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Antibodies are essential biological research tools and important therapeutic agents, but some exhibit non-specific binding to off-target proteins and other biomolecules. Such polyreactive antibodies compromise screening pipelines, lead to incorrect and irreproducible experimental results, and are generally intractable for clinical development. Here, we design a set of experiments using a diverse naïve synthetic camelid antibody fragment (nanobody) library to enable machine learning models to accurately assess polyreactivity from protein sequence (AUC > 0.8). Moreover, our models provide quantitative scoring metrics that predict the effect of amino acid substitutions on polyreactivity. We experimentally test our models' performance on three independent nanobody scaffolds, where over 90% of predicted substitutions successfully reduced polyreactivity. Importantly, the models allow us to diminish the polyreactivity of an angiotensin II type I receptor antagonist nanobody, without compromising its functional properties. We provide a companion web-server that offers a straightforward means of predicting polyreactivity and polyreactivity-reducing mutations for any given nanobody sequence.

Enzyme orthologs sharing identical primary functions can have different promiscuous activities. While it is possible to mine this natural diversity to obtain useful biocatalysts, generating comparably rich ortholog diversity is difficult, as it is the product of deep evolutionary processes occurring in a multitude of separate species and populations. Here, we take a first step in recapitulating the depth and scale of natural ortholog evolution on laboratory timescales. Using a continuous directed evolution platform called OrthoRep, we rapidly evolve the Thermotoga maritima tryptophan synthase β-subunit (TmTrpB) through multi-mutation pathways in many independent replicates, selecting only on TmTrpB's primary activity of synthesizing L-tryptophan from indole and L-serine. We find that the resulting sequence-diverse TmTrpB variants span a range of substrate profiles useful in industrial biocatalysis and suggest that the depth and scale of evolution that OrthoRep affords will be generally valuable in enzyme engineering and the evolution of biomolecular functions.

Off-target binding hinders the development of therapeutic antibodies and reproducibility in basic research settings. Here the authors develop a method to quantify and reduce the polyreactivity of antibody fragments based on protein sequence alone.

The material class of rare earth nickelates with high Ni3+ oxidation state is generating continued interest due to the occurrence of a metal-insulator transition with charge order and the appearance of non-collinear magnetic phases within this insulating regime. The recent theoretical prediction for superconductivity in LaNiO3thin films has also triggered intensive research efforts. LaNiO3 seems to be the only rare earth nickelate that stays metallic and paramagnetic down to lowest temperatures. So far, centimeter-sized impurity-free single crystal growth has not been reported for the rare earth nickelates material class since elevated oxygen pressures are required for their synthesis. Here, we report on the successful growth of centimeter-sized LaNiO3 single crystals by the floating zone technique at oxygen pressures of up to 150 bar. Our crystals are essentially free from Ni2+ impurities and exhibit metallic properties together with an unexpected but clear antiferromagnetic transition. [ABSTRACT FROM AUTHOR]

As a well-known cancer risk region, the 8q24 locus is frequently amplified in a variety of solid tumors. Here we identify a pseudogene-derived oncogenic lncRNA, ZNF252P, which is upregulated in a variety of cancer types by copy number gain as well as c-Myc-mediated transcriptional activation. Mechanistically, ZNF252P binds and drives "phase separation" of HNRNPK and ILF3 protein in the nucleus and cytoplasm, respectively, to transcriptionally and posttranscriptionally activate c-Myc, thus forming a c-Myc/ZNF252P/c-Myc positive feedback loop. These findings expand the understanding of the relationship between genomic instability in the 8q24 region and tumorigenesis and clarify a regulatory mechanism involved in transcription and posttranscription from the perspective of RNA-mediated nuclear and cytoplasmic protein phase separation, which sheds light on the dialogue with the driver oncogene c-Myc. The pivotal regulatory axis of ZNF252P/c-Myc has potential as a promising biomarker and therapeutic target in cancer development., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Nutrient competition with indigenous microbes or pathogens presents a significant challenge for oral probiotic efficacy. To address this issue, we develop an ameba-inspired food-carrying strategy (AIFS) by prebinding ginger-derived exosome-like nanoparticles (GELNs) onto probiotics as food depots. AIFS enables probiotics to efficiently and exclusively consume GELNs in situ, even in the presence of competing bacteria. This results in up to 21 times higher uptake efficiency compared to unengineered probiotics, dramatically accelerating probiotic proliferation. Meanwhile, AIFS potentiates probiotics' resistance to multiple GI stressors. In a murine model of colitis, AIFS can improve the abundance of probiotics and inhibit pathogens, maintaining intestinal flora homeostasis. Additionally, it can upregulate the anti-inflammatory IL-10, reduce the proinflammatory IL-1β, and repair damaged intestinal mucus. Thereby, AIFS displays potently elevated prophylactic and therapeutic efficacy for colitis mice. This work provides a method for microbial engineering, with broad implications for microbiotherapy and gut health., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

