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Controlling the morphology of Pt-based nanostructures can provide a great opportunity to boost their catalytic activity and durability. Here the authors report anisotropic mesoporous Pt@Pt-skin Pt3Ni core-shell framework nanowires for oxygen reduction reaction with enhanced mass activity and stability.

Electrocatalytic reduction of CO2 into multi-carbon alcohols of high economic merit offers an effective means to close the carbon cycle. Here the authors show the synergy between inorganic and organic phases derived from rationally designed molecular precursors to produce alcohols in high efficiency.

Metal-organic frameworks are promising catalysts for CO2 electroreduction, yet limited by their poor conductivity and stability. Here, Au nanoneedles are inserted into the metalloporphyrin framework to activate C-C coupling and stabilize the structure for much enhanced ethylene production.

The substrate-catalyst interaction plays a critical role in steering the pathway of electrochemical CO2 reduction. Here the authors show the crystalline states of copper in reconstructed metal-organic frameworks were induced and stabilized by Ketjen Black conducting support, promoting C2H4 production.

Direct methanol fuel cells are promising for clean, sustainable energy, but catalysts should be optimized. Here the authors construct ultrathin nanoframes with rich crystalline defects to increase electrocatalytic activity of gold for methanol oxidation, which is surprisingly promoted by carbon monoxide.

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV 1 ] to forced vital capacity ratio <0.70 and an FEV 1  ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV 1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV 1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604., (© 2024. The Author(s).)

In the healing process of myocardial infarction, cardiac fibroblasts are activated to produce collagen, leading to adverse remodeling and heart failure. Our previous study showed that ASPP1 promotes cardiomyocyte apoptosis by enhancing the nuclear trafficking of p53. We thus explored the influence of ASPP1 on myocardial fibrosis and the underlying mechanisms. Here, we observed that ASPP1 was increased after 4 weeks of MI. Both global and myofibroblast knockout of ASPP1 in mice mitigated cardiac dysfunction and fibrosis after MI. Strikingly, ASPP1 produced the opposite influence on p53 level and cell fate in cardiac fibroblasts and cardiomyocytes. Knockdown of ASPP1 increased p53 levels and inhibited the activity of cardiac fibroblasts. ASPP1 accumulated in the cytoplasm of fibroblasts while the level of p53 was reduced following TGF-β1 stimulation; however, inhibition of ASPP1 increased the p53 level and promoted p53 nuclear translocation. Mechanistically, ASPP1 is directly bound to deubiquitinase OTUB1, thereby promoting the ubiquitination and degradation of p53, attenuating myofibroblast activity and cardiac fibrosis, and improving heart function after MI., (© 2024. The Author(s).)

High-order diffraction (HOD) from optical microstructures is undesirable in many applications because of the accompanying ghosting patterns and loss of efficiency. In contrast to suppressing HOD with subwavelength structures that challenge the fabrication of large-scale devices, managing HOD is less developed due to the lack of an efficient method for independently manipulating HOD. Here, we report independent manipulation of HODs, which are unexploited for subdiffraction-limit focusing in diffractive lenses, through an analytical formula that correlates the diffraction order and the width of each zone. The large spatial frequencies offered by the HODs enable our lenses to reduce the lateral focal size down to 0.44 λ even without any subwavelength feature (indispensable in most high-NA diffractive lenses), facilitating large-scale manufacture. Experimentally, we demonstrate high-order lens-based confocal imaging with a center-to-center dry resolution of 190 nm, the highest among visible-light confocal microscopies, and laser-ablation lithography with achieved direct-writing resolution of 400 nm (0.385 λ)., (© 2024. The Author(s).)

Type I CRISPR-Cas systems are widespread and have exhibited high versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems, with a total gene size smaller than that of SpCas9, can be developed for transcriptional activation in human cells. The efficiency of the engineered I-F2 tool can match or surpass that of dCas9. Additionally, we create a base editor using the I-F2 Cascade, which induces a considerably wide editing window (~30 nt) with a bimodal distribution. It can expand targetable sites, which is useful for disrupting functional sequences and genetic screening. This research underscores the application of compact type I systems in eukaryotes, particularly in the development of a base editor with a wide editing window., (© 2024. The Author(s).)

Harvesting electricity from ubiquitous water vapor represents a promising route to alleviate the energy crisis. However, existing studies rarely comprehensively consider the impact of natural environmental fluctuations on electrical output. Here, we demonstrate a bilayer polymer enabling self-sustaining and highly efficient moisture-electric generation from the hydrological cycle by establishing a stable internal directed water/ion flow through thermal exchange with the ambient environment. Specifically, the radiative cooling effect of the hydrophobic top layer prevents the excessive daytime evaporation from solar absorption while accelerating nighttime moisture sorption. The introduction of LiCl into the bottom hygroscopic ionic hydrogel enhances moisture sorption capacity and facilitates ion transport, thus ensuring efficient energy conversion. A single device unit (1 cm 2 ) can continuously generate a voltage of ~0.88 V and a current of ~306 μA, delivering a maximum power density of ~51 μW cm -2 at 25 °C and 70% relative humidity (RH). The device has been demonstrated to operate steadily outdoors for continuous 6 days., (© 2024. The Author(s).)

