investigated in a preclinical mouse model. Here the authors show both acute and long-term effects of psilocybin in mothers and their offspring who were exposed via lactation.

BamA is the catalytic core of the BAM complex, which inserts proteins into bacterial outer membranes. Here, the authors show that hinge flexibility between BamA’s β-barrel and POTRA domains is vital, demonstrating how evolution has fine-tuned the BamA sequence and structure for function.

A fresh approach to protein design that incorporates excited intermediate states enables precise control over the lifetime of protein interactions, with potential applications in cell-signalling modulation and in biosensors and synthetic circuits.

Comparison between structures of human, mouse and rat P2X7 receptors define ortholog-specific pharmacology and facilitated structure-based drug design of UB-MBX-46, an antagonist that selectively inhibits the human P2X7 receptor with sub-nanomolar potency.

The pressures faced by lab leaders to be excellent researchers, teachers, managers, accountants and mentors can exact a heavy toll.

Observations of SN 2021yfj reveal that its progenitor is a massive star stripped down to its O/Si/S core, which remarkably continued to expel vast quantities of silicon-, sulfur-, and argon-rich material before the explosion, informing us that current theories for how stars evolve are too narrow.

Robots benefit from touch perception, but sensing multi-directional forces is challenging. Here, the authors introduce a theory using taxel value isolines for superresolution sensing, improving sensor design and performance under shear forces.

iExoKras^G12D are engineered exosomes for the delivery of siRNA targeting KRAS^G12D. Here the authors describe the results of a phase I trial of iExoKrasG12D in patients with metastatic pancreatic cancer, reporting safety and clinical activity, as well as immunological correlates informing on tumor immune microenvironment reprograming and future combination with immune checkpoint inhibitors.’

The direct contribution of aberrant epithelial cells to lung fibrosis is largely unknown. The authors use murine and human systems to identify how these cells activate fibroblasts, and how reciprocal signals cause them to enter a profibrotic state.

The Akt-mTOR axis influences cell activation, differentiation and metabolism. Jordan and colleagues show that thymic and inducible T_H17 cells exhibit different requirements for mTORC1 and mTORC2 as well as Akt isoforms.

Analysis of human Robertsonian chromosomes originating from 13, 14 and 21 reveal that they result from breaks at the SST1 macrosatellite DNA array and recombination between homologous sequences surrounding SST1.

Debio 1453, a FabI inhibitor, shows potent activity against antibiotic-resistant Neisseria gonorrhoeae, rapidly killing bacteria in vitro and clearing infection in mice, supporting its potential for treating drug-resistant gonorrhoea.

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.

Al-Hilal, Chrysovergi et al. identify a role for durotaxis in lung fibrosis and metastatic pancreatic cancer, mediated by the FAK–paxillin mechanosensor complex, and demonstrate therapeutic targeting of this pathway using the small molecule JP-153.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Ricca et al discover a new family of tubular pili in Microcystis aeruginosa, a harmful algal bloom-forming cyanobacterium. These pili are crucial for buoyancy by forming cell micro-colonies, which increases drag and prevents sinking. The pili also enrich microcystin and co-localize with iron-enriched extracellular matrix components, suggesting a vital role in bloom proliferation.

This study discovered that locally confined DNA differences boost crossover rates in both Arabidopsis and maize, revealing a conserved mechanism that can accelerate plant breeding and trait introgression.

Our basic understanding of neuromodulation in the claustrum remains limited. Here Madden et al., identify a key mechanism by which serotonin and the psychedelic psilocybin modulate cortical signalling through the claustrum, a brain region involved in regulating cognition and brain network states.

The authors enable recording of circuit-scale neuronal voltage dynamics at > 5 kHz sampling rate by using an acquisition pipeline for voltage imaging that assigns each region of interest to a single pixel in the detector, enabling optimally compressed acquisition of intensity traces.

This study demonstrates dark-mode engineering as a powerful tool to achieve switchable topological phonon transfer and blockade, offering a versatile approach to robust, scalable phononic control for quantum information processing.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

The role of wild and domesticated animals on alpine ecosystems is unclear. Here, the authors use sedaDNA from 14 European alpine lakes to demonstrate a positive association between wild and domesticated animal and plant diversity through the past 14 thousand years.

The native anaplastic lymphoma kinase (ALK) oncofetal protein is expressed in neuroblastoma and in multiple pediatric and adult solid tumors. Here, the authors show an ALK-directed antibody-drug conjugate with therapeutic efficacy in ALK-expressing preclinical models.

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.

Adherens junctions (AJs) mediate cell-cell adhesion between epithelial cells but tools to study their dynamic regulation are lacking. Here the authors develop an optochemical tool to stimulate the assembly of AJs through addition of a photocleavable tool and their dissociation upon exposure to light.

The SARS-CoV-2 Nucleocapsid (N) protein serves multiple roles in the viral lifecycle. Phosphorylation toggles N between these roles by altering N’s conformation, its material properties when phase separated with RNA, and its membrane interactions.

Researchers with lived experience of the chronic workplace stress that typifies burnout describe how they sought help and turned their working lives around.

Cryptosporidium is an important threat to public health, yet it lacks a robust genetic toolkit. Here, Watson et al. introduce a targeted CRISPR-based screening method to identify parasite genes that are essential for its survival within the intestine.

To stop bleeding from an injured vessel, platelets adhere and form a clot despite high shear stress from the flow. Here, the authors show that platelet actin disassembly is a key step that enables a receptor to translocate to membrane lipid rafts, enhancing its adhesive function under shear stress.

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.

Super spreading events are considered important contributors to the spread of COVID−19, but the extent to which superspreading varies by transmission setting is unclear. Here, the authors demonstrate heterogeneity in superspreading and the generation interval between COVID−19 cases in different settings using data from Hong Kong.