SnSe crystal has witnessed significant advancements as a promising thermoelectric material over the past decade. Its in-plane direction shows robust mechanical strength for practical thermoelectric applications. Herein, we optimize the in-plane thermoelectric performance of n-type SnSe by crystal symmetry modification. In particular, we find that Te and Mo alloying continuously enhances the crystal symmetry, thereby increasing the carrier mobility to ~ 422 cm 2  V -1 s -1 . Simultaneously, the conduction bands converge with the symmetry modification, further improving the electrical transport. Additionally, the lattice thermal conductivity is limited to ~ 1.1 W m -1 K -1 due to the softness of both acoustic and optical branches. Consequently, we achieve a power factor of ~ 28 μW cm -1 K -2 and ZT of ~ 0.6 in n-type SnSe at 300 K. The average ZT reaches ~ 0.89 at 300-723 K. The single-leg device based on the obtained n-type SnSe shows a remarkable efficiency of ~ 5.3% under the ΔT of ~ 300 K, which is the highest reported in n-type SnSe. This work demonstrates the substantial potential of SnSe for practical applications of power generation and waste heat recovery., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The quantum anomalous Hall effect in layered antiferromagnet MnBi 2 Te 4 harbors a rich interplay between magnetism and topology, holding a significant promise for low-power electronic devices and topological antiferromagnetic spintronics. In recent years, MnBi 2 Te 4 has garnered considerable attention as the only known material to exhibit the antiferromagnetic quantum anomalous Hall effect. However, this field faces significant challenges as the quantization at zero magnetic field depending critically on fabricating high-quality devices. In this article, we introduce a straightforward yet effective method to mitigate the detrimental effect of the standard fabrication on MnBi 2 Te 4 by depositing an AlO x layer on the surface before fabrication. Optical contrast and magnetotransport measurements on over 50 MnBi 2 Te 4 demonstrate that AlO x can effectively preserve the pristine states of the devices. Surprisingly, we find this simple method can significantly enhance the anomalous Hall effect towards quantization, which resolves a longstanding challenge in the field of MnBi 2 Te 4 . Scaling relation analysis further reveals the intrinsic mechanism of anomalous Hall effect dominated by Berry curvature at various magnetic configuration. By tuning the gate voltage, we uncover a gate independent magnetism in odd-layer MnBi 2 Te 4 devices. Our experiments not only pave the way for the fabrication of high-quality dissipationless transport devices, but also advance the investigation of exotic topological quantum phenomena in 2D materials., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Obesity is regarded as a chronic inflammatory disease involving adipose tissue macrophages (ATM), but whether immunometabolic reprogramming of ATM affects obesity remains unclarified. Here we show that in ATM glutaminolysis is the fundamental metabolic flux providing energy and substrate, bridging with AMP-activated protein kinase (AMPK) activity, succinate-induced interleukin-1β (IL-1β) production, and obesity. Abrogation of AMPKα in myeloid cells promotes proinflammatory ATM, impairs thermogenesis and energy expenditure, and aggravates obesity in mice fed with high-fat diet (HFD). Conversely, IL-1β neutralization or myeloid IL-1β abrogation prevents obesity caused by AMPKα deficiency. Mechanistically, ATP generated from glutaminolysis suppresses AMPK to decrease phosphorylation of the β subunit of succinyl-CoA synthetase (SUCLA2), thereby resulting in the activation of succinyl-CoA synthetase and the overproduction of succinate and IL-1β; by contrast, siRNA-mediated SUCLA2 knockdown reduces obesity induced by HFD in mice. Lastly, phosphorylated SUCLA2 in ATM correlates negatively with obesity in humans. Our results thus implicate a glutaminolysis/AMPK/SUCLA2/IL-1β axis of inflammation and obesity regulation in ATM., Competing Interests: Competing interests: The authors declare no competing interest., (© 2025. The Author(s).)

High-performance superelastic materials with a combination of high superelastic stress, large elastic recovery strain, and stable elastic modulus over a wide temperature range are highly desired for a variety of technological applications. Unfortunately, it is difficult to achieve these multi-functionalities simultaneously because most superelastic materials have to encounter the modulus softening effect and the limited superelastic stress, whereas most Elinvar-type materials show small elastic strain limit. Here, we report a (TiZrHf) 44 Ni 25 Cu 15 Co 10 Nb 6 high-entropy alloy that meets all these requirements. This alloy also shows good cyclic stability, thermally-stable capacity for elastic energy storage, high micro-hardness and good corrosion resistance, allowing it to operate stably in hostile environments. We show that its multi-functionalities stem from a natural composite microstructure, containing a highly-distorted matrix phase with strain glass transition and various structural and compositional heterogeneities from micro- to nano-scale. Our findings may provide insight into designing high-entropy alloys with unconventional and technologically-important functional properties., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Accurate, practical, and robust evaluation of the battery state of health is crucial to the efficient and reliable operation of electric vehicles. However, the limited availability of large-scale, high-quality field data hinders the development of the battery management system for state of health estimation, lifetime prediction, and fault detection in various applications. In this work, to gain insights into underlying factors limiting battery management system performance in real-world vehicles, we analyze the operational data of 300 diverse electric vehicles over three years to understand the disparities between field data and laboratory battery test data and their effect on state of health estimation. Furthermore, we propose a deep learning-based multi-modal framework to effectively leverage historical vehicle data for efficient, accurate, and cost-effective state of health estimation. The proposed paradigm exhibits considerable potential for numerous applications in state estimation and diagnostics in multi-sensor systems. Furthermore, we make the field data of these electric vehicles publicly available aiming to promote further research on the development of effective and reliable battery management systems for real-world vehicles., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The unsatisfactory ionic conductivity of solid polymer electrolytes hinders their practical use as substitutes for liquid electrolytes to address safety concerns. Although various plasticizers have been introduced to improve lithium-ion conduction kinetics, the lack of microenvironment understanding impedes the rational design of high-performance polymer electrolytes. Here, we design a class of Hofmann complexes that offer continuous two-dimensional lithium-ion conduction channels with functional ligands, creating highly conductive electrolytes. Assisting with unsupervised learning, we use Climbing Image-Nudged Elastic Band simulations to screen lithium-ion conductors and screen out five potential candidates that elucidate the impact of lithium coordination environment on conduction behavior. By adjusting the covalency competition between Metal-O and Li-O bonds within Hofmann complexes, we can manipulate weak coordination environment of lithium-ion for rapid conduction kinetics. Li | |sulfurized polyacrylonitrile (SPAN) cell using solid-state polymer electrolytes with predicted Co(dimethylformamide) 2 Ni(CN) 4 delivers an initial discharge capacity of 1264 mAh g -1 with a capacity retention of 65% after 500 cycles at 0.2 C (335 mA g -1 ), at 30 °C ± 3 °C. The assembled 0.6 Ah Li | |SPAN pouch cell delivers an areal discharge capacity of 3.8 mAh cm -2 at the second cycle with a solid electrolyte areal mass loading of 18.6 mg cm -2 (mass-to-capacity ratio of 4.9)., 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).)

