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Nicotinamide adenine dinucleotide (NAD) biosynthetic enzymes have been reported to be oncogenic. Here, the authors show that NAPRT, a key enzyme in the deamidated NAD biosynthesis pathway, functions as a suppressor of colon inflammation and tumorigenesis by maintaining DNA repair capability.

Visible-light-mediated intramolecular [2+2] cycloaddition of aza-1,6-dienes gives bridged, not fused, heterocycles, in violation of the ‘rule-of-five’, which dictates that five-membered rings are preferentially formed. This method allows a variety of bridged bicyclic scaffolds to be accessed, enabling drug-relevant properties to be readily tuned.

Cardiovascular risk is driven by genes, proteins, and metabolites, yet their combined predictive value is unclear. Here, the authors develop CardiOmicScore to integrate genomics, proteomics and metabolomics and predict six cardiovascular diseases up to 15 years prior to disease onset.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

Chen et al. report a tailored self-assembled monolayer to create a localized 2D/3D perovskite heterojunction. This strategy reduces interfacial loss, achieving photovoltages >90% of thermodynamic limit for wide-bandgap cells, and enables perovskite-organic tandem solar cells with efficiency of 27.11%.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The mechanisms underlying increased cardiometabolic risk from cancer treatment in childhood cancer survivors remain to be explored. Here, epigenome-wide analysis in childhood cancer survivors identified DNA methylation sites that mediate treatment-related cardiometabolic risks and are associated with inflammatory and metabolic pathways.

CRISPR–Cas9 in Streptococcus pyogenes prevents self-cleavage through abasic CRISPR RNA oxidations that suppress off-target activity. Inspired by a natural mechanism, Gu and Kim et al. designed chemically modified abasic guide RNAs to enhance genome-editing specificity of SpCas9, suppressing off-target toxicity in in vivo applications.

Current long acting HIV therapies face challenges like prolonged pharmacokinetic tails, which increase resistance risk. The authors develop dimeric bictegravir prodrug nanosuspensions that sustain therapeutic levels for six months with a short PK tail, supporting safer ultra-long-acting HIV treatment.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Doxycycline has been recommended as post-exposure prophylaxis for prevention of bacterial sexually-transmitted diseases. Here, the authors use mathematical modelling to investigate the potential disease, antimicrobial resistance, and economic implications of this intervention in gay, bisexual, and other men who have sex with men in Australia.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Bright electron bunches power particle physics and photon science. Here, reproducible bunches were generated in a plasma with simultaneous high charge per unit energy and low emittance, advancing a scheme to produce ultra-bright bunches in future.

Activators of K_Ca2.2 channels constitute potential novel treatments for neurologic disorders. Here, authors report cryo-EM structures of activator-bound channels, providing a framework for structure-based drug design targeting K_Ca2.2 channels.

NiPS₃ is a van der Waals antiferromagnetic semiconductor where the exciton formation is strongly influenced by the magnetic ordering. Previous studies have been limited to magneto-optical approaches, but here, Lebedev, Gish and coauthors succeed in making field effect transistors that operate below the Néel temperature and observe an ultranarrow electroluminescence with a high degree of linear polarization.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Self-assembled monolayers are efficient hole-selective contacts but suffer from aggregation and adhesion issues. To address these, Wang et al. introduce a dimeric molecular design that forms a hydrogen-bond network, enabling 28.4% certified efficiency in all-perovskite tandem solar cells.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

In a randomized study involving 9 general cardiologists and 107 real-world patient cases, assistance from a specifically tailored large language model resulted in preferable responses on complex case management compared to physicians alone, as rated by specialist cardiologists using a multidimensional scoring rubric.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

To humanize models of liver metabolic disease research, authors develop a microfluidic platform leveraging human hepatic spheroids integrated with microvasculature and circulating monocytes to model hepatic insulin resistance.

Transition of superfluid to insulator is observed in the layer-imbalanced regime of bilayer magnetoexcitons.

The study introduces radio interferometric multiplexed spectroscopy (RIMS), a method designed to efficiently monitor the radio emissions of massive samples of stars. Applying it to LOFAR data, the authors identify stellar bursts, offering clues to possible star–planet magnetic interactions.

Understanding the electric double layer of liquid–electrode interfaces is essential for understanding electrochemical processes. Now it has been shown that structure-dependent water dissociation and hydroxyl adsorption at step sites dictate the double-layer capacitance and potential of zero charge, directly linking model single crystals with practical platinum electrodes.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

In this study, Dahmane et al use a method called cryo-electron tomography to uncover new details of how tick-borne flaviviruses transform cells into virus factories.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

Based on two waves of data collection from 748 households in Hong Kong, this analysis sheds light on the number of transmission events that occurred before manifestation of symptoms in influenza A and B cases.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Cystine levels in pancreatic ductal adenocarcinoma (PDAC) tumour microenvironment are deficient, despite its crucial role for cancer cell maintenance. Here, the authors show that adaptation to cystine limitation stress promotes PDAC growth through induces metabolic reprogramming to promote PDAC tumor growth, while conferring a vulnerability in lipid metabolism targetable by lomitapide.

2D p-type transistors are essential for the realization of complementary circuits for post-silicon electronics. Here, the authors report a chloroform doping strategy to fabricate p-type monolayer WSe₂ transistors with high performance and long-term stability.

The inter-system crossing induced by selenium may undesirably enhance formation of triplet excitons in non-fullerene acceptors, leading to increased non-radiative losses. Here, the authors introduce achiral N-alkyl substituents, achieving maximum efficiency of 20.4% for ternary organic solar cells.

Here, the authors perform metagenomic analysis of Ecuadorian mothers and children showing that improved WASH and reduced animal exposure can lower antimicrobial resistance in the gut but may reduce gut microbial diversity, with the strongest effects observed in mothers.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

A suite of TadA-derived cytosine base editors was optimized to improve efficiency, reduce sequence bias, expand PAM compatibility and minimize artefacts, enabling precise genetic interrogation of variants of uncertain significance (VUS) in zebrafish.

Using eye-gaze methods, this research investigated infants’ ability to make moral character inferences. For a wide range of moral roles, infants could use an agent’s past moral behavior to revise their expectations for future moral behavior.

A combination of scanning probe microscopy and quantum sensing is used to investigate changes in water structure under confinement. A liquid–solid phase transition is observed in thin films of water below a confinement size of 2 nm at ambient temperature.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.