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Abstract Intraluminal epithelial abnormalities, potential precursors to significant conditions like cancer, necessitate early detection for improved prognosis. We present a motor-free telerobotic optical coherence tomography (OCT) endoscope that offers high-resolution intraluminal imaging and overcomes the limitations of traditional systems in navigating curved lumens. This system incorporates a compact magnetic rotor with a rotatable diametrically magnetized cylinder permanent magnet (RDPM) and a reflector, effectively mitigating thermal and electrical risks by utilizing an external magnetic field to maintain temperature increases below 0.5 °C and generated voltage under 0.02 mV. Additionally, a learning-based method corrects imaging distortions resulting from nonuniform rotational speeds. Demonstrating superior maneuverability, the device achieves steerable angles up to 110° and operates effectively in vivo, providing distortion-free 3D programmable imaging in mouse colons. This advancement represents a significant step towards guidewire-independent endomicroscopy, enhancing both safety and potential patient outcomes.

Abstract Electrokinetic force has been the major choice for driving the translocation of molecules through a nanopore. However, the use of this approach is limited by an uncontrollable translocation speed, resulting in non-uniform conductance signals with low conformational sensitivity, which hinders the accurate discrimination of the molecules. Here, we show the use of inertial-kinetic translocation induced by spinning an in-tube micro-pyramidal silicon nanopore fabricated using photovoltaic electrochemical etch-stop technique for biomolecular sensing. By adjusting the kinetic properties of a funnel-shaped centrifugal force field while maintaining a counter-balanced state of electrophoretic and electroosmotic effect in the nanopore, we achieved regulated translocation of proteins and obtained stable signals of long and adjustable dwell times and high conformational sensitivity. Moreover, we demonstrated instantaneous sensing and discrimination of molecular conformations and longitudinal monitoring of molecular reactions and conformation changes by wirelessly measuring characteristic features in current blockade readouts using the in-tube nanopore device.

It is often tempting for social media users to present themselves in an idealized way. Here, based on analyses of a large set of Facebook profiles together with a longitudinal experiment, the authors find evidence that more authentic self-expression may be psychologically beneficial, as it is related to greater well-being.

Sarcopenia is the loss of muscle mass and strength associated with physical disability during ageing. Here, the authors analyse muscle biopsies from 119 patients with sarcopenia and age-matched controls of different ethnic groups and find transcriptional signatures indicating mitochondrial dysfunction, associated with reduced mitochondria numbers and lower NAD+ levels in older individuals with sarcopenia.

Optical coherence tomography is an established optical tool for in vivo clinical imaging and diagnosis applications, but endoscopic technologies remain limited. Here, Yuan et al. develop a flexible, narrow diameter, super-achromatic endoscopic probe for ultrahigh-resolution in vivo OCT imaging of small luminal organs or narrow constrictions.

The original version of this Article contained an error in the third sentence of the ‘Animal studies’ section of the Methods, which incorrectly read ‘The sheep anesthesia was initiated with ketamine (25 mg kg−1) and then maintained by continuous intravascular (IV) infusion of propofol (800 mg kg−1 h−1) during imaging.’ The correct version states ‘800 µg kg−1 h−1’ in place of ‘800 mg kg−1 h−1’. This has been corrected in both the PDF and HTML versions of the article.