The interfacial molecular dipole enhances the photovoltaic performance of perovskite solar cells (PSCs) by facilitating improved charge extraction. However, conventional self-assembled monolayers (SAMs) face challenges like inadequate interface coverage and weak dipole interactions. Herein, we develop a strategy using a self-assembled ferroelectric layer to modify the interfacial properties of PSCs. Specifically, we employ 1-adamantanamine hydroiodide (ADAI) to establish robust chemical interactions and create a dipole layer over the perovskite. The oriented molecular packing and spontaneous polarity of ferroelectric ADAI generate a substantial interfacial dipole, adjusting band bending at the anode, reducing band misalignment, and suppressing charge recombination. Consequently, our formamidinium lead iodide-based conventional PSC achieves efficiencies of 25.13% (0.06 cm 2 ) and 23.5% (1.00 cm 2 ) while exhibiting enhanced stability. Notably, we demonstrate an impressive efficiency of 25.59% (certified at 25.36%) in a 0.06 cm 2 area for the inverted champion device, showcasing the promise of ferroelectric SAMs for PSCs performance enhancement., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Electric field induced antiferroelectric-ferroelectric phase transition is a double-edged sword for energy storage properties, which not only offers a congenital superiority with substantial energy storage density but also poses significant challenges such as large polarization hysteresis and poor efficiency, deteriorating the operation and service life of capacitors. Here, entropy increase effect is utilized to simultaneously break the long-range antiferroelectric order and locally adjust the fourfold commensurate modulated polarization configuration, leading to a breakthrough in the trade-off between recoverable energy storge density (14.8 J cm -3 ) and efficiency (90.2%) in medium-entropy antiferroelectrics. The embedding of non-polar phase regions in the incommensurate antiferroelectric matrices, revealing as a mixture of commensurate, incommensurate, and relaxor antiferroelectric polarization configurations, contributes to the diffuse antiferroelectric-ferroelectric phase transition, enhanced phase transition electric field, delayed polarization saturation, and efficient recovery of polarization. This work demonstrates that controlling local diverse antiferroelectric polarization configurations by increasing entropy is an effective avenue to develop high-performance energy storage antiferroelectrics, with implications that can be extended to other materials and functionalities., Competing Interests: Competing interests: The 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).)

