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Machine learning is the core of artificial intelligence. Using optical signals for training and converting them into electrical signals for inference, combines the strengths of both, and thus can greatly improve machine learning efficiency. Optoelectronic memories are the hardware foundation for this strategy. However, the existing optoelectronic memories cannot modulate a large number of non-volatile resistive states using ultra-short and ultra-dim light pulses, leading to low training accuracy, slow computing speed and high energy consumption. Here, we synthesized a van der Waals layered photoconductive material, (NH 4 )BiI 3 , with excellent photoconductivity and strong dielectric screening effect. We further employed it as the photosensitive control gate in a floating-gate transistor, replacing the commonly used metal control gate, to construct an optical floating gate transistor which achieves adjustable synaptic weights under ultra-dim light without gate voltage assistance. Moreover, it shows ultra-low training energy consumption to generate a non-volatile state and the largest resistive state numbers among the known non-volatile optoelectronic memories. These exceptional performances enable the construction of one-transistor-one-memory device arrays to achieve ~99% accuracy in Artificial Neural Networks. Moreover, the device arrays can match the performance of GPU in YOLOv8 while greatly reducing energy consumption., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The self-assembly of small molecules through non-covalent interactions is an emerging and promising strategy for building dynamic, stable, and large-scale structures. One remaining challenge is making the non-covalent interactions occur in the ideal positions to generate strength comparable to that of covalent bonds. This work shows that small molecule YAWF can self-assemble into a liquid-crystal hydrogel (LCH), the mechanical properties of which could be controlled by water. LCH can be used to construct stable solid threads with a length of over 1 meter by applying an external force on 2 µL of gel solution followed by water-regulated crystallization. These solid threads can support 250 times their weight. Cryogenic electron microscopy (Cryo-EM) analysis unravels the three-dimensional structure of the liquid-crystal fiber (elongated helix with C2 symmetry) at an atomic resolution. The multiscale mechanics of this material depend on the specificity of the molecular structure, and the water-controlled hierarchical and sophisticated self-assembly., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Ovarian function declines significantly as females enter middle-age, but the mechanisms underlying this decline remain unclear. Here, we utilize whole-organ imaging to observe a notable decrease in ovarian blood vessel (oBV) density and angiogenesis intensity of middle-aged mice. This leads to a diminished blood supply to the ovaries, resulting in inadequate development and maturation of ovarian follicles. Utilizing genetic-modified mouse models, we demonstrate that granulosa cell secreted VEGFA governs ovarian angiogenesis, but the physiological decline in oBV is not attributed to VEGFA insufficiency. Instead, through single-cell sequencing, we identify the aging of the ovarian vascular endothelium as the primary factor contributing to oBV decline. Consequently, the administration of salidroside, a natural compound that is functional to reverse oBV aging and promote ovarian angiogenesis, significantly enhances ovarian blood supply and improve fertility in older females. Our findings highlight that enhancing oBV function is a promising strategy to boost fertility in females., Competing Interests: Competing interests: The author declares no competing interests., (© 2024. The Author(s).)

Controllable engineering of thin lithium (Li) metal is essential for increasing the energy density of solid-state batteries and clarifying the interfacial evolution mechanisms of a lithium metal negative electrode. However, fabricating a thin lithium electrode faces significant challenges due to the fragility and high viscosity of Li metal. Herein, through facile treatment of Ta-doped Li 7 La 3 Zr 2 O 12 (LLZTO) with trifluoromethanesulfonic acid, its surface Li 2 CO 3 species is converted into a lithiophilic layer with LiCF 3 SO 3 and LiF components. It enables the thickness control of Li metal negative electrodes, ranging from 0.78 μm to 30 μm. Quasi-solid-state lithium-metal battery with an optimized 7.54 μm-thick lithium metal negative electrode, a commercial LiNi 0.83 Co 0.11 Mn 0.06 O 2 positive electrode, and a negative/positive electrode capacity ratio of 1.1 shows a 500 cycles lifespan with a final discharge specific capacity of 99 mAh g -1 at 2.35 mA cm -2 and 25 °C. Through multi-scale characterizations of the thin lithium negative electrode, we clarify the multi-dimensional compositional evolution and failure mechanisms of lithium-deficient and -rich regions (0.78 μm and 7.54 μm), on its surface, inside it, or at the Li/LLZTO interface., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The energy industry has taken notice of zinc-iodine (Zn-I 2 ) batteries for their high safety, low cost, and attractive energy density. However, the shuttling of I 3 - by-products at cathode electrode and dendrite issues at Zn metal anode result in short cycle lifespan. Here, a tripartite synergistic optimization strategy is proposed, involving a MXene cathode host, a n-butanol electrolyte additive, and the in-situ solid electrolyte interface (SEI) protection. The MXene possesses catalytic ability to enhance the reaction kinetics and reduce I 3 - by-products. Meanwhile, the partially dissolved n-butanol additive can work synergistically with MXene to inhibit the shuttling of I 3 - . Besides, the n-butanol and I - in the electrolyte can synergistically improve the solvation structure of Zn 2+ . Moreover, an organic-inorganic hybrid SEI is in situ generated on the surface of the Zn anode, which induces stable non-dendritic zinc deposition. As a result, the fabricated batteries exhibit a high capacity of 0.30 mAh cm -2 and a superior energy density of 0.34 mWh cm -2 at a high specific current of 5 A g -1 across 30,000 cycles, with a minimal capacity decay of 0.0004% per cycle. This work offers a promising strategy for the subsequent research to comprehensively improve battery performance., (© 2024. The Author(s).)

Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employ an icosahedral DNA origami (ICO) as a display particle for RBD nanovaccines, achieving morphology and diameter like the virus (91 ± 11 nm). The surface addressability of DNA origami permits facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoke stronger and more enduring humoral and T cell immune responses in female mouse models compared to soluble RBD antigens, and the multivalent display broaden the protection range of B cell responses to more mutant strains. Our vaccines activate similar humoral immunity, observable stronger cellular immunity and more memory immune cells compared to trimeric mRNA vaccines., (© 2024. The Author(s).)

Tin-based perovskite solar cells have garnered attention for their biocompatibility, narrow bandgap, and long thermal carrier lifetime. However, nip-type tin-based perovskite solar cells have underperformed largely due to the indiscriminate use of metal oxide electron transport layers originally designed for nip-type lead-based perovskite solar cells. Here, we reveal that this underperformance is caused by oxygen vacancies and deeper energy levels in metal oxide. To address these issues, we propose a metal chalcogenide electron transport layer, specifically Sn(S 0.92 Se 0.08 ) 2 , which circumvents the oxygen molecules desorption and impedes the Sn 2+ oxidation. As a result, tin-based perovskite solar cells with Sn(S 0.92 Se 0.08 ) 2 demonstrate a V OC increase from 0.48 - 0.73 V and a power conversion efficiency boost from 6.98 - 11.78%. Additionally, these cells exhibit improved stability, retaining over 95% of their initial efficiency after 1632 h. Our findings showcase metal chalcogenides as promising candidates for future nip-type tin-based perovskite solar cell applications., (© 2024. The Author(s).)

Sir2-HerA is a widely distributed antiphage system composed of a RecA-like ATPase (HerA) and an effector with potential NADase activity (Sir2). Sir2-HerA is believed to provide defense against phage infection in Sir2-dependent NAD + depletion to arrest the growth of infected cells. However, the detailed mechanism underlying its antiphage activity remains largely unknown. Here, we report functional investigations of Sir2-HerA from Staphylococcus aureus (SaSir2-HerA), unveiling that the NADase function of SaSir2 can be allosterically activated by the binding of SaHerA, which then assembles into a supramolecular complex with NADase activity. By combining the cryo-EM structure of SaSir2-HerA in complex with the NAD + cleavage product, it is surprisingly observed that Sir2 protomers that interact with HerA are in the activated state, which is due to the opening of the α15-helix covering the active site, allowing NAD + to access the catalytic pocket for hydrolysis. In brief, our study provides a comprehensive view of an allosteric activation mechanism for Sir2 NADase activity in the Sir2-HerA immune system., (© 2024. The Author(s).)

Taste, a pivotal sense modality, plays a fundamental role in discerning flavors and evaluating the potential harm of food, thereby contributing to human survival, physical and mental health. Patients with tongue cancer may experience a loss of taste following extensive surgical resection with flap reconstruction. Here, we designed a gustatory interface that enables the non-invasive detection of tongue electrical activities for a comprehensive operative assessment. Moreover, it decodes gustatory information from the reconstructed tongue without taste buds. Our gustatory interface facilitates the recording and analysis of electrical activities on the tongue, yielding an electrical mapping across the entire tongue surface, which delineates the safe margin for surgical management and assesses flap viability for postoperative structure monitoring and prompt intervention. Furthermore, the gustatory interface helps patients discern tastes with an accuracy of 97.8%. Our invention offers a promising approach to clinical assessment and management and holds potential for improving the quality of life for individuals with tongue cancer., (© 2024. The Author(s).)

Sea cucumbers are predominant deposit feeders in benthic ecosystems, providing protective benefits to coral reefs by reducing disease prevalence. However, how they receive sufficient nutrition from seabed sediments remains poorly understood. Here, we investigate Holothuria leucospilota, an ecologically significant tropical sea cucumber, to elucidate digestive mechanisms underlying marine deposit-feeding. Genomic analysis reveals intriguing evolutionary adaptation characterized by an expansion of digestive carbohydrase genes and a contraction of digestive protease genes, suggesting specialization in digesting microalgae. Developmentally, two pivotal dietary shifts, namely, from endogenous nutrition to planktonic feeding, and from planktonic feeding to deposit feeding, induce changes in digestive tract enzyme profiles, with adults mainly expressing carbohydrases and lipases. A nuanced symbiotic relationship exists between gut microbiota and the host, namely, specific resident bacteria supply crucial enzymes for food digestion, while other bacteria are digested and provide assimilable nutrients. Our study further identifies Holothuroidea lineage-specific lysozymes that are restrictedly expressed in the intestines to support bacterial digestion. Overall, this work advances our knowledge of the evolutionary innovations in the sea cucumber digestive system which enable them to efficiently utilize nutrients from seabed sediments and promote food recycling within marine ecosystems., (© 2024. The Author(s).)