Tracking the time evolution of a quantum state allows one to verify the thermalization rate or the propagation speed of correlations in generic quantum systems. Inspired by the energy-time uncertainty principle, bounds have been demonstrated on the maximal speed at which a quantum state can change, resulting in immediate and practical tasks. Based on a programmable superconducting quantum processor, we test the dynamics of various emulated quantum mechanical systems encompassing single- and many-body states. We show that one can test the known quantum speed limits and that modifying a single Hamiltonian parameter allows the observation of the crossover of the different bounds on the dynamics. We also unveil the observation of minimal quantum speed limits in addition to more common maximal ones, i.e., the lowest rate of change of a unitarily evolved quantum state. Our results show a comprehensive experimental characterization of quantum speed limits and enhance the understanding for their subsequent study in engineered non-unitary conditions., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Carrier transport and recombination at the buried interface of perovskite have seriously restricted the further development of inverted perovskite solar cells (PSCs). Herein, an interfacial dipolar chemical bridge strategy to address this issue is presented. 2-(Diphenylphosphino) acetic acid (2DPAA) is selected as the linker to reconstruct the interfacial dipole, which effectively enlarges the interfacial dipole moment to 5.10 D and optimizes to a positive dipole orientation, thereby accelerating vertical hole transport, suppressing nonradiative recombination and promoting the perovskite crystallization. The champion inverted device yields a high power conversion efficiency (PCE) of 26.53% (certified 26.02%). Moreover, this strategy is extended to the wide-bandgap perovskite and large-area devices, which delivers high PCEs of 22.02% and 24.11%, respectively. The optimized devices without encapsulation also demonstrate great long-term shelf and operational stability. Our work highlights the importance of interfacial dipole moment and orientation at the buried interface to realize efficient and stable inverted PSCs., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Discharge of wastewater containing nitrate (NO 3 - ) disrupts aquatic ecosystems even at low concentrations. However, selective and rapid reduction of NO 3 - at low concentration to dinitrogen (N 2 ) is technically challenging. Here, we present an electrified membrane (EM) loaded with Sn pair-atom catalysts for highly efficient NO 3 - reduction to N 2 in a single-pass electrofiltration. The pair-atom design facilitates coupling of adsorbed N intermediates on adjacent Sn atoms to enhance N 2 selectivity, which is challenging with conventional fully-isolated single-atom catalyst design. The EM ensures sufficient exposure of the catalysts and intensifies the catalyst interaction with NO 3 - through mass transfer enhancement to provide more N intermediates for N 2 coupling. We further develop a reduced titanium dioxide EM as the anode to generate free chlorines for fully oxidizing the residual ammonia (<1 mg-N L -1 ) to N 2 . The sequential cathode-to-anode electrofiltration realizes near-complete removal of 10 mg-N L -1 NO 3 - and ~100% N 2 selectivity with a water resident time on the order of seconds. Our findings advance the single-atom catalyst design for NO 3 - reduction and provide a practical solution for NO 3 - contamination at low concentrations., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

In bioneuronal systems, the synergistic interaction between mechanosensitive piezo channels and neuronal synapses can convert and transmit pressure signals into complex temporal plastic pulses with excitatory and inhibitory features. However, existing artificial tactile neuromorphic systems struggle to replicate the elaborate temporal plasticity observed between excitatory and inhibitory features in biological systems, which is critical for the biomimetic processing and memorizing of tactile information. Here we demonstrate a mechano-gated iontronic piezomemristor with programmable temporal-tactile plasticity. This system utilizes a bicontinuous phase-transition heterogel as a stiffness-governed iontronic mechanogate to achieve bidirectional piezoresistive signals, resulting in wide-span dynamic tactile sensing. By micro-integrating the mechanogate with an oscillatory iontronic memristor, it exhibits stiffness-induced bipolarized excitatory and inhibitory neuromorphics, thereby enabling the activation of temporal-tactile memory and learning functions (e.g., Bienenstock-Cooper-Munro and Hebbian learning rules). Owing to dynamic covalent bond network and iontronic features, reconfigurable tactile plasticity can be achieved. Importantly, bridging to bioneuronal interfaces, these systems possess the capacity to construct a biohybrid perception-actuation circuit. We anticipate that such temporal plastic piezomemristor devices for abiotic-biotic interfaces can serve as promising hardware systems for interfacing dynamic tactile behaviors into diverse neuromodulations., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Compute-in-memory based on resistive random-access memory has emerged as a promising technology for accelerating neural networks on edge devices. It can reduce frequent data transfers and improve energy efficiency. However, the nonvolatile nature