The anomalous photovoltaic effect (APE) in polar crystals is a promising avenue for overcoming the energy conversion efficiency limits of conventional photoelectric devices utilizing p-n junction architectures. To facilitate effective photocarrier separation and enhance the APE, polar materials need to be thinned down to maximize the depolarization field. Here, we demonstrate Janus MoSSe monolayers (~0.67 nm thick) with strong spontaneous photocurrent generation. A photoresponsivity up to 3 mA/W, with ~ 1% external quantum efficiency and ultrafast photoresponse (~50 ps) were observed in the MoSSe device. Moreover, unlike conventional 2D materials that require careful twist alignment, the photovoltage can be further scaled up by simply stacking the MoSSe layers without the need for specific control on interlayer twist angles. Our work paves the way for the development of high-performance, flexible, and compact photovoltaics and optoelectronics with atomically engineered Janus polar materials., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Protein lactylation is an emerging field. To advance the exploration of its biological functions, here we develop a comprehensive workflow that integrates proteomics to identify lactylated sites, genetic code expansion (GCE) for the expression of site-specifically lactylated proteins in living cells, and an integrated functional analysis (IFA) platform to evaluate their biological effects. Using a combined wet-and-dry-lab proteomics strategy, we identify a conserved lactylation at ALDOA-K147, which we hypothesize plays a significant biological role. Expression of this site-specifically lactylated ALDOA in mammalian cells reveals that this modification not only inhibits enzymatic activity but also induces gain-of-function effects. These effects reshaped ALDOA functionality by enhancing protein stability, promoting nuclear translocation, regulating adhesion-related gene expression, altering cell morphology and modulating ALDOA-interacting proteins. Our findings highlight the utility of the GCE-based workflow in establishing causal relationships between specific lactylation events and both target-specific and cell-wide changes, advancing our understanding of protein lactylation's functional impact., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Diagnosing lung cancer from indeterminate pulmonary nodules (IPLs) remains challenging. In this multi-institutional study involving 2032 participants with IPLs, we integrate the clinical, radiomic with circulating cell-free DNA fragmentomic features in 5-methylcytosine (5mC)-enriched regions to establish a multiomics model (clinic-RadmC) for predicting the malignancy risk of IPLs. The clinic-RadmC yields an area-under-the-curve (AUC) of 0.923 on the external test set, outperforming the single-omics models, and models that only combine clinical features with radiomic, or fragmentomic features in 5mC-enriched regions (p < 0.050 for all). The superiority of the clinic-RadmC maintains well even after adjusting for clinic-radiological variables. Furthermore, the clinic-RadmC-guided strategy could reduce the unnecessary invasive procedures for benign IPLs by 10.9% ~ 35%, and avoid the delayed treatment for lung cancer by 3.1% ~ 38.8%. In summary, our study indicates that the clinic-RadmC provides a more effective and noninvasive tool for optimizing lung cancer diagnoses, thus facilitating the precision interventions., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Iron alloys, including steels and magnetic functional materials, are widely used in capital construction, manufacturing, electromagnetic technology, etc. However, they face the long-standing challenge of high coefficient of thermal expansion (CTE), limiting the applications in high-precision fields. This work proposes a strategy involving the in-situ formation of a nano-scale lamellar/labyrinthine negative thermal expansion (NTE) phase within the iron matrix to tackle this problem. For example, a model alloy, Fe-Zr10-Nb6, was synthesized and its CTE is reduced to approximately half of the iron matrix. Meanwhile, the alloy possesses a strength-plasticity combination of 1.5 GPa (compressive strength) and 17.5% (ultimate strain), which outperforms other low thermal expansion (LTE) metallic materials. The magnetovolume effect of the NTE phase is deemed to counteract the positive thermal expansion in iron. The high stress-carrying hard NTE phase and the tough matrix synergistically contribute to the high mechanical properties. The interaction between the slip of lamellar microstructure and the slip-hindering of labyrinthine microstructure further enhances the strength-plasticity combination. This work shows the promise of offering a method to produce LTE iron alloys with high mechanical properties., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins are the minimal machinery required for vesicle fusion in eukaryotes. Formation of a highly stable four-helix bundle consisting of SNARE motif of these proteins, drives vesicle/membrane fusion involved in several physiological processes such as neurotransmission. Recycling/disassembly of the protein machinery involved in membrane fusion is essential and is facilitated by an AAA+ ATPase, N-ethylmaleimide sensitive factor (NSF) in the presence of an adapter protein, α-SNAP. Here we use single-molecule fluorescence spectroscopy approaches to elucidate the chain of events that occur during the disassembly of SNARE complex by NSF. Our observations indicate two major pathways leading to the sequential disassembly of the SNARE complex: one where a syntaxin separated intermediate state is observed before syntaxin disassembles first, and a second where Vamp disassembles from the other proteins first. These studies uncover two parallel sequential pathways for the SNARE disassembly by NSF along with a syntaxin separated intermediate that couldn't be observed otherwise., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Metabolic reprogramming fuels cancer cell metastasis and remodels the immunosuppressive tumor microenvironment (TME). We report here that circPETH, a circular RNA (circRNA) transported via extracellular vesicles (EVs) from tumor-associated macrophages (TAMs) to hepatocellular carcinoma (HCC) cells, facilitates glycolysis and metastasis in recipient HCC cells. Mechanistically, circPETH-147aa, encoded by circPETH in an m6A-driven manner, promotes PKM2-catalyzed ALDOA-S36 phosphorylation via the MEG pocket. Furthermore, circPETH-147aa impairs anti-HCC immunity by increasing HuR-dependent SLC43A2 mRNA stability and driving methionine and leucine deficiency in cytotoxic CD8 + T cells. Importantly, through virtual and experimental screening, we find that a small molecule, Norathyriol, is an effective inhibitor that targets the MEG pocket on the circPETH-147aa surface. Norathyriol reverses circPETH-147aa-facilitated acquisition of metabolic and metastatic phenotypes by HCC cells, increases anti-PD1 efficacy, and enhances cytotoxic CD8 + T-cell function. Here we show that Norathyriol is a promising anti-HCC agent that contributes to attenuating the resistance of advanced HCC to immune checkpoint blocker (ICB) therapies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Key functions of antibodies, such as viral neutralisation, depend on high-affinity binding. However, viral neutralisation poorly correlates with antigen affinity for reasons that have been unclear. Here, we use a new mechanistic model of bivalent binding to study  >45 patient-isolated IgG1 antibodies interacting with SARS-CoV-2 RBD surfaces. The model provides the standard monovalent affinity/kinetics and new bivalent parameters, including the molecular reach: the maximum antigen separation enabling bivalent binding. We find large variations in these parameters across antibodies, including reach variations (22-46 nm) that exceed the physical antibody size (~15 nm). By using antigens of different physical sizes, we show that these large molecular reaches are the result of both the antibody and antigen sizes. Although viral neutralisation correlates poorly with affinity, a striking correlation is observed with molecular reach. Indeed, the molecular reach explains differences in neutralisation for antibodies binding with the same affinity to the same RBD-epitope. Thus, antibodies within an isotype class binding the same antigen can display differences in molecular reach, substantially modulating their binding and functional properties., Competing Interests: Competing interests: G.R.S. is on the GSK Vaccines Scientific Advisory Board, a founder shareholder of RQ Biotechnology, and a Jenner investigator. Oxford University holds intellectual property related to the Oxford-AstraZeneca vaccine. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Aqueous zinc ion batteries exhibit great prospects due to their low cost and high safety, while their lifespan is limited by severe dendritic growth problems. Herein, we develop an anti-dendrite hot-pressing separator interlayer through a mass-producible hot-pressing strategy, by spreading metal-organic framework (MOF) precursor on nonwoven matrix followed by a simple hot-pressing process. The in situ modification of MOF crystals on fiber surface processes abundant nitrogenous functional groups and high specific surface area (190.8 m 2 g -1 ) with a strong attraction to Zn 2+ . These features contribute to a staged deposition behavior to promote uniform nucleation at high concentrations and two-dimensional grain growth at low concentrations. Consequently, Zn | |Zn symmetrical cells with hot-pressing separator interlayer demonstrate cycle lives of 3000 hours at 2 mA cm -2 , 2 mAh cm -2 . Moreover, Zn | |I 2 pouch batteries with hot-pressing separator interlayer realizes 840 cycles lifespan with a capacity retention of 90.9% and a final discharge capacity of 110.6 mAh at 25 °C., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The recently emerged remote epitaxy technique, utilizing 2D materials (mostly graphene) as interlayers between the epilayer and the substrate, enables the exfoliation of crystalline nanomembranes from the substrate, expanding the range of potential device applications. However, remote epitaxy has been so far applied to a limited range of material systems, owing to the need of stringent growth conditions to avoid graphene damaging, and has therefore remained challenging for the synthesis of oxide nanomembranes. Here, we demonstrate the remote epitaxial growth of an oxide nanomembrane (vanadium dioxide, VO 2 ) with a sub-nanometer thick amorphous interlayer, which can withstand potential sputtering-induced damage and oxidation. By removing the amorphous interlayer, a 4-inch wafer-scale freestanding VO 2 nanomembrane can be obtained, exhibiting intact crystalline structure and physical properties. In addition, multi-shaped freestanding infrared bolometers are fabricated based on the epitaxial VO 2 nanomembranes, showing high detectivity and low current noise. Our strategy provides a promising way to explore various freestanding heteroepitaxial oxide materials for future large-scale integrated circuits and functional devices., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