Wearable thermoelectric generators provide a reliable power generation method for self-powered wearable electronic devices. However, there has been a lack of research regarding the comfort of wearable thermoelectric generators. Here we propose a design for a comfortable wearable thermoelectric generators system with high output power based on sandwiched thermoelectric model. This model paves the way for simultaneously optimizing comfort (skin temperature and pressure perception) and output power by systematically considering a variety of thermal resistive environments and bending states, the properties of the thermoelectric and encapsulation materials, and the device structure. To verify this strategy, we fabricate wearable thermoelectric generators using Mg-based thermoelectric materials. These materials have great potential for replacing traditional Bi 2 Te 3 -based materials and enable our wearable thermoelectric generators with a power density of 18.4 μWcm -2 under a wearing pressure of 0.8 kPa and with a skin temperature of 33 °C, ensuring the wearer's comfort., (© 2024. The Author(s).)

Owing to their capability to produce reactive oxygen species (ROS) under solar irradiation, covalent organic frameworks (COFs) with pre-designable structure and unique architectures show great potentials for water purification. However, the sluggish charge separation, inefficient oxygen activation and poor structure stability in COFs restrict their practical applications to decontaminate water. Herein, via a facile one-pot synthetic strategy, we show the direct conversion of reversible imine linkage into rigid thiazole linkage can adjust the π-conjugation and local charge polarization of skeleton to boost the exciton dissociation on COFs. The rigid linkage can also improve the robustness of skeleton and the stability of COFs during the consecutive utilization process. More importantly, the thiazole linkage in COFs with optimal C 2p states (COF-S) effectively increases the activities of neighboring benzene unit to directly modulate the O 2 -adsorption energy barrier and improve the ROS production efficiency, resulting in the excellent photocatalytic degradation efficiency of seven toxic emerging contaminants (e.g. degrading ~99% of 5 mg L -1 paracetamol in only 7 min) and effective bacterial/algal inactivation performance. Besides, COF-S can be immobilized in continuous-flow reactor and in enlarged reactor to efficiently eliminate pollutants under natural sunlight irradiation, demonstrating the feasibility for practical application., (© 2024. The Author(s).)

Filovirus-host interactions play important roles in all stages of the virus lifecycle. Here, we identify LATS1/2 kinases and YAP, key components of the Hippo pathway, as critical regulators of EBOV transcription and egress. Specifically, we find that when YAP is phosphorylated by LATS1/2, it localizes to the cytoplasm (Hippo "ON") where it sequesters VP40 to prevent egress. In contrast, when the Hippo pathway is "OFF", unphosphorylated YAP translocates to the nucleus where it transcriptionally activates host genes and promotes viral egress. Our data reveal that LATS2 indirectly modulates filoviral VP40-mediated egress through phosphorylation of AMOTp130, a positive regulator of viral egress, but more surprisingly that LATS1/2 kinases directly modulate EBOV transcription by phosphorylating VP30, an essential regulator of viral transcription. In sum, our findings highlight the potential to exploit the Hippo pathway/filovirus axis for the development of host-oriented countermeasures targeting EBOV and related filoviruses., (© 2024. The Author(s).)

Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ -10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3's role in EM pathogenesis., (© 2024. The Author(s).)

Thermal management emerges as a grand challenge of next-generation electronics. Efforts to develop compact, solid-state cooling devices have led to the exploration of the electrocaloric effect of ferroelectric polymers. Despite recent advances, the applications of electrocaloric polymers on electronics operating at elevated temperatures remain essentially unexplored. Here, we report that the ferroelectric polymer composite composed of highly-polarized barium strontium titanate nanofibers and electron-accepting [6,6] phenyl-C61-butyric acid methyl ester retains fast electrocaloric responses and stable cyclability at elevated temperatures. We demonstrate the effectiveness of electrocaloric cooling in a polymer composite for a pyroelectric energy harvesting device. The device utilizes a simulated central processing unit (CPU) as the heat source. Our results show that the device remains operational even when the CPU is overheated. Furthermore, we show that the composite functions simultaneously as a pyroelectric energy converter to harvest thermal energy from an overheated chip into electricity in the electrocaloric process. This work suggests a distinct approach for overheating protection and recycling waste heat of microelectronics., (© 2024. The Author(s).)

Electrocatalytic H 2 production from seawater, recognized as a promising technology utilizing offshore renewables, faces challenges from chloride-induced reactions and corrosion. Here, We introduce a catalytic surface where OH - dominates over Cl - in adsorption and activation, which is crucial for O 2 production. Our NiFe-based anode, enhanced by nearby Cr sites, achieves low overpotentials and selective alkaline seawater oxidation. It outperforms the RuO 2 counterpart in terms of lifespan in scaled-up stacks, maintaining stability for over 2500 h in three-electrode tests. Ex situ/in situ analyses reveal that Cr(III) sites enrich OH - , while Cl - is repelled by Cr(VI) sites, both of which are well-dispersed and close to NiFe, enhancing charge transfer and overall electrode performance. Such multiple effects fundamentally boost the activity, selectively, and chemical stability of the NiFe-based electrode. This development marks a significant advance in creating durable, noble-metal-free electrodes for alkaline seawater electrolysis, highlighting the importance of well-distributed catalytic sites., (© 2024. The Author(s).)

