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This randomized open-label trial shows that hemoadsorption combined with hemodialysis reduces all-cause and cardiovascular mortality, and cardiovascular events in patients with end-stage kidney disease compared to hemodialysis (mainly low-flux hemodialysis plus intermittent hemodiafiltration) alone.

Personalized vaccines show some potential in leveraging tumor-specific adaptive immunity for cancer therapy. Here, this group reports an in-situ hydrogel vaccine serving as a sustained reservoir for a tumor-derived extracellular vesicle antigens for personalized cancer immunotherapy.

A hallmark of the interaction between flat band and dispersive band states in quantum materials is the flat band resonance. Here, the authors report the observation of a flat band resonance in the kagome bilayer material CsCr₆Sb₆ originating from the doublet kagome bands of the bilayer unit.

A “confined molecular encapsulation” strategy enables one-step fabrication of biomimetic ion-selective membranes. The in-situ formed MOFs with tunable sizes facilitate highly precise ion differentiation.

Systemic lupus erythematosus (SLE) is a complex autoimmune condition and treatment options have limited efficacy. Here, by analysis clinical samples and employing preclinical models, the authors show that cGAMP levels are elevated in the plasma of patients with SLE and that loss of cGAS ameliorates symptoms in an imiquimod-induced lupus model. Importantly, they identify prasugel as a cGAS inhibitor with promising therapeutic potential.

This study from Wei-Guang Li, Tian-Le Xu and colleagues shows that neuropeptide Y released by specific hippocampal inhibitory neurons can switch fear memories into extinction memories by acting on two distinct receptor-defined neuron populations.

Here, the authors demonstrate that Inhibiting PTBP1 corrects E2A splicing imbalance, reprograms muscle cell development, and rescues defective muscle regeneration in a Duchenne muscular dystrophy mouse model.

In this work, authors develop and validate a plasma proteomics-based model for the prediction of secondary infections in hepatitis B virus-related liver failure.

Both endogenous and exogenous signaling pathways are involved in the maintenance of self-renewal and pluripotency of human embryonic stem cells (hESCs). Here, the authors uncover that endogenous VEGF signaling safeguards pluripotency and prevents extra-embryonic differentiation in primed hESCs via activation of transcription factor NANOG and suppression of BMP signaling activity.

The α-C–C cleavage of ketones provides a versatile route for C–C bond formation but remains challenging, particularly for selective cross-coupling between distinct ketones. Here the authors report a nickel- and photocatalysis-enabled deacylative coupling via bimolecular homolytic substitution to forge diverse C(sp³)–C(sp³) bonds.

Zhang et al. show that the activation of RIPK1 is suppressed by acetylhypusination in a spermidine-dependent manner. Disruption of this axis contributes to RIPK1-mediated vascular pathology to promote insulin resistance and diabetic kidney pathology.

Zinc isotopes in basalts along a 1,100-km transect of the Gakkel Ridge record widespread mantle recycling of surface carbonates via ancient oceanic subduction, explaining the unusually carbon-rich nature of the Arctic asthenosphere.

Tumors remain difficult to map. Here, the authors developed a 2.5 mm magnetic-driven multifunctional optoelectronic catheter that enables minimally invasive tumor mapping, targeted drug delivery, in situ sensing, and photodynamic therapy.

This study looks at Jiang Han Road in Wuhan, one of the most influential shopping streets in the city center, and examines the impacts of digitalization in the post-COVID era. It found a shift in the economic activity towards socialization in the digital space, and revealed key socioeconomic-spatial patterns fostering the adaptive capacity of the street.

NPM3 promotes histone lactylation (H3K18la/K27la) and drives FASN transcription and cardiomyocyte necroptosis in diabetic cardiomyopathy. Targeting this pathway with dihydroartemisinin alleviates cardiac dysfunction.

Aging is companied by a progressive decline of physiological functions. Here, the authors report that dihydromyricetin, a plant derived dietary supplement, generates senotherapeutic effects and shows great promise to ameliorate age-related conditions via pharmaceutical intervention.

This study reveals three distinct brain patterns in insufficient sleep adolescents, each linked to unique factors of genetics, environmental disturbances, or psychiatric risk.

In a phase 1 trial enrolling six patients with heterozygous familial hypercholesterolemia, treatment with lipid nanoparticles designed for base editing and inactivation of PCSK9 in hepatocytes showed preliminary evidence of reduced low-density lipoprotein levels without the occurrence of serious adverse events or evidence of off-target editing.