AgSbTe 2 is a promising p-type thermoelectric material operating in the mid-temperature regime. To further enhance its thermoelectric performance, previous research has mainly focused on reducing lattice thermal conductivity by forming ordered nanoscale domains for instance. However, the relatively low power factor is the main limitation affecting the power density of AgSbTe 2 -based thermoelectric devices. In this work, we demonstrate that hole-doped AgSbTe 2 with Sn induces the formation of a new impurity band just above the valence band maximum. This approach significantly improves the electrical transport properties, contrary to previous strategies that focused on reducing lattice thermal conductivity. As a result, we achieve a record-high power factor of 27 μWcm -1 K -2 and a peak thermoelectric figure of merit zT of 2.5 at 673 K. This exceptional performance is attributed to an increased hole concentration resulting from the formation of the impurity band and a lower formation energy of the defect complexes ( V A g 1 -  +  S n S b 1 - ). Besides, the doped materials exhibit a significantly improved Seebeck coefficient by inhibiting bipolar conductivity and preventing the formation of n-type Ag 2 Te. Additionally, the optimized AgSbTe 2 is used to fabricate a unicouple thermoelectric device that achieves energy conversion efficiencies of up to 12.1% and a high power density of 1.13 Wcm -2 . This study provides critical insights and guidance for optimizing the performance of p-type AgSbTe 2 in thermoelectric applications., Competing Interests: Competing interests: One Chinese patent application (202410992695X) was filed by Y.Z. and T.Z. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Peptide sequencing via tandem mass spectrometry (MS/MS) is essential in proteomics. Unlike traditional database searches, deep learning excels at de novo peptide sequencing, even for peptides missing from existing databases. Current deep learning models often rely on autoregressive generation, which suffers from error accumulation and slow inference speeds. In this work, we introduce π-PrimeNovo, a non-autoregressive Transformer-based model for peptide sequencing. With our architecture design and a CUDA-enhanced decoding module for precise mass control, π-PrimeNovo achieves significantly higher accuracy and up to 89x faster inference than state-of-the-art methods, making it ideal for large-scale applications like metaproteomics. Additionally, it excels in phosphopeptide mining and detecting low-abundance post-translational modifications (PTMs), marking a substantial advance in peptide sequencing with broad potential in biological research., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Somatic variations can give rise to bud sports with advantageous traits, serving as the foundation for bud sport breeding in perennial plants. Here, we report a fully phased genome assembly of 'Fuji' apple, enabling comprehensive identification of somatic variants across 74 clonally propagated 'Fuji' varieties. Phylogenetic analysis indicates that spur-type and early-maturation traits in 'Fuji' sport varieties arise from multiple independent events. Several putative functional somatic variants have been identified, including a spur-type-specific deletion in the promoter of the TCP transcription factor gene MdTCP11. DNA methylation level of the deletion-associated miniature inverted-repeat transposable element is lower in spur-type varieties compared to standard-type varieties, while the expression of MdTCP11 is significantly higher. Overexpression of MdTCP11 in apple decreases plant height, highlighting its important role in the development of spur-type apple varieties. This study sheds light on the cloning history of 'Fuji' and provides valuable resources for apple breeding., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Magnetic resonance imaging contrast agents can enhance diagnostic precision but often face limitations such as short imaging windows, low tissue specificity, suboptimal contrast enhancement, or potential toxicity, which affect resolution and long-term monitoring. Here, we present a protein contrast agent based on lanmodulin, engineered with a single-point mutation at position 108 from N to D to yield maximum gadolinium binding sites. After loading with Gd 3+ ions, the resulting protein complex, LanND-Gd, exhibits efficient renal clearance, high relaxivity, and prolonged renal retention compared to commercial agents. LanND-Gd enables high-performance visualization of whole-body structures and brain vasculature in male mice at a resolution finer than one hundred micrometers. In male ischemia mouse models, LanND-Gd also improves kidney dysfunction monitoring while minimizing risks of neural toxicity or immunogenic reactions. This protein-based contrast agent offers superior image quality, improved biocompatibility, and extended imaging timeframes, promising significant advancements in magnetic resonance-based diagnostics and patient outcomes., Competing Interests: Competing interests X.L., Y.L., and Z.L. are co-inventors on a Singapore patent application related to the use of lanmodulin-derived contrast agents for magnetic resonance imaging (application no. 10202400550P), filed by the National University of Singapore. The other authors declare no competing interests., (© 2024. The Author(s).)