of resistive memory raises concerns that stored weights can be easily extracted during computation. To address this challenge, we propose RePACK, a threefold data protection scheme that safeguards neural network input, weight, and structural information. It utilizes a bipartite-sort coding scheme to store data with a fully on-chip physical unclonable function. Experimental results demonstrate the effectiveness of increasing enumeration complexity to 5.77 × 10 75 for a 128-column compute-in-memory core. We further implement and evaluate a RePACK computing system on a 40 nm resistive memory compute-in-memory chip. This work represents a step towards developing safe, robust, and efficient edge neural network accelerators. It potentially serves as the hardware infrastructure for edge devices in federated learning or other systems., Competing Interests: Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Solar-driven photocatalytic water splitting offers a sustainable pathway to produce green hydrogen, yet its practical application encounters several challenges including inefficient photocatalysts, sluggish water oxidation, severe reverse reactions and the necessity of separating produced hydrogen and oxygen gases. Herein, we design and develop a photocatalytic system composed of two separate reaction parts: a hydrogen evolution cell containing halide perovskite photocatalysts (MoSe 2 -loaded CH(NH 2 ) 2 PbBr 3-x I x ) and an oxygen evolution cell containing NiFe-layered double hydroxide modified BiVO 4 photocatalysts. These components are bridged by a I 3 - /I - redox couple to facilitate electron transfer, realizing efficient overall water splitting with a solar-to-hydrogen conversion efficiency of 2.47 ± 0.03%. Additionally, an outdoor scaled-up setup of 692.5 cm 2 achieves an average solar-to-hydrogen conversion efficiency of 1.21% during a week-long test under natural sunlight. By addressing major limitations inherent in conventional photocatalytic systems, such as the cooccurrence of hydrogen and oxygen in a single cell and the resultant severe reverse reactions from hydrogen and oxygen recombination, this work introduces an alternative concept for photocatalytic system design, which enhances both efficiency and practicality., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The chiral edge current is the boundary manifestation of the Chern number of a quantum anomalous Hall (QAH) insulator. The van der Waals antiferromagnet MnBi 2 Te 4 is theorized to be a QAH in odd-layers but has shown Hall resistivity below the quantization value at zero magnetic field. Here, we perform scanning superconducting quantum interference device (sSQUID) microscopy on these seemingly failed QAH insulators to image their current distribution. When gated to the charge neutral point, our device exhibits edge current, which flows unidirectionally on the odd-layer boundary both with vacuum and with the even-layers. The edge current chirality reverses with the magnetization of the bulk. Surprisingly, we find the edge channels coexist with finite bulk conduction even though the bulk chemical potential is in the band gap, suggesting their robustness under significant edge-bulk scattering. Our result establishes the existence of chiral edge currents in a topological antiferromagnet and offers an alternative for identifying QAH states., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Electrocatalytic gas-evolving reactions often result in bubble-covered surfaces, impeding the mass transfer to active sites. Such an issue will be worsened in practical high-current-density conditions and can cause sudden cell failure. Herein, we develop an on-chip microcell-based total-internal-reflection-fluorescence-microscopy to enable operando imaging of bubbles at sub-50 nm and dynamic probing of their nucleation during hydrogen evolution reaction. Using platinum-interfacial metal layer-graphene as model systems, we demonstrate that the strong binding energy between interfacial metal layer and graphene-evidenced by a reduced metal-support distance and enhanced charge transfer-facilitates hydrogen spillover from platinum to the graphene support due to lower energy barriers compared to the platinum-graphene system. This results in the spatial separation of bubble nucleation from the platinum surface, notably enhancing catalytic activity, as demonstrated in both microcell and polymer electrolyte membrane cell experiments. Our findings offer insights into bubble nucleation control and the design of electrocatalytic interfaces with minimized transfer resistance., Competing Interests: Competing interests: The Authors declare no competing interests., (© 2024. The Author(s).)