It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co 2+ -Na + combo. A commercial Ni foam sustains ampere-level current densities alternatingly during continuous electrolysis for 93.8 h in an acidic solution, whereas such a Ni foam is completely dissolved in ~2 h for conventional electrolysis conditions. The work not only explores an alternating electrolysis-based system, alkali metal cation-based catalytic systems, and alkali metal cation-based electrodeposition techniques, and beyond, but demonstrates the possibility of prolonged electrolysis by repeated deposition-dissolution processes. With enough adjustable experimental variables, the upper improvement limit in the electrode lifespan would be high., (© 2024. The Author(s).)

The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8 + T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting., (© 2024. The Author(s).)

Heterozygous loss-of-function mutations in the GRN gene are a major cause of hereditary frontotemporal dementia. The mechanisms linking frontotemporal dementia pathogenesis to progranulin deficiency are not well understood, and there is currently no treatment. Our strategy to prevent the onset and progression of frontotemporal dementia in patients with GRN mutations is to utilize small molecule positive regulators of GRN expression to boost progranulin levels from the remaining functional GRN allele, thus restoring progranulin levels back to normal within the brain. This work describes a series of blood-brain-barrier-penetrant small molecules which significantly increase progranulin protein levels in human cellular models, correct progranulin protein deficiency in Grn +/- mouse brains, and reverse lysosomal proteome aberrations, a phenotypic hallmark of frontotemporal dementia, more efficiently than the previously described small molecule suberoylanilide hydroxamic acid. These molecules will allow further elucidation of the cellular functions of progranulin and its role in frontotemporal dementia and will also serve as lead structures for further drug development., (© 2024. The Author(s).)

Adjusting decision-making under uncertain and dynamic situations is the hallmark of intelligence. It requires a system capable of converting feedback information to renew the internal value. The anterior cingulate cortex (ACC) involves in error and reward events that prompt switching or maintenance of current decision strategies. However, it is unclear whether and how the changes of stimulus-action mapping during behavioral adaptation are encoded, nor how such computation drives decision adaptation. Here, we tracked ACC activity in male mice performing go/no-go auditory discrimination tasks with manipulated stimulus-reward contingencies. Individual ACC neurons integrate the outcome information to the value representation in the next-run trials. Dynamic recruitment of them determines the learning rate of error-guided value iteration and decision adaptation, forming a non-linear feedback-driven updating system to secure the appropriate decision switch. Optogenetically suppressing ACC significantly slowed down feedback-driven decision switching without interfering with the execution of the established strategy., (© 2024. The Author(s).)

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19 +/- HuDEP2 cells and CD34 + cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia., (© 2024. The Author(s).)

Porous frameworks constructed via noncovalent interactions show wide potential in molecular separation and gas adsorption. However, it remains a major challenge to prepare these materials from low-symmetry molecular building blocks. Herein, we report a facile strategy to fabricate noncovalent porous crystals through modular self-assembly of a low-symmetry helicene racemate. The P and M enantiomers in the racemate first stack into right- and left-handed triangular prisms, respectively, and subsequently the two types of prisms alternatively stack together into a hexagonal network with one-dimensional channels with a diameter of 14.5 Å. Remarkably, the framework reveals high stability upon heating to 275 °C, majorly due to the abundant π-interactions between the complementarily engaged helicene building blocks. Such porous framework can be readily prepared by fast rotary evaporation, and is easy to recycle and repeatedly reform. The refined porous structure and enriched π-conjugation also favor the selective adsorption of a series of small molecules., (© 2024. The Author(s).)

High-sensitivity strain sensing elements with a wide strain range, fast response, high stability, and small sensing areas are desirable for constructing strain sensor arrays with high temporospatial resolution. However, current strain sensors rely on crack-based conductive materials having an inherent tradeoff between their sensing area and performance. Here, we present a molecular-level crack modulation strategy in which we use layer-by-layer assembly to introduce strong, dynamic, and reversible coordination bonds in an MXene and silver nanowire-matrixed conductive film. We use this approach to fabricate a crack-based stretchable strain sensor with a very small sensing area (0.25 mm 2 ). It also exhibits an ultrawide working strain range (0.001-37%), high sensitivity (gauge factor ~500 at 0.001% and >150,000 at 35%), fast response time, low hysteresis, and excellent long-term stability. Based on this high-performance sensing element and facile assembly process, a stretchable strain sensor array with a device density of 100 sensors per cm 2 is realized. We demonstrate the practical use of the high-density strain sensor array as a multichannel pulse sensing system for monitoring pulses in terms of their spatiotemporal resolution., (© 2024. The Author(s).)

Nanoplasmas induced by intense laser fields have attracted enormous attention due to their accompanied spectacular physical phenomena which are vigorously expected by the community of science and industry. For instance, the energetic electrons and ions produced in laser-driven nanoplasmas are significant for the development of compact beam sources. Nevertheless, effective confinement on the propagating charged particles, which was realized through magnetic field modulation and target structure design in big facilities, are largely absent in the microscopic regime. Here we introduce a reliable scheme to provide control on the emission direction of protons generated from surface ionization in gold nanoparticles driven by intense femtosecond laser fields. The ionization level of the nanosystem provides us a knob to manipulate the characteristics of the collective proton emission. The most probable emission direction can be precisely steered by tuning the excitation strength of the laser pulses. This work opens new avenue for controlling the ion emission in nanoplasmas and can vigorously promote the fields such as development of on-chip beam sources at micro-/nano-scales., (© 2024. The Author(s).)