The burgeoning interest in two-dimensional semiconductors stems from their potential as ultrathin platforms for next-generation transistors. Nonetheless, there persist formidable challenges in fully obtaining high-performance complementary logic components and the underlying mechanisms for the polarity modulation of transistors are not yet fully understood. Here, we exploit both ferroelectric domain-based nonvolatile modulation of Fermi level in transitional metal dichalcogenides (MoS 2 ) and quantum tunneling through nanoscale hexagonal boron nitride (h-BN). Our prototype devices, termed as vertical tunneling ferroelectric field-effect transistor, utilizes a Van der Waals MoS 2 /h-BN/metal tunnel junction as the channel. The Fermi level of MoS 2 is bipolarly tuned by ferroelectric domains and sensitively detected by the direct quantum tunneling strength across the junction, demonstrating an impressive electroresistance ratio of up to 10 9 in the vertical tunneling ferroelectric field-effect transistor. It consumes only 0.16 fJ of energy to open a ratio window exceeding 10 4 . This work not only validates the effectiveness of tailored tunnel barriers in manipulating electronic flow but also highlights a new avenue for the design flexibility and functional versatility of advanced ferroelectric memory technology., (© 2024. The Author(s).)

mRNA therapeutics are set to revolutionize disease prevention and treatment, inspiring the development of platforms for safe and effective mRNA delivery. However, current mRNA delivery platforms face some challenges, including limited organ tropism for nonvaccine applications and inflammation induced by cationic nanoparticle components. Herein, we address these challenges through a versatile, noncationic nanoparticle platform whereby mRNA is assembled into a poly(ethylene glycol)-polyphenol network stabilized by metal ions. Screening a range of components and relative compositional ratios affords a library of stable, noncationic, and highly biocompatible metal-organic nanoparticles with robust mRNA transfection in vitro and in mice. Intravenous administration of the lead mRNA-containing metal-organic nanoparticles enables predominant protein expression and gene editing in the brain, liver, and kidney, while organ tropism is tuned by varying nanoparticle composition. This study opens an avenue for realizing metal-organic nanoparticle-enabled mRNA delivery, offering a modular approach to assembling mRNA therapeutics for health applications., (© 2024. The Author(s).)

Aryl thianthrenium salts are valuable in photocatalysis but traditionally require external electron donors for activation. This study introduces an energy transfer (EnT) strategy for the activation of aryl thianthrenium salts using 2,3,4,5,6-penta(carbazol-9-yl)benzonitrile (5CzBN) as a metal-free photocatalyst, eliminating the need for external donors. Utilizing this EnT approach, we achieve C-H deuteration of arenes under visible light with CDCl 3 as a deuterium source to synthesize various deuterated aromatic compounds, including important natural products and pharmaceuticals. Additionally, this strategy enables diverse functionalizations including borylation, arylation, cyanation, and selenylation, enhancing the applicability of aryl sulfonium salts in environmentally friendly photocatalysis., (© 2024. The Author(s).)