The multi-enzyme pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle and plays vital roles in metabolism, energy production, and cellular signaling. Although all components have been individually characterized, the intact PDHc structure remains unclear, hampering our understanding of its composition and dynamical catalytic mechanisms. Here, we report the in-situ architecture of intact mammalian PDHc by cryo-electron tomography. The organization of peripheral E1 and E3 components varies substantially among the observed PDHcs, with an average of 21 E1 surrounding each PDHc core, and up to 12 E3 locating primarily along the pentagonal openings. In addition, we observed dynamic interactions of the substrate translocating lipoyl domains (LDs) with both E1 and E2, and the interaction interfaces were further analyzed by molecular dynamics simulations. By revealing intrinsic dynamics of PDHc peripheral compositions, our findings indicate a distinctive activity regulation mechanism, through which the number of E1, E3 and functional LDs may be coordinated to meet constantly changing demands of metabolism., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Photocatalytic conversion has emerged as a promising strategy for harnessing renewable solar energy in the valorization of plastic waste. However, research on the photocatalytic transformation of plastics into valuable nitrogen-containing chemicals remains limited. In this study, we present a visible-light-driven pathway for the conversion of polylactic acid (PLA) into alanine under mild conditions. This process is catalyzed by defect-engineered CdS nanocrystals synthesized at room temperature. We observe a distinctive volcano-shaped relationship between sulfur vacancy content in CdS and the corresponding alanine production rate reaching up to 4.95 mmol/g catalyst/h at 70 o C. Ultraviolet-visible, photocurrent, electrochemical impedance, transient absorption, photoluminescence, and Fourier-transform infrared spectroscopy collectively highlight the crucial role of sulfur vacancies. The surface vacancies serve as adsorption sites for lactic acid; however, an excessive number of vacancies can hinder charge transfer efficiency. Sulfur vacancy-rich CdS exhibits high stability with maintained performance and morphology over several runs, effectively converts real-life PLA products and shows potential in the amination of other polyesters. This work not only highlights a facile approach for fabricating defect-engineered catalysts but also presents a sustainable method for upcycling plastic waste into valuable chemicals., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

In holometabolous insects, critical weight (CW) attainment triggers pupation and metamorphosis, but its mechanism remains unclear in non-model organisms like mosquitoes. Here, we investigate the role of 20-hydroxyecdysone (20E) in CW assessment and pupation timing in Aedes albopictus and Ae. aegypti, vectors of arboviruses including dengue and Zika. Our results show that the attainment of CW is contingent upon surpassing a critical 20E threshold, which results in entrance into a constant 22 h interval and the subsequent 20E pulse responsible for larval-pupal ecdysis. Sexual dimorphism in pupation time arises from higher basal 20E levels in males, enabling earlier CW attainment. Administering 20E at 50% of L3/L4 molt, when most of males but not females pass the pulse, results in female-specific lethality. These findings highlight the pivotal role of 20E thresholds in CW, pupation timing, and sexual dimorphism, suggesting that manipulating 20E levels can skew populations male, offering a potential mosquito sex separation strategy., Competing Interests: Competing interests: Z.X. is a co-founder and shareholder of Guangzhou Wolbaki Biotech Co., Ltd and a member of its scientific advisory board. The other authors declare no competing interests., (© 2025. The Author(s).)

Transcription elongation, especially RNA polymerase II (Pol II) pause-release, is less studied than transcription initiation in regulating gene expression during meiosis. It is also unclear how transcription elongation interplays with transcription initiation. Here, we show that depletion of NKAPL, a testis-specific protein distantly related to RNA splicing factors, causes male infertility in mice by blocking the meiotic exit and downregulating haploid genes. NKAPL binds to promoter-associated nascent transcripts and co-localizes with DNA-RNA hybrid R-loop structures at GAA-rich loci to enhance R-loop formation and facilitate Pol II pause-release. NKAPL depletion prolongs Pol II pauses and stalls the SOX30/HDAC3 transcription initiation complex on the chromatin. Genetic variants in NKAPL are associated with azoospermia in humans, while mice carrying an NKAPL frameshift mutation (M349fs) show defective meiotic exit and transcriptomic changes similar to NKAPL depletion. These findings identify NKAPL as an R-loop-recognizing factor that regulates transcription elongation, which coordinates the meiotic-to-postmeiotic transcriptome switch in alliance with the SOX30/HDAC3-mediated transcription initiation., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Biocrude derived from biomass via hydrothermal liquefaction (HTL) is a sustainable substitute for petroleum to obtain energy and biochemicals. Upgrading biocrude inevitably faces the trade-off between consuming large amounts of hydrogen via hydrotreating and high yield of solid residue without additional hydrogen. In this work, we report a non-hydrogenated refinery paradigm for nearly complete valorization (~90%), via co-generating green coal and bio-lubricant. The obtained green coal has higher heating values comparable to commercial coals, with a lower fuel ratio and reduced ash content. Viscosity of upgraded vacuum distillate is comparable to that of a lubricant oil. A life cycle assessment confirms 28% reduction in greenhouse gas emission and 35% reduction in energy input of this paradigm compared with conventional hydrotreating biorefinery. This approach presents an environmentally friendly, safe and convenient paradigm for biocrude refining from huge biowaste towards carbon-neutral society., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Chip scale