Browse Articles

Single-phage profiling illuminates viral individuality during bacterial cell fate determination

Long-term hyperglycaemia induces qualitative and quantitative changes in rat ultrasonic vocalizations

Integration of donor microbiota following FMT correlates with anti-PD-1 response in melanoma

Development of a biomarker-enhanced arterial age model for young-to-middle-aged adults with type 2 diabetes

Mitochondrial RNA degradation regulates differentiation, stemness, and immune sensitivity in acute myeloid leukemia

An accurate, efficient, and accessible AI-powered solution for wildlife re-identification in conservation

CryoWriter: a robotic solution for improved Cryo-EM grid preparation

Abstract Cryo-electron microscopy (cryo-EM) structure determination relies on preparing thin, vitreous films of sample solution on EM grids. Cryo-EM is a mature technology, but preparing the grids remains a major bottleneck. Here, we evaluate the cryoWriter, a blotting-free, microfluidic grid-preparation robot that writes nanoliter volumes onto EM grids in a controlled environment. Using capillary-writing in spiral or line patterns, we prepared high-quality grids from minimal sample volumes and obtained near-atomic reconstructions for test specimens, including TMV, apoferritin, and the membrane protein TRPM4. We further demonstrate programmable deposition modes, such as writing the sample twice to boost particle density, or two-line writing for on-grid mixing to visualize time-resolved protein–ligand binding. In a challenging case (NrS-1 DNA polymerase), the cryoWriter grids exhibited reduced orientation bias relative to conventional blotting, enabling a more isotropic reconstruction. These results show that the cryoWriter provides a versatile platform for reproducible low volume cryo-EM grid preparation and for on-grid biochemical workflows.

Dynamic system reliability under external shocks and internal markovian degradation

Abstract Systems operating in harsh environments face the dual challenge of external extreme shocks and internal degradation, a critical failure mode often overlooked in reliability engineering. This paper develops a novel $$\:{L}_{z}$$ -transform model to analyze this coupled effect dynamically. Applied to a Doubly-Fed Induction Generator (DFIG), the model reveals a severe decline in performance: availability and reliability deteriorate asymptotically toward zero due to these combined stressors, with reliability falling more sharply due to the irreversibility of failures. To address this, a new maintenance strategy using dummy states is proposed. This approach dramatically improves system resilience, elevating both reliability and availability to near-perfect levels (~ 1.0). Comparative analysis shows the strategy completely mitigates time-dependent degradation, sustaining high performance indefinitely and improving vulnerable systems by orders of magnitude. Crucially, benefits are solely due to maintenance, not redundancy. This study proves proactive maintenance is indispensable for sustainable operation in shock-prone environments.

Supercurrent effect in a charge density wave intertwined superconductor

Physical function impacts hearing without mediation from systolic blood pressure

AMOC slowdown amplifies North Atlantic salinity variability to unprecedented levels

Piezomagnetoelectric effects in a candidate Kitaev magnet

Abstract The exactly solvable Kitaev model with its frustrated bond-dependent interactions has attracted enormous attention due to its exotic physics hosting fractional spin excitations as well as its promising prospects for quantum information technology. However, there is no pristine realization of the Kitaev model due to the significant Heisenberg and off-diagonal exchange interactions. While these additional exchange interactions are considered as obstacles on the route towards the desired Kitaev quantum spin liquids, the interplay between these magnetic anisotropies and the Kitaev interaction has lead to numerous intriguing phenomena. Here we demonstrate a new phenomenon, the coexistence of the Kitaev interaction with the piezomagnetoelectric effect (simultaneous magnetoelastic and magnetoelectric responses), which can offer electric field driven manipulation of the ground state and the fractional spin excitations. Our study reports the direct observation of the magnetoelectric (ME) effect in a Kitaev-Heisenberg, the quantum spin liquid candidate Na 2 Co 2 TeO 6 , and highlights the magnetoelastic response as a sensitive gauge of phase transitions. We discuss that the ME effect originates from the p d -hybridization mechanism, which allows local polarization independently from any magnetic order. This mechanism can transfer the frustrated magnetic interactions onto the polarization system, potentially creating a new exotic electronic state, a polarization liquid.