In many cancers, a stem-like cell subpopulation mediates tumor initiation, dissemination and drug resistance. Here, we report that cancer stem cell (CSC) abundance is transcriptionally regulated by C-terminally phosphorylated p27 (p27pT157pT198). Mechanistically, this arises through p27 co-recruitment with STAT3/CBP to gene regulators of CSC self-renewal including MYC, the Notch ligand JAG1, and ANGPTL4. p27pTpT/STAT3 also recruits a SIN3A/HDAC1 complex to co-repress the Pyk2 inhibitor, PTPN12. Pyk2, in turn, activates STAT3, creating a feed-forward loop increasing stem-like properties in vitro and tumor-initiating stem cells in vivo. The p27-activated gene profile is over-represented in STAT3 activated human breast cancers. Furthermore, mammary transgenic expression of phosphomimetic, cyclin-CDK-binding defective p27 (p27CK-DD) increases mammary duct branching morphogenesis, yielding hyperplasia and microinvasive cancers that can metastasize to liver, further supporting a role for p27pTpT in CSC expansion. Thus, p27pTpT interacts with STAT3, driving transcriptional programs governing stem cell expansion or maintenance in normal and cancer tissues., (© 2024. The Author(s).)

Type II topoisomerases are ubiquitous enzymes that play a pivotal role in modulating the topological configuration of double-stranded DNA. These topoisomerases are required for DNA metabolism and have been extensively studied in both prokaryotic and eukaryotic organisms. However, our understanding of virus-encoded type II topoisomerases remains limited. One intriguing example is the African swine fever virus, which stands as the sole mammalian-infecting virus encoding a type II topoisomerase. In this work, we use several approaches including cryo-EM, X-ray crystallography, and biochemical assays to investigate the structure and function of the African swine fever virus type II topoisomerase, pP1192R. We determine the structures of pP1192R in different conformational states and confirm its enzymatic activity in vitro. Collectively, our results illustrate the basic mechanisms of viral type II topoisomerases, increasing our understanding of these enzymes and presenting a potential avenue for intervention strategies to mitigate the impact of the African swine fever virus., (© 2024. The Author(s).)

Caustics occur in diverse physical systems, spanning the nano-scale in electron microscopy to astronomical-scale in gravitational lensing. As envelopes of rays, optical caustics result in sharp edges or extended networks. Caustics in structured light, characterized by complex-amplitude distributions, have innovated numerous applications including particle manipulation, high-resolution imaging techniques, and optical communication. However, these applications have encountered limitations due to a major challenge in engineering caustic fields with customizable propagation trajectories and in-plane intensity profiles. Here, we introduce the "compensation phase" via 3D-printed metasurfaces to shape caustic fields with curved trajectories in free space. The in-plane caustic patterns can be preserved or morphed from one structure to another during propagation. Large-scale fabrication of these metasurfaces is enabled by the fast-prototyping and cost-effective two-photon polymerization lithography. Our optical elements with the ultra-thin profile and sub-millimeter extension offer a compact solution to generating caustic structured light for beam shaping, high-resolution microscopy, and light-matter-interaction studies., (© 2024. The Author(s).)

Terrestrial self-reconfigurable robot swarms offer adaptable solutions for various tasks. However, most existing swarms are limited to controlled indoor settings, and often compromise stability due to their freeform connections. To address these issues, we present a snail robotic swarm system inspired by land snails, tailored for unstructured environments. Our system also employs a two-mode connection mechanism, drawing from the adhesive capabilities of land snails. The free mode, mirroring a snail's natural locomotion, leverages magnet-embedded tracks for freeform mobility, thereby enhancing adaptability and efficiency. The strong mode, analogous to a snail's response to disturbance, employs a vacuum sucker with directional polymer stalks for robust adhesion. By assigning specific functions to each mode, our system achieves a balance between mobility and secure connections. Outdoor experiments demonstrate the capabilities of individual robots and the exceptional synergy within the swarm. This research advances the real-world applications of terrestrial robotic swarms in unstructured environments., (© 2024. The Author(s).)