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation., (© 2024. The Author(s).)

Developing mild photocatalytic bromination strategies using sustainable bromo source has been attracting intense interests, but there is still much room for improvement. Full utilization of redox centers of photocatalysts for efficient generation of Br + species is the key. Herein we report heterogenous organophotocatalytic HBr oxidation coupled with oxygen reduction to furnish Br 2 and H 2 O 2 for effective bromination of arenes over Al 2 O 3 supported perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). Mechanism studies suggest that O-vacancy in Al 2 O 3 can provide Lewis-acid-type anchoring sites for O 2 , enabling unexpected dual-electron transfer from anchored photoexcited PTCDA to chemically bound O 2 to produce H 2 O 2 . The in-situ generated H 2 O 2 and Br 2 over redox centers work together to generate HBrO for bromination of arenes. This work provides new insights that heterogenization of organophotocatalysts can not only help to improve their stability and recyclability, but also endow them with the ability to trigger unusual reaction mode via cooperative catalysis with supports., (© 2024. The Author(s).)

The emergence of alternative stable states in forest systems has significant implications for the functioning and structure of the terrestrial biosphere, yet empirical evidence remains scarce. Here, we combine global forest biodiversity observations and simulations to test for alternative stable states in the presence of evergreen and deciduous forest types. We reveal a bimodal distribution of forest leaf types across temperate regions of the Northern Hemisphere that cannot be explained by the environment alone, suggesting signatures of alternative forest states. Moreover, we empirically demonstrate the existence of positive feedbacks in tree growth, recruitment and mortality, with trees having 4-43% higher growth rates, 14-17% higher survival rates and 4-7 times higher recruitment rates when they are surrounded by trees of their own leaf type. Simulations show that the observed positive feedbacks are necessary and sufficient to generate alternative forest states, which also lead to dependency on history (hysteresis) during ecosystem transition from evergreen to deciduous forests and vice versa. We identify hotspots of bistable forest types in evergreen-deciduous ecotones, which are likely driven by soil-related positive feedbacks. These findings are integral to predicting the distribution of forest biomes, and aid to our understanding of biodiversity, carbon turnover, and terrestrial climate feedbacks., (© 2024. The Author(s).)

Forest carbon sequestration capacity in China remains uncertain due to underrepresented tree demographic dynamics and overlooked of harvest impacts. In this study, we employ a process-based biogeochemical model to make projections by using national forest inventories, covering approximately 415,000 permanent plots, revealing an expansion in biomass carbon stock by 13.6 ± 1.5 Pg C from 2020 to 2100, with additional sink through augmentation of wood product pool (0.6-2.0 Pg C) and spatiotemporal optimization of forest management (2.3 ± 0.03 Pg C). We find that statistical model might cause large bias in long-term projection due to underrepresentation or neglect of wood harvest and forest demographic changes. Remarkably, disregarding the repercussions of harvesting on forest age can result in a premature shift in the timing of the carbon sink peak by 1-3 decades. Our findings emphasize the pressing necessity for the swift implementation of optimal forest management strategies for carbon sequestration enhancement., (© 2024. The Author(s).)

Seawater electroreduction is attractive for future H 2 production and intermittent energy storage, which has been hindered by aggressive Mg 2+ /Ca 2+ precipitation at cathodes and consequent poor stability. Here we present a vital microscopic bubble/precipitate traffic system (MBPTS) by constructing honeycomb-type 3D cathodes for robust anti-precipitation seawater reduction (SR), which massively/uniformly release small-sized H 2 bubbles to almost every corner of the cathode to repel Mg 2+ /Ca 2+ precipitates without a break. Noticeably, the optimal cathode with built-in MBPTS not only enables state-of-the-art alkaline SR performance (1000-h stable operation at -1 A cm -2 ) but also is highly specialized in catalytically splitting natural seawater into H 2 with the greatest anti-precipitation ability. Low precipitation amounts after prolonged tests under large current densities reflect genuine efficacy by our MBPTS. Additionally, a flow-type electrolyzer based on our optimal cathode stably functions at industrially-relevant 500 mA cm -2 for 150 h in natural seawater while unwaveringly sustaining near-100% H 2 Faradic efficiency. Note that the estimated price (~1.8 US$/kg H2 ) is even cheaper than the US Department of Energy's goal price (2 US$/kg H2 )., (© 2024. The Author(s).)

The histamine H 4 receptor (H 4 R) plays key role in immune cell function and is a highly valued target for treating allergic and inflammatory diseases. However, structural information of H 4 R remains elusive. Here, we report four cryo-EM structures of H 4 R/G i complexes, with either histamine or synthetic agonists clobenpropit, VUF6884 and clozapine bound. Combined with mutagenesis, ligand binding and functional assays, the structural data reveal a distinct ligand binding mode where D94 3.32 and a π-π network determine the orientation of the positively charged group of ligands, while E182 5.46 , located at the opposite end of the ligand binding pocket, plays a key role in regulating receptor activity. The structural insight into H 4 R ligand binding allows us to identify mutants at E182 5.46 for which the agonist clobenpropit acts as an inverse agonist and to correctly predict inverse agonism of a closely related analog with nanomolar potency. Together with the findings regarding receptor activation and G i engagement, we establish a framework for understanding H 4 R signaling and provide a rational basis for designing novel antihistamines targeting H 4 R., (© 2024. The Author(s).)

Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. Here, we conduct NMR- and MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- and one-week post-operative sera and urines from 560 participants across three hospitals, with machine learning and WGCNA. Aberrations in 'alanine, aspartate and glutamate metabolism' proved to be prevalent throughout the ESCC evolution, consistently identified by NMR and MS, and reflected in 16 serum and 10 urine metabolic signatures in both discovery and validation sets. NMR-based simplified panels of any five serum or urine metabolites outperform clinical serological tumor markers (AUC = 0.984 and 0.930, respectively), and are effective in distinguishing early-stage ESCC in test set (serum accuracy = 0.994, urine accuracy = 0.879). Collectively, NMR-based biofluid screening can reveal characteristic metabolic events of ESCC and be feasible for early detection (ChiCTR2300073613)., (© 2024. The Author(s).)

Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour's metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine's conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H 2 O 2 -dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal--iron overload--through WNT/MYC signalling, as well as the subsequent elevated polyamine synthesis, thus forming a ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H 2 O 2 positive feedback loop that amplifies ferroptosis. Meanwhile, we notice that ferroptotic cells release enhanced polyamine-containing extracellular vesicles into the microenvironment, thereby further sensitizing neighbouring cells to ferroptosis and accelerating the "spread" of ferroptosis in the tumour region. Besides, polyamine supplementation also sensitizes cancer cells or xenograft tumours to radiotherapy or chemotherapy through inducing ferroptosis. Considering that cancer cells are often characterized by elevated intracellular polyamine pools, our results indicate that polyamine metabolism exposes a targetable vulnerability to ferroptosis and represents an exciting opportunity for therapeutic strategies for cancer., (© 2024. The Author(s).)

Translational control is crucial for protein production in various biological contexts. Here, we use Ribo-seq and RNA-seq to show that genes related to oxidative phosphorylation are translationally downregulated during heart regeneration. We find that Nat10 regulates the expression of Uqcr11 and Uqcrb mRNAs in mouse and human cardiomyocytes. In mice, overexpression of Nat10 in cardiomyocytes promotes cardiac regeneration and improves cardiac function after injury. Conversely, treating neonatal mice with Remodelin-a Nat10 pharmacological inhibitor-or genetically removing Nat10 from their cardiomyocytes both inhibit heart regeneration. Mechanistically, Nat10 suppresses the expression of Uqcr11 and Uqcrb independently of its ac4C enzyme activity. This suppression weakens mitochondrial respiration and enhances the glycolytic capacity of the cardiomyocytes, leading to metabolic reprogramming. We also observe that the expression of Nat10 is downregulated in the cardiomyocytes of P7 male pig hearts compared to P1 controls. The levels of Nat10 are also lower in female human failing hearts than non-failing hearts. We further identify the specific binding regions of Nat10, and validate the pro-proliferative effects of Nat10 in cardiomyocytes derived from human embryonic stem cells. Our findings indicate that Nat10 is an epigenetic regulator during heart regeneration and could potentially become a clinical target., (© 2024. The Author(s).)

Single-shot real-time femtophotography is indispensable for imaging ultrafast dynamics during their times of occurrence. Despite their advantages over conventional multi-shot approaches, existing techniques confront restricted imaging speed or degraded data quality by the deployed optoelectronic devices and face challenges in the application scope and acquisition accuracy. They are also hindered by the limitations in the acquirable information imposed by the sensing models. Here, we overcome these challenges by developing swept coded aperture real-time femtophotography (SCARF). This computational imaging modality enables all-optical ultrafast sweeping of a static coded aperture during the recording of an ultrafast event, bringing full-sequence encoding of up to 156.3 THz to every pixel on a CCD camera. We demonstrate SCARF's single-shot ultrafast imaging ability at tunable frame rates and spatial scales in both reflection and transmission modes. Using SCARF, we image ultrafast absorption in a semiconductor and ultrafast demagnetization of a metal alloy., (© 2024. The Author(s).)

The assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures through intermolecular interactions to achieve protein-like biofunction. Here, we develop a "molecular velcro"-inspired peptide and gelatin co-assembly strategy, in which amphiphilic supramolecular tripeptides are attached to the molecular chain of gelatin methacryloyl via intra-/intermolecular interactions. We perform molecular docking and dynamics simulations to demonstrate the feasibility of this strategy and reveal the advanced structural transition of the co-assembled hydrogel, which brings more ordered β-sheet content and 10-fold or more compressive strength improvement. We conduct transcriptome analysis to reveal the role of co-assembled hydrogel in promoting cell proliferation and chondrogenic differentiation. Subcutaneous implantation evaluation confirms considerably reduced inflammatory responses and immunogenicity in comparison with type I collagen. We demonstrate that bone mesenchymal stem cells-laden co-assembled hydrogel can be stably fixed in rabbit knee joint defects by photocuring, which significantly facilitates hyaline cartilage regeneration after three months. This co-assembly strategy provides an approach for developing cartilage regenerative biomaterials., (© 2024. The Author(s).)