Nuclear three dimensional (3D) folding of chromatin structure has been linked to gene expression regulation and correct developmental programs, but little is known about the 3D architecture of sex chromosomes within the nucleus, and how that impacts their role in sex determination. Here, we determine the sex-specific 3D organization of the model brown alga Ectocarpus chromosomes at 2 kb resolution, by mapping long-range chromosomal interactions using Hi-C coupled with Oxford Nanopore long reads. We report that Ectocarpus interphase chromatin exhibits a non-Rabl conformation, with strong contacts among telomeres and among centromeres, which feature centromere-specific LTR retrotransposons. The Ectocarpus chromosomes do not contain large local interactive domains that resemble TADs described in animals, but their 3D genome organization is largely shaped by post-translational modifications of histone proteins. We show that the sex determining region (SDR) within the U and V chromosomes are insulated and span the centromeres and we link sex-specific chromatin dynamics and gene expression levels to the 3D chromatin structure of the U and V chromosomes. Finally, we uncover the unique conformation of a large genomic region on chromosome 6 harboring an endogenous viral element, providing insights regarding the impact of a latent giant dsDNA virus on the host genome's 3D chromosomal folding., (© 2024. The Author(s).)

Magnesium (Mg) metal is a promising anode candidate for high-energy and cost-effective multivalent metal batteries, but suffers from severe surface passivation in conventional electrolytes, especially aqueous solutions. Here, we uncover that MgH 2 , in addition to the well-known MgO and Mg(OH) 2 , can be formed during the passivation of Mg by water. The formation mechanism and spatial distribution of MgH 2 , and its detrimental effect on interfacial dynamics and stability of Mg anode are revealed by comprehensive experimental and theoretical investigations. Furthermore, a graphite-based hydrophobic and Mg 2+ -permeable water-tolerant interphase is drawn using a pencil on the surface of Mg anodes, allowing them to cycle stably in symmetric (> 900 h) and full cells (> 500 cycles) even after contact with water. The mechanistic understanding of MgH 2 -involved Mg passivation and the design of pencil-drawn waterproof Mg anodes may inspire the further development of Mg metal batteries with high water resistance., (© 2024. The Author(s).)

In eukaryotes, topologically associating domains (TADs) organize the genome into functional compartments. While TAD-like structures are common in mammals and many plants, they are challenging to detect in Arabidopsis thaliana. Here, we demonstrate that Arabidopsis PDS5 proteins play a negative role in TAD-like domain formation. Through Hi-C analysis, we show that mutations in PDS5 genes lead to the widespread emergence of enhanced TAD-like domains throughout the Arabidopsis genome, excluding pericentromeric regions. These domains exhibit increased chromatin insulation and enhanced chromatin interactions, without significant changes in gene expression or histone modifications. Our results suggest that PDS5 proteins are key regulators of genome architecture, influencing 3D chromatin organization independently of transcriptional activity. This study provides insights into the unique chromatin structure of Arabidopsis and the broader mechanisms governing plant genome folding., (© 2024. The Author(s).)

Grain boundary hardening and precipitation hardening are important mechanisms for enhancing the strength of metals. Here, we show that these two effects can be amplified simultaneously in nanocrystalline compositionally complex alloys (CCAs), leading to near-theoretical strength and large deformability. We develop a model nanograined (TiZrNbHf) 98 Ni 2 alloy via thermodynamic design. The Ni solutes, which has a large negative mixing enthalpy and different electronegativity to Ti, Zr, Nb and Hf, not only produce Ni-enriched local chemical inhomogeneities in the nanograins, but also segregate to grain boundaries. The resultant alloy achieves a 2.5 GPa yield strength, together with work hardening capability and large homogeneous deformability to 65% compressive strain. The local chemical inhomogeneities impede dislocation propagation and encourage dislocation multiplication to promote strain hardening. Meanwhile, Ni segregates to grain boundaries and enhances cohesion, suppressing the grain growth and grain boundary cracking found while deforming the reference TiZrNbHf alloy. Our alloy design strategy thus opens an avenue, via solute decoration at grain boundaries combined with local chemical inhomogeneities inside the grains, towards ultrahigh strength and large plasticity in nanostructured alloys., (© 2024. The Author(s).)

Chickens are the most abundant agricultural animals globally, with controlling abdominal fat deposition being a key objective in poultry breeding. While GWAS can identify genetic variants associated with abdominal fat deposition, the precise roles and mechanisms of these variants remain largely unclear. Here, we use male chickens from two lines divergently selected for abdominal fat deposition as experimental models. Through the integration of genomic, epigenomic, 3D genomic, and transcriptomic data, we build a comprehensive chromatin 3D regulatory network map to identify the genetic regulatory mechanisms that influence abdominal fat deposition in chickens. Notably, we find that the rs734209466 variant functions as an allele-specific enhancer, remotely enhancing the transcription of IGFBP2 and IGFBP5 by the binding transcription factor IRF4. This interaction influences the differentiation and proliferation of preadipocytes, which ultimately affects phenotype. This work presents a detailed genetic regulatory map for chicken abdominal fat deposition, offering molecular targets for selective breeding., (© 2024. The Author(s).)