Two Plasmodium vivax hypnozoite-expressed RNA-binding proteins inhibit liver stage replication

Abstract Plasmodium vivax (Pv) forms non-replicating liver stages called hypnozoites, which activate after primary infection, and cause relapses of symptomatic blood-stage malaria. We hypothesize that hypnozoites must actively suppress schizogony to maintain a quiescent state. Differential transcriptome prospecting identifies two hypnozoite-expressed transcripts encoding putative RNA-binding proteins. We assess the functional role of the two encoded proteins in Plasmodium yoelii (Py) , a rodent malaria parasite that naturally does not form hypnozoites. Strikingly, individual expression of each protein in Py liver stages blocks liver stage schizogony, with parasites remaining small and uninucleate. A screen of RNA sequences that interact with the putative RNA-binding domains of these proteins shows enrichment of distinct, highly specific motifs, indicating that they might block schizogony by binding RNAs containing these motifs. Our findings provide the unprecedented functional evidence for one potential molecular mechanism of hypnozoite formation. Based on their function we name these proteins IESI-1 and IESI-2 (Initiation of Exo-erythrocytic Schizogony Inhibited).

Electrostatic bimodality of human cytosolic DNA sensor cGAS-dsDNA condensates revealed by millisecond flashing electrophoretic separation

OFC-induced network modularity improves positive symptoms and attentional alertness in schizophrenia: a combined rTMS-fMRI study

Abstract Repetitive Transcranial Magnetic Stimulation (rTMS) targeting the orbitofrontal cortex (OFC) has emerged as a promisingerapeutic option for drug-naïve people with schizophrenia (SCZ). However, the putative underlying mechanisms of OFC-induced physiological effects remain unknown. In this completed randomized, double-blind, placebo-controlled trial (ChiCTR2000041106), we delivered 4 weeks of low-frequency rTMS to the right OFC in SCZ, with participants receiving either active or sham stimulation, and followed a network neuroscience framework to explore the alteration of dynamic modularity induced by the OFC. The trial met its pre-specificized primary endpoint following active treatment. Neuroimaging analysis reported here were secondary outcomes. We found that the modularization between OFC and the default mode network (DMN) across time windows supported improvements in symptoms and cognitive function. This dynamics pattern was spatially constrained, with stronger rTMS modulation observed in DMN regions centered on the ventromedial prefrontal cortex (vmPFC). The spatial topography of this pattern was correlated with the expression of schizophrenia-related genes and markers of excitatory neurotransmission, supporting its biological relevance. Crucially, such cascade of physiological effects was specifically linked to improvements in cognitive attention/vigilance and were modulated by their positive symptoms. Exploratory analyses showed that OFC-induced modularity weakened the DMN’s causality over the downstream attention network. These findings reveal the important role for the dynamic modularity of the OFC as an “intermediate phenotype” mediating the pathway from genetic variation to behavioral manifestations, highlighting the potential of low-frequency stimulation of the OFC as a therapeutic strategy for specific subgroups of SCZ, especially those with positive symptoms and attention deficits.

Measurement of analogue Hawking radiation stimulated by a single photon

Children use algorithm induction to discover patterns in data

Abstract Humans are unique in our ability to acquire diverse skills and inhabit myriad environments, but the cognitive mechanisms underlying such fast, flexible learning remain unresolved. Inspired by theories of artificial intelligence, here we show evidence for one such learning mechanism - program induction - in US American and indigenous Tsimane’ children in the Bolivian Amazon. Participants viewed novel patterns and were asked to generalize them to new stimuli, alphabets, and lengths, without feedback. Given very limited data, participants across ages, cultures, and conditions constructed response patterns that shared abstract structure with the sample patterns. Computational modeling shows that responses likely reflect discovery of latent rules, rather than simple heuristics or associations, even among children without formal schooling. The results suggest program induction serves as a domain-general learning mechanism from early in life, allowing children across cultures to rapidly infer the algorithmic structure of their natural and cultural environment, whatever it might be.

Pan-cancer single-cell atlases of mouse and human tumor-associated dendritic cells

COXFA4L2 upregulation preserves residual cytochrome c oxidase activity in COXFA4-related Leigh-like encephalopathy

Abstract Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a well-established cause of PMD, leading to a broad spectrum of phenotypes. COXFA4 (cytochrome c oxidase subunit FA4), formerly NDUFA4, is a nuclear-encoded COX subunit, but its role in disease remains poorly defined. We report the largest genetically confirmed cohort of COXFA4-related PMD to date, comprising 13 individuals from 12 families with biallelic pathogenic COXFA4 variants. All present with Leigh-like encephalopathy and complete loss of COXFA4 protein; however, patient-derived fibroblasts retain residual COX activity, with upregulation of COXFA4L2 (cytochrome c oxidase subunit FA4-like 2), a poorly characterised paralog. Here, we show that COXFA4 is a late-stage COX assembly subunit and identify a paralog-mediated compensatory mechanism with translational potential.

High-throughput production of microbatteries by a stack-punching method