DNA synthesis offers a high-throughput and cost-effective method for large-scale DNA-based information storage. Nevertheless, unbiased information retrieval from low-copy-number sequences remains a barricade that largely arises from the indispensable DNA amplification. Here, we devise a simulation-guided quantitative primer-template hybridization strategy to realize massively parallel homogeneous amplification of chip-scale DNA for DNA information storage (MPHAC-DIS). Using a fixed-energy primer design, we demonstrate the unbiasedness of MPHAC for amplifying 100,000-plex sequences. Simulations reveal that MPHAC achieves a fold-80 value of 1.0 compared to 3.2 with conventional fixed-length primers, lowering costs by up to four orders of magnitude through reduced over-sequencing. The MPHAC-DIS system using 35,406 encoded oligonucleotide allows simultaneous access of multimedia files including text, images, and videos with high decoding accuracy at very low sequencing depths. Specifically, even a ~ 1 ×  sequencing depth, with the combination of machine learning, results in an acceptable decoding accuracy of ~80%. The programmable and predictable MPHAC-DIS method thus opens new door for DNA-based large-scale data storage with potential industrial applications., Competing Interests: Competing interests: P.S. and Z.W. declare the patent CN116959573A, and C.F., P.S., and Z.W. declare the patent CN116417071A, both of which are related to the primer design methods used in this work. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Reactive oxygen species exacerbate nonalcoholic steatohepatitis (NASH) by oxidizing macromolecules; yet how they promote NASH remains poorly understood. Here, we show that peroxidase activity of global hepatic peroxiredoxin (PRDX) is significantly decreased in NASH, and palmitic acid (PA) binds to PRDX1 and inhibits its peroxidase activity. Using three genetic models, we demonstrate that hepatic PRDX1 protects against NASH in male mice. Mechanistically, PRDX1 suppresses STAT signaling and protects mitochondrial function by scavenging hydrogen peroxide, and mitigating the oxidation of protein tyrosine phosphatases and lipid peroxidation. We further identify rosmarinic acid (RA) as a potent agonist of PRDX1. As revealed by the complex crystal structure, RA binds to PRDX1 and stabilizes its peroxidatic cysteine. RA alleviates NASH through specifically activating PRDX1's peroxidase activity. Thus, beyond revealing the molecular mechanism underlying PA promoting oxidative stress and NASH, our study suggests that boosting PRDX1's peroxidase activity is a promising intervention for treating NASH., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

G protein-coupled receptor 4 (GPR4) belongs to the subfamily of proton-sensing GPCRs (psGPCRs), which detect pH changes in extracellular environment and regulate diverse physiological responses. GPR4 was found to be overactivated in acidic tumor microenvironment as well as inflammation sites, with a triad of acidic residues within the transmembrane domain identified as crucial for proton sensing. However, the 3D structure remains unknown, and the roles of other conserved residues within psGPCRs are not well understood. Here we report cryo-electron microscopy (cryo-EM) structures of active zebrafish GPR4 at both pH 6.5 and 8.5, each highlighting a distribution of histidine and acidic residues at the extracellular region. Cell-based assays show that these ionizable residues moderately influence the proton-sensing capacity of zebrafish GPR4, compared to the more significant effects of the triad residues. Furthermore, we reveal a cluster of aromatic residues within the orthosteric pocket that may propagate the signaling to the intercellular region via repacking the aromatic patch at the central region. This study provides a framework for future signaling and functional investigation of psGPCRs., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

As a medium to understand the nature of glass transition, ultrastable glasses have garnered increasing attention for their significance in fundamental science and technological applications. Most studies have produced ultrastable glasses through a surface-controlled process using physical vapor deposition. Here, we demonstrate an approach to accessing ultrastable glasses via the glass-to-glass transition, a bulk transformation that is inherently free from size constraints and anisotropy. The resulting ultrastable glass exhibits a significantly enhanced density (improved by 2.3%), along with high thermodynamic, kinetic, and mechanical stability. Furthermore, we propose that this method of accessing ultrastable glasses is general for metallic glasses, based on the examination of the competitive relationship between the glass-to-glass transition and crystallization. This strategy is expected to facilitate the proliferation of the ultrastable glass family, helping to resolve the instability issues of glass materials and devices and deepen our understanding of glasses and the glass transition., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive moderately K + -selective channelrhodopsin (HcKCR1-hs) by molecular engineering of the recently discovered Hyphochytrium catenoides kalium (potassium) channelrhodopsin 1. Transcranial activation of HcKCR1-hs significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several status epilepticus mouse models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings., Competing Interests: Competing interests: K.S., X.D. C.Z. and Y.W. have filed a patent application related to this work. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions. HSC-specific depletion of ATF4 suppresses liver fibrosis in vivo. Mechanistically, TGFβ resets ATF4 to orchestrate a unique enhancer program for the transcriptional activation of pro-fibrotic EMT genes. Analysis of human data confirms a strong correlation between HSC ATF4 expression and liver fibrosis progression. Importantly, a small molecule inhibitor targeting ATF4 translation effectively mitigates liver fibrosis. Together, our findings identify a mechanism promoting liver fibrosis and reveal new opportunities for treating this otherwise non-targetable disease., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