The interaction between immune cells and the peripheral nervous system during the progression of vascular diseases is poorly understood. Here, the authors use a mouse model of neointimal hyperplasia (NIH) and show that Tenascin (Tnc)-positive myofibroblasts originate from adventitial fibroblasts and promote activation of sensory nerves and CCL-2-dependent accumulation of macrophages to drive inflammation and vascular remodeling.

This work effectively addresses the long-standing challenge of competitive kinetics in heterogeneous Fenton-like systems through the synergistic interaction between nitrogen vacancies (Nv) and Fe sites on carbon nitride.

Myocardial ischemia-reperfusion injury is driven by interconnected pyroptosis, apoptosis, and necroptosis, making single-pathway inhibition ineffective. The authors show Prussian blue nanoparticles block multiple PANoptosomes and restore mitochondrial and immune homeostasis, markedly reducing PANoptosis and improving cardiac repair.

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.

The ring-opening functionalization of strained rings represents a highly valuable transformation, but existing strategies predominantly focus on ring-opening difunctionalization. Now a multisite, programmable, divergent ring-opening functionalization of strained rings via the electro-oxidation of continuous C–C bond and multiple C(sp³)–H bonds has been developed.

Metabolic reprogramming of immune cells can modulate their response to and ability to respond in infective contexts. Here the authors show phosphoglycerate dehydrogenase mediated serine reprogramming in macrophage is linked to hyper inflammatory responses in murine models of Pseudomonas aeruginosa pneumonia.

Traditional iterative catalysis in RiPP biosynthesis typically modifies linear peptides. Here the authors discover GNAT enzymes that iteratively modify fully folded lasso peptides and engineer them to create lipolasso peptides with expanded chemical diversity.

The authors use Perturb-seq analysis in human pancreatic islet beta cells, as well as in vivo and in vitro analyses, to identify potential therapeutic targets for type 2 diabetes, including ZZEF1, which regulates insulin synthesis and cellular stress in islet β cells.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

A quasi-melting transfer technique enables clean, sequential transfer of graphene and hexagonal boron nitride monolayers from germanium substrates under vacuum conditions. Controlled lattice alignment yields atomically precise, wrinkle-free superlattices with tunable stacking and twist angles, enabling scalable fabrication of high-quality 2D heterostructures for advanced electronics.

Farnesyl pyrophosphate—a mevalonate pathway metabolic intermediate—is an endogenous alarmin that enhances IgG antibody responses through keratinocyte-derived IL-6 and CCL20.

Hepatocyte-specific GPR110 mediates metabolic dysfunction-associated steatohepatitis progression by regulating hepatic oestrogen sensitivity in a sex-specific manner, specifically in female mice.

Brainstem gliomas are an aggressive form of paediatric cancer. Here, the authors use metabolomics to assess differences in metabolites during radiotherapy.

PARP inhibitors are effective in cancer patients with BRCA1 mutations but whether this can extend to BRCA1 wildtype patients by targeting BRCA1 transcriptional regulation is unclear. Here, in preclinical models of pancreatic cancer, the authors identify OFD1 as a transcriptional regulator of BRCA1 via the DREAM complex and as a potential therapeutic target in combination with PARP inhibition.

Screening spontaneous mutants reveals AMP EWAMP-R targets ClpX in E. coli, inhibits its ATPase activity, disrupts the SOS response, and induces apoptosis-like cell death. By contrast, in S. aureus, resistance only involves metabolic slowdown.

Generation of mature oocytes requires tight regulation of a discontinuous meiotic cell cycle. Here they show that the acetyltransferase Nat10 mediates modification of RNAs targeted for degradation and find that this process is essential for female oocyte meiosis and maturation.

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.

FGF13 is a member of the fibroblast growth factor family and lacks a signal peptide. Here, the authors show that FGF13 is downregulated in sepsis and show in mouse models that this protein accelerates septic lung injury and promotes TAK1/MEK/ERK signalling leading to HIF1a-regulated aerobic glycolysis in the inflammatory state.

Staphylococcus aureus can aggregate within human synovial fluid and lead to joint infections. Here, the authors reveal that the fatty acid kinase system and its downstream saeRS regulator control S. aureus aggregation within synovial fluid.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.