The anterior cruciate ligament is anchored to the femur and tibia via specialized interfaces known as entheses. These play a critical role in ligament homeostasis and joint stability by transferring forces, varying in magnitude and direction between structurally and functionally dissimilar tissues. However, the precise structural and mechanical characteristics underlying the femoral and tibial entheses and their intricate interplay remain elusive. In this study, two thin-graduated mineralization regions in the femoral enthesis (~21 μm) and tibial enthesis (~14 μm) are identified, both exhibiting distinct biomolecular compositions and mineral assembly patterns. Notably, the femoral enthesis interface exhibits progressively maturing hydroxyapatites, whereas the mineral at the tibial enthesis interface region transitions from amorphous calcium phosphate to hydroxyapatites with increasing crystallinity. Proteomics results reveal that Matrix Gla protein uniquely enriched at the tibial enthesis interface, may stabilize amorphous calcium phosphate, while C-type lectin domain containing 11 A, enriched at the femoral enthesis interface, could facilitate the interface mineralization. Moreover, the finite element analysis indicates that the femoral enthesis model exhibited higher resistance to shearing, whereas the tibial enthesis model contributes to tensile resistance, suggesting that the discrepancy in biomolecular expression and the corresponding mineral assembly heterogeneities collectively contribute to the superior mechanical properties of both the femoral enthesis and tibial enthesis models. These findings provide novel perspectives on the structure-function relationships of anterior cruciate ligament entheses, paving the way for improved management of anterior cruciate ligament injury and regeneration., (© 2024. The Author(s).)

Resilience, the ability to maintain fundamental functionality amidst failures and errors, is crucial for complex networked systems. Most analytical approaches rely on predefined equations for node activity dynamics and simplifying assumptions on network topology, limiting their applicability to real-world systems. Here, we propose ResInf, a deep learning framework integrating transformers and graph neural networks to infer resilience directly from observational data. ResInf learns representations of node activity dynamics and network topology without simplifying assumptions, enabling accurate resilience inference and low-dimensional visualization. Experimental results show that ResInf significantly outperforms analytical methods, with an F1-score improvement of up to 41.59% over Gao-Barzel-Barabási framework and 14.32% over spectral dimension reduction. It also generalizes to unseen topologies and dynamics and maintains robust performance despite observational disturbances. Our findings suggest that ResInf addresses an important gap in resilience inference for real-world systems, offering a fresh perspective on incorporating data-driven approaches to complex network modeling., (© 2024. The Author(s).)

We present SpliceTransformer (SpTransformer), a deep-learning framework that predicts tissue-specific RNA splicing alterations linked to human diseases based on genomic sequence. SpTransformer outperforms all previous methods on splicing prediction. Application to approximately 1.3 million genetic variants in the ClinVar database reveals that splicing alterations account for 60% of intronic and synonymous pathogenic mutations, and occur at different frequencies across tissue types. Importantly, tissue-specific splicing alterations match their clinical manifestations independent of gene expression variation. We validate the enrichment in three brain disease datasets involving over 164,000 individuals. Additionally, we identify single nucleotide variations that cause brain-specific splicing alterations, and find disease-associated genes harboring these single nucleotide variations with distinct expression patterns involved in diverse biological processes. Finally, SpTransformer analysis of whole exon sequencing data from blood samples of patients with diabetic nephropathy predicts kidney-specific RNA splicing alterations with 83% accuracy, demonstrating the potential to infer disease-causing tissue-specific splicing events. SpTransformer provides a powerful tool to guide biological and clinical interpretations of human diseases., (© 2024. The Author(s).)

The immune checkpoint receptor, programmed cell death 1 (PD-1, encoded by PDCD1), mediates the immune escape of cancer, but whether PD-1 splicing isoforms contribute to this process is still unclear. Here, we identify an alternative splicing isoform of human PD-1, which carries a 28-base pairs extension retained from 5' region of intron 2 (PD-1^28), is expressed in peripheral T cells and tumor infiltrating lymphocytes. PD-1^28 expression is induced on T cells upon activation and is regulated by an RNA binding protein, TAF15. Functionally, PD-1^28 inhibits T cell proliferation, cytokine production, and tumor cell killing in vitro. In vivo, T cell-specific exogenous expression of PD-1^28 promotes tumor growth in both a syngeneic mouse tumor model and humanized NOG mice inoculated with human lung cancer cells. Our study thus demonstrates that PD-1^28 functions as an immune checkpoint, and may contribute to resistance to immune checkpoint blockade therapy., (© 2024. The Author(s).)

Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear. The generation of large extracellular vesicles (EVs) has emerged as a key mechanism for the removal of cellular waste from cells that are dying or stressed. Here, we used intravital microscopy of the bone marrow to directly measure the kinetics of EV formation from endothelial cells in vivo under homoeostatic and malignant conditions. These large EVs are mitochondria-rich, expose the 'eat me' signal phosphatidylserine, and can interact with immune cell populations as a potential clearance mechanism. Elevated levels of circulating EVs correlates with degradation of the bone marrow vasculature caused by acute myeloid leukaemia. Together, our study provides in vivo spatio-temporal characterization of EV formation in the murine vasculature and suggests that circulating, large endothelial cell-derived EVs can provide a snapshot of vascular damage at distal sites., (© 2024. The Author(s).)

Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-COV-2, Influenza A, B, and respiratory syncytial virus with a sensitivity of 10 copies/mL. When integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single-copy spatial resolution of 0.83 copies/m 3 for airborne virus surveillance with an air flow rate of 400 L/min and a sampling time of 30 minutes. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission., (© 2024. The Author(s).)