UHRF1 maintains DNA methylation by recruiting DNA methyltransferases to chromatin. In mouse, these dynamics are potently antagonized by a natural UHRF1 inhibitory protein STELLA, while the comparable effects of its human ortholog are insufficiently characterized, especially in cancer cells. Herein, we demonstrate that human STELLA (hSTELLA) is inadequate, while mouse STELLA (mSTELLA) is fully proficient in inhibiting the abnormal DNA methylation and oncogenic functions of UHRF1 in human cancer cells. Structural studies reveal a region of low sequence homology between these STELLA orthologs that allows mSTELLA but not hSTELLA to bind tightly and cooperatively to the essential histone-binding, linked tandem Tudor domain and plant homeodomain (TTD-PHD) of UHRF1, thus mediating ortholog-specific UHRF1 inhibition. For translating these findings to cancer therapy, we use a lipid nanoparticle (LNP)-mediated mRNA delivery approach in which the short mSTELLA, but not hSTELLA regions are required to reverse cancer-specific DNA hypermethylation and impair colorectal cancer tumorigenicity., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The role of dairy products in cardiovascular disease (CVD) prevention remains controversial. This study investigates the association between dairy consumption and CVD incidence using data from the China Kadoorie Biobank and the UK Biobank, complemented by an updated meta-analysis. Among Chinese participants, regular dairy consumption (primarily whole milk) is associated with a 9% increased risk of coronary heart disease (CHD) and a 6% reduced risk of stroke compared to non-consumers. Among British participants, total dairy consumption is linked to lower risks of CVD, CHD, and ischemic stroke, with cheese and semi-skimmed/skimmed milk contributing to reduced CVD risk. Meta-analysis reveals that total dairy consumption is associated with a 3.7% reduced risk of CVD and a 6% reduced risk of stroke. Notably, inverse associations with CVD incidence are observed for cheese and low-fat dairy products. Current evidence suggests that dairy consumption, particularly cheese, may have protective effects against CVD and stroke., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Dissection of the physiological interactomes of histone post-translational modifications (hPTMs) is crucial for understanding epigenetic regulatory pathways. Peptide- or protein-based histone photoaffinity tools expanded the ability to probe the epigenetic interactome, but in situ profiling in native cells remains challenging. Here, we develop a nucleus-targeting histone-tail-based photoaffinity probe capable of profiling the hPTM-mediated interactomes in native cells, by integrating cell-permeable and nuclear localization peptide modules into an hPTM peptide equipped with a photoreactive moiety. These types of probes, such as histone H3 lysine 4 trimethylation and histone H3 Lysine 9 crotonylation probes, enable the probing of epigenetic interactomes both in HeLa cell and hard-to-transfect RAW264.7 cells, resulting in the discovery of distinct interactors in different cell lines. The utility of this probe is further exemplified by characterizing interactome of emerging hPTM, such as AF9 was detected as a binder of histone H3 Lysine 9 lactylation, thus expanding the toolbox for profiling of hPTM-mediated PPIs in live cells., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The relative contributions of mutation rate variation, selection, and recombination in shaping genomic variation in bacterial populations remain poorly understood. Here we analyze 3318 Yersinia pestis genomes, spanning nearly a century and including 2336 newly sequenced strains, to shed light on the patterns of genetic diversity and variation distribution at the population level. We identify 45 genomic regions ("hot regions", HRs) that, although comprising a minor fraction of the genome, are hotbeds of genetic variation. These HRs are distributed non-randomly across Y. pestis phylogenetic lineages and are primarily linked to regulatory genes, underscoring their potential functional significance. We explore various factors contributing to the shaping and maintenance of HRs, including genomic context, homologous recombination, mutation rate variation and natural selection. Our findings suggest that positive selection is likely the primary driver behind the emergence of HRs, but not the sole force, as evidenced by the pronounced trend of variation purging within these regions., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Ferroelectric semiconductors have the advantages of switchable polarization ferroelectric field regulation and semiconductor transport