Understanding the nature of sliding ferroelectricity is of fundamental importance for the discovery and application of two-dimensional ferroelectric materials. In this work, we investigate the phenomenon of switchable polarization in a bilayer MoS 2 with natural rhombohedral stacking, where the spontaneous polarization is coupled with excitonic effects through asymmetric interlayer coupling. Using optical spectroscopy and imaging techniques, we observe how a released domain wall switches the polarization of a large single domain. Our results highlight the importance of domain walls in the polarization switching of non-twisted rhombohedral transition metal dichalcogenides and open new opportunities for the non-volatile control of their optical response., (© 2024. The Author(s).)

Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with BRAF V600E predominantly occurring in proximal colon cancers along with increased DNA methylation phenotype. Using mouse colon organoids, here we show that proximal and distal colon stem cells have distinct transcriptional programs that regulate stemness and differentiation. We identify that the homeobox transcription factor, CDX2, which is silenced by DNA methylation in proximal colon cancers, is a key mediator of the differential transcriptional programs. Cdx2-mediated proximal colon-specific transcriptional program concurrently is tumor suppressive, and Cdx2 loss sufficiently creates permissive state for BRAF V600E -driven transformation. Human proximal colon cancers with CDX2 downregulation showed similar transcriptional program as in mouse proximal organoids with Cdx2 loss. Developmental transcription factors, such as CDX2, are thus critical in maintaining tissue-location specific transcriptional programs that create tissue-type origin specific dependencies for tumor development., (© 2024. The Author(s).)

Tuning CO 2 hydrogenation product distribution to obtain high-selectivity target products is of great significance. However, due to the imprecise regulation of chain propagation and hydrogenation reactions, the oriented synthesis of a single product is challenging. Herein, we report an approach to controlling multiple sites with graphene fence engineering that enables direct conversion of CO 2 /H 2 mixtures into different types of hydrocarbons. Fe-Co active sites on the graphene fence surface present 50.1% light olefin selectivity, while the spatial Fe-Co nanoparticles separated by graphene fences achieve liquefied petroleum gas of 43.6%. With the assistance of graphene fences, iron carbides and metallic cobalt can efficiently regulate C-C coupling and olefin secondary hydrogenation reactions to achieve product-selective switching between light olefins and liquefied petroleum gas. Furthermore, it also creates a precedent for CO 2 direct hydrogenation to liquefied petroleum gas via a Fischer-Tropsch pathway with the highest space-time yields compared to other reported composite catalysts., (© 2024. The Author(s).)

SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. Here, we screened 974 natural compounds and identified Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Using in-silico, biochemical, and genomic approaches, we provide evidence that NPC1 also binds SARS-CoV-2 spike (S) protein on the receptor-binding domain (RBD), which is blocked by Tubeimosides. Importantly, NPC1 strongly promotes productive SARS-CoV-2 entry, which we propose is due to its influence on fusion in late endosomes. The Tubeimosides' antiviral activity and NPC1 function are further confirmed by infection with SARS-CoV-2 variants of concern (VOC), SARS-CoV, and MERS-CoV. Thus, NPC1 is a critical entry co-factor for highly pathogenic human coronaviruses (HCoVs) in the late endosomes, and Tubeimosides hold promise as a new countermeasure for these HCoVs and filoviruses., (© 2024. The Author(s).)

Metal halide solid-state electrolytes have gained widespread attention due to their high ionic conductivities, wide electrochemical stability windows, and good compatibility with oxide cathode materials. The exploration of highly ionic conductive halide electrolytes is actively ongoing. Thus, understanding the relationship between composition and crystal structure can be a critical guide for designing better halide electrolytes, which still remains obscure for reliable prediction. Here we show that the cationic polarization factor, which describes the geometric and ionic conditions, is effective in predicting the stacking structure of halide electrolytes formation. By supplementing this principle with rational design and preparation of more than 10 lithium halide electrolytes with high conductivity over 10 -3  S cm -1 at 25 °C, we establish that there should be a variety of promising halide electrolytes that have yet to be discovered and developed. This methodology may enable the systematic screening of various potential halide electrolytes and demonstrate an approach to the design of halide electrolytes with superionic conductivity beyond the structure and stability predictions., (© 2024. The Author(s).)

The flexible thermoelectric technique, which can convert heat from the human body to electricity via the Seebeck effect, is expected to provide a peerless solution for the power supply of wearables. The recent discovery of ductile semiconductors has opened a new avenue for flexible thermoelectric technology, but their power factor and figure-of-merit values are still much lower than those of classic thermoelectric materials. Herein, we demonstrate the presence of morphotropic phase boundary in Ag 2 Se-Ag 2 S pseudobinary compounds. The morphotropic phase boundary can be freely tuned by adjusting the material thermal treatment processes. High-performance ductile thermoelectric materials with excellent power factor (22 μWcm -1  K -2 ) and figure-of-merit (0.61) values are realized near the morphotropic phase boundary at 300 K. These materials perform better than all existing ductile inorganic semiconductors and organic materials. Furthermore, the in-plane flexible thermoelectric device based on these high-performance thermoelectric materials demonstrates a normalized maximum power density reaching 0.26 Wm -1 under a temperature gradient of 20 K, which is at least two orders of magnitude higher than those of flexible organic thermoelectric devices. This work can greatly accelerate the development of flexible thermoelectric technology., (© 2023. The Author(s).)