characteristics, which are highly promising in ferroelectric transistors and nonvolatile memory. However, it is difficult to prepare a Sn-based perovskite film with both robust ferroelectric and semiconductor properties. Here, by doping with 2-methylbenzimidazole, Sn-based perovskite [93.3 mol% (FA 0.86 Cs 0.14 )SnI 3 and 6.7 mol% PEA 2 SnI 4 ] semiconductor films are transformed into ferroelectric semiconductor films, owing to molecular reconfiguration. The reconfigured ferroelectric semiconductors exhibit a high remanent polarization (P r ) of 23.2 μC/cm 2 . The emergence of ferroelectricity can be ascribed to the hydrogen bond enhancement after imidazole molecular doping, and then the spatial symmetry breaks causing the positive and negative charge centers to become non-coincident. Remarkably, the transistors based on perovskite ferroelectric semiconductors have a low subthreshold swing of 67 mv/dec, which further substantiates the superiority of introducing ferroelectricity. This work has developed a method to realize Sn-based ferroelectric semiconductor films for electronic device applications., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The composition in ferroelectric oxide films is decisive for optimizing properties and device performances. Controlling a composition distribution in these films by a facile approach is thus highly desired. In this work, we report a solution epitaxy of PbZr x Ti 1-x O 3 films with a continuous gradient of Zr concentration, realized by a competitive growth at ~220 °C. These intriguing films demonstrate a frequency-independent of dielectric permittivity below 100 kHz from room-temperature to 280 °C. In particular, the permittivity of the films can be largely regulated from 100 to 50 by slightly varying Zr compositional gradient. These results were revealed to arise from a built-in electric field within the films due to a coupling between the composition gradient and unidirectional spontaneous polarization. Our findings may pave a way to prepare compositionally-graded ferroelectric films by a solution approach, which is promising for practical dielectric, pyroelectric and photoelectric technical applications., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ideal root system architecture (RSA) is important for efficient nutrient uptake and high yield in crops. We cloned and characterized a key RSA regulatory gene, GRAVITROPISM LOSS 1 (OsGLS1), in rice (Oryza sativa L.). The gls1 mutant displays an increased root growth angle, longer primary roots, more adventitious roots and greater nutrient uptake efficiency and grain yield in paddy fields. OsGLS1 is strongly expressed in the root tips of seedlings and in leaves at the flowering stage. OsGLS1 encodes a RING finger E3 ubiquitin ligase mainly localizing at the basal plasma membrane (PM) in several root cell types when phosphorylated on its Ser-30 residue. OsGLS1 interacts with, ubiquitinates and promotes the degradation of basally localized PIN-FORMED 2 (OsPIN2) via the 26S proteasome, thus establishing the typical apical PM localization of OsPIN2 and polar auxin transport, ultimately shaping RSA. This previously unidentified OsGLS1-OsPIN2 regulatory pathway will contribute to an optimal RSA for enhancing nutrient efficiency in rice and other crops., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Few metrics exist to describe phenotypic diversity within ophthalmic imaging datasets, with researchers often using ethnicity as a surrogate marker for biological variability. We derived a continuous, measured metric, the retinal pigment score (RPS), that quantifies the degree of pigmentation from a colour fundus photograph of the eye. RPS was validated using two large epidemiological studies with demographic and genetic data (UK Biobank and EPIC-Norfolk Study) and reproduced in a Tanzanian, an Australian, and a Chinese dataset. A genome-wide association study (GWAS) of RPS from UK Biobank identified 20 loci with known associations with skin, iris and hair pigmentation, of which eight were replicated in the EPIC-Norfolk cohort. There was a strong association between RPS and ethnicity, however, there was substantial overlap between each ethnicity and the respective distributions of RPS scores. RPS decouples traditional demographic variables from clinical imaging characteristics. RPS may serve as a useful metric to quantify the diversity of the training, validation, and testing datasets used in the development of AI algorithms to ensure adequate inclusion and explainability of the model performance, critical in evaluating all currently deployed AI models. The code to derive RPS is publicly available at: https://github.com/uw-biomedical-ml/retinal-pigmentation-score ., Competing Interests: Competing interests: A.P.K. has acted as a paid consultant or lecturer to Abbvie, Aerie, Allergan, Google Health, Heidelberg Engineering, Novartis, Reichert, Santen,Thea and Topcon. A.Y.L. reports support from the US Food and Drug Administration, grants from Santen, Carl Zeiss Meditec, and Novartis, personal fees from Genentech, Topcon, and Verana Health, outside of the submitted work; This article does not reflect the opinions of the Food and Drug Administration. A.T. report grants from Bayer and Novartis and personal fees from Abbvie, Allegro, Annexon, Apellis, Bayer, Heidelberg Engineering, Iveric Bio, Kanghong, Novartis, Oxurion, Roche/Genentech, Thea. C.E. reports personal fees from Heidelberg Engineering, Boehringer Ingelheim, and Inozyme pharmaceuticals outside of the submitted work. P.A.K. has acted as a consultant for Retina Consultants of America, Topcon, Roche, Boehringer-Ingleheim, and Bitfount and is an equity owner in Big Picture Medical. He has received speaker fees from Zeiss, Novartis, Gyroscope, Boehringer-Ingleheim, Apellis, Roche, Abbvie, Topcon, and Hakim Group. He has received travel support from Bayer, Topcon, and Roche. He has attended advisory boards for Topcon, Bayer, Boehringer-Ingleheim, RetinAI, and Novartis. P.J.F. has acted as a consultant for Alphasights, GLG, Google Health, Guidepoint, PwC, Santen. A.B. is Founder and CEO of not-for-profit Peek Vision and receives a salary. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Chemiluminescence (CL) is a self-illuminating phenomenon fueled by chemical energy instead of extra excited light, which features superiority in sensitivity, signal-to-background ratios, and imaging depth. Strategies to synthesize a CL emission unimolecular skeleton in the second near-infrared window (NIR-II) and a unimolecular probe with direct duplex NIR-II [CL/fluorescence (FL)] emission are lacking. Here, we employ modular synthesis routes to construct a series of directly activated NIR-II CL emission unimolecular probes with a maximum emission wavelength of up to 1060 nm, and use them for real-time and continuous detection of the superoxide anion generated in acetaminophen induced liver injury in a female mice model under both NIR-II CL and NIR-II FL imaging channels. Thus, this study establishes a directly activatable NIR-II CL emission unimolecular skeleton, validating the scalability of this duplex NIR-II CL/FL imaging platform in bioactive molecule detection and disease diagnosis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Hardware implementation of reconfigurable and nonvolatile photoresponsivity is essential for advancing in-sensor computing for machine vision applications. However, existing reconfigurable photoresponsivity essentially depends on the photovoltaic effect of p-n junctions, which photoelectric efficiency is constrained by Shockley-Queisser limit and hinders the achievement of high-performance nonvolatile photoresponsivity. Here, we employ bulk photovoltaic effect of rhombohedral (3R) stacked/interlayer sliding tungsten disulfide (WS 2 ) to surpass this limit and realize highly reconfigurable, nonvolatile photoresponsivity with a retinomorphic photovoltaic device. The device is composed of graphene/3R-WS 2 /graphene all van der Waals layered structure, demonstrating a wide range of nonvolatile reconfigurable photoresponsivity from positive to negative ( ± 0.92 A W -1 ) modulated by the polarization of 3R-WS 2 . Further, we integrate this system with a convolutional neural network to achieve high-accuracy (100%) color image recognition at σ = 0.3 noise level within six epochs. Our findings highlight the transformative potential of bulk photovoltaic effect-based devices for efficient machine vision systems., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Optical aberrations hinder fluorescence microscopy of thick samples, reducing image signal, contrast, and resolution. Here we introduce a deep learning-based strategy for aberration compensation, improving image quality without slowing image acquisition, applying additional dose, or introducing more optics. Our method (i) introduces synthetic aberrations to images acquired on the shallow side of image stacks, making them resemble those acquired deeper into the volume and (ii) trains neural networks to reverse the effect of these aberrations. We use simulations and experiments to show that applying the trained 'de-aberration' networks outperforms alternative methods, providing restoration on par with adaptive optics techniques; and subsequently apply the networks to diverse datasets captured with confocal, light-sheet, multi-photon, and super-resolution microscopy. In all cases, the improved quality of the restored data facilitates qualitative image inspection and improves downstream image quantitation, including orientational analysis of blood vessels in mouse tissue and improved membrane and nuclear segmentation in C. elegans embryos., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Plant roots perceive heat stress (HS) and adapt their architecture accordingly, which in turn influence the yield in crops. Investigating their heterogeneity and cell type-specific response to HS is essential for improving crop resilience. Here, we generate single-cell transcriptional landscape of maize (Zea mays) roots in response to HS. We characterize 15 cell clusters corresponding to 9 major cell types and identify cortex as the main root cell type responsive to HS with the most differentially expressed genes and its trajectory being preferentially affected upon HS. We find that cortex size strongly correlated with heat tolerance that is experimentally validated by using inbred lines and genetic mutation analysis of one candidate gene in maize, providing potential HS tolerance indicator and targets for crop improvement. Moreover, interspecies comparison reveals conserved root cell types and core markers in response to HS in plants, which are experimentally validated. These results provide a universal atlas for unraveling the transcriptional programs that specify and maintain the cell identity of maize roots in response to HS at a cell type-specific level., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)