The first local mpox outbreak in Guangdong Province, China occurred in June 2023. However, epidemiological data have failed to quickly identify the source and transmission of the outbreak. Here, phylogeny and molecular evolution of 10 monkeypox virus (MPXV) genome sequences from the Guangdong outbreak were characterized, revealing local silent transmissions that may have occurred in Guangdong whose mpox outbreaks suggested a molecular epidemiological correlation with Portugal and several regions of China during the same period. The lineage IIb C.1, which includes all 10 MPXV from Guangdong, shows consistent temporal continuity in both phylogenetic characteristics and unique molecular evolutionary mutation spectrum, reflected in the continuous increase of single nucleotide polymorphisms (SNPs) and shared mutations over time. Compared with the Japan MPXV, the Guangdong MPXV showed higher genomic nucleotide differences and separated 14 shared mutations from the B.1 lineage, comprising 6 non-synonymous mutations in genes linked to host regulation, virus infection, and virus life cycle. The unique mutation spectrum with temporal continuity in IIb C.1, related to apolipoprotein B mRNA-editing catalytic polypeptide-like 3, promotes rapid viral evolution and diversification. The findings contribute to understanding the ongoing mpox outbreak in China and offer insights for developing joint prevention and control strategies., (© 2023. The Author(s).)

Molecular folding regulation with environmental stimuli is critical in living and artificial molecular machine systems. Herein, we described a macrocycle, cyclo[4] (1,3-(4,6-dimethyl)benzene)[4](1,3-(4,6-dimethyl)benzene)(4-pyridine). Under 298 K, it has three stable stiff atropisomers with names as 1 (C s symmetry), 2 (C s symmetry), and 3 (C 4v symmetry). At 393 K, 1 can reversibly transform into 2, but at 473 K, it can irrevocably transform into 3. At 338 K, 3 and (PhCN) 2 PdCl 2 complex to produce the metal-organic cage 4. Only at 338 K does the combination of 1 or 2 and (PhCN) 2 PdCl 2 create a gel-like structure. Heating both gels to 473 K transforms them into 4. In addition to offering a thermally accelerated method for modifying self-assembled systems using macrocyclic building blocks, this study also has the potential to develop the nanoscale transformation material with a thermal response., (© 2023. The Author(s).)

The pathogenesis of thyroid dysgenesis (TD) is not well understood. Here, using a combination of single-cell RNA and spatial transcriptome sequencing, we identify a subgroup of NF-κB-activated thyrocytes located at the center of thyroid tissues in postnatal mice, which maintained a partially mesenchymal phenotype. These cells actively protruded out of the thyroid primordium and generated new follicles in zebrafish embryos through continuous tracing. Suppressing NF-κB signaling affected thyrocyte migration and follicle formation, leading to a TD-like phenotype in both mice and zebrafish. Interestingly, during thyroid folliculogenesis, myeloid cells played a crucial role in promoting thyrocyte migration by maintaining close contact and secreting TNF-α. We found that cebpa mutant zebrafish, in which all myeloid cells were depleted, exhibited thyrocyte migration defects. Taken together, our results suggest that myeloid-derived TNF-α-induced NF-κB activation plays a critical role in promoting the migration of vertebrate thyrocytes for follicle generation., (© 2023. The Author(s).)

Quantum matter interacting with gauge fields, an outstanding paradigm in modern physics, underlies the description of various physical systems. Engineering artificial gauge fields in ultracold atoms offers a highly controllable access to the exotic many-body phenomena in these systems, and has stimulated intense interest. Here we implement a triangular flux ladder in the momentum space of ultracold 133 Cs atoms, and study the chiral dynamics under tunable interactions. Through measurements of the site-resolved density evolutions, we reveal how the competition between interaction and flux in the frustrated triangular geometry gives rise to flux-dependent localization and biased chiral dynamics. For the latter in particular, the symmetry between the two legs is dynamically broken, which can be attributed to frustration. We then characterize typical dynamic patterns using complementary observables. Our work opens the avenue toward exploring correlated transport in frustrated geometries, where the interplay between interactions and gauge fields plays a key role., (© 2023. The Author(s).)

While the prognostic role of immunoglobulin heavy chain locus (IGH) rearrangement in minimal residual disease (MRD) in pediatric B-acute lymphoblastic leukemia (B-ALL) has been reported, the contribution of light chain loci (IGK/IGL) remains elusive. This study is to evaluate the prognosis of IGH and IGK/IGL rearrangement-based MRD detected by next-generation sequencing in B-ALL at the end of induction (EOI) and end of consolidation (EOC). IGK/IGL rearrangements identify 5.5% of patients without trackable IGH clones. Concordance rates for IGH and IGK/IGL are 79.9% (cutoff 0.01%) at EOI and 81.0% (cutoff 0.0001%) at EOC, respectively. Patients with NGS-MRD < 0.01% at EOI or <0.0001% at EOC present excellent outcome, with 3-year event-free survival rates higher than 95%. IGH-MRD is prognostic at EOI/EOC, while IGK-MRD at EOI/EOC and IGL-MRD at EOI are not. At EOI, NGS identifies 26.2% of higher risk patients whose MRD < 0.01% by flow cytometry. However, analyzing IGK/IGL along with IGH fails to identify additional higher risk patients both at EOI and at EOC. In conclusion, IGH is crucial for MRD monitoring while IGK and IGL have relatively limited value., (© 2023. The Author(s).)