The root-associated microbiota plays an important role in the response to environmental stress. However, the underlying mechanisms controlling the interaction between salt-stressed plants and microbiota are poorly understood. Here, by focusing on a salt-tolerant plant wild soybean (Glycine soja), we demonstrate that highly conserved microbes dominated by Pseudomonas are enriched in the root and rhizosphere microbiota of salt-stressed plant. Two corresponding Pseudomonas isolates are confirmed to enhance the salt tolerance of wild soybean. Shotgun metagenomic and metatranscriptomic sequencing reveal that motility-associated genes, mainly chemotaxis and flagellar assembly, are significantly enriched and expressed in salt-treated samples. We further find that roots of salt stressed plants secreted purines, especially xanthine, which induce motility of the Pseudomonas isolates. Moreover, exogenous application for xanthine to non-stressed plants results in Pseudomonas enrichment, reproducing the microbiota shift in salt-stressed root. Finally, Pseudomonas mutant analysis shows that the motility related gene cheW is required for chemotaxis toward xanthine and for enhancing plant salt tolerance. Our study proposes that wild soybean recruits beneficial Pseudomonas species by exudating key metabolites (i.e., purine) against salt stress., (© 2024. The Author(s).)

One-unit-cell FeSe films on SrTiO 3 substrates are of great interest owing to significantly enlarged pairing gaps characterized by two coherence peaks at ±10 meV and ±20 meV. In-situ transport measurement is desired to reveal novel properties. Here, we performed in-situ microscale electrical transport and combined scanning tunneling microscopy measurements on continuous one-unit-cell FeSe films with twin boundaries. We observed two spatially coexisting superconducting phases in domains and on boundaries, characterized by distinct superconducting gaps ( Δ 1 ~15 meV vs. Δ 2 ~10 meV) and pairing temperatures (T p1 ~52.0 K vs. T p2 ~37.3 K), and correspondingly two-step nonlinear V ~ I α behavior but a concurrent Berezinskii-Kosterlitz-Thouless (BKT)-like transition occurring at T BKT ~28.7 K. Moreover, the onset transition temperature T c onset ~54 K and zero-resistivity temperature T c zero ~31 K are consistent with T p1 and T BKT , respectively. Our results indicate the broadened superconducting transition in FeSe/SrTiO 3 is related to intrinsic electronic inhomogeneity due to distinct two-gap features and phase fluctuations of two-dimensional superconductivity., (© 2024. The Author(s).)

Low-dimensional/three-dimensional perovskite heterojunctions have shown great potential for improving the performance of perovskite photovoltaics, but large organic cations in low-dimensional perovskites hinder charge transport and cause carrier mobility anisotropy at the heterojunction interface. Here, we report a low-dimensional/three-dimensional perovskite heterojunction that introduces strong aromatic conjugated low-dimensional perovskites in p-i-n devices to reduce the electron transport resistance crossing the perovskite/electron extraction interface. The strong aromatic conjugated π-conjugated network results in continuous energy orbits among [Pb 2 I 6 ] 2- frameworks, thereby effectively suppressing interfacial non-radiative recombination and boosting carrier extraction. Consequently, the devices achieved an improved efficiency to 25.66% (certified 25.20%), and maintained over 95% of the initial efficiency after 1200 hours and 1000 hours under ISOS-L-1I and ISOS-D-1 protocols, respectively. The chemical design of strong aromatic conjugated molecules in perovskite heterojunctions provides a promising avenue for developing efficient and stable perovskite photovoltaics., (© 2024. The Author(s).)

The rational design of efficient bifunctional single-atom electrocatalysts for industrial water splitting and the comprehensive understanding of its complex catalytic mechanisms remain challenging. Here, we report a Ni single atoms supported on oxygen-incorporated Mo 2 C via Ni-O-Mo bridge bonds, that gives high oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) bifunctional activity. By ex situ synchrotron X-ray absorption spectroscopy and electron microscopy, we found that after HER, the coordination number and bond lengths of Ni-O and Ni-Mo (Ni-O-Mo) were all altered, yet the Ni species still remain atomically dispersed. In contrast, after OER, the atomically dispersed Ni were agglomerated into very small clusters with new Ni-Ni (Ni-O-Ni) bonds appeared. Combining experimental results and DFT calculations, we infer the oxidation degree of Mo 2 C and the configuration of single-atom Ni are both vital for HER or OER. This study provides both a feasible strategy and model to rational design highly efficient electrocatalysts for water electrolysis., (© 2024. The Author(s).)

The current challenge of wearable/implantable personal dosimeters for medical diagnosis and radiotherapy applications is lack of suitable detector materials possessing both excellent detection performance and biocompatibility. Here, we report a solution-grown biocompatible organic single crystalline semiconductor (OSCS), 4-Hydroxyphenylacetic acid (4HPA), achieving real-time spectral detection of charged particles with single-particle sensitivity. Along in-plane direction, two-dimensional anisotropic 4HPA exhibits a large electron drift velocity of 5 × 10 5  cm s -1 at "radiation-mode" while maintaining a high resistivity of (1.28 ± 0.003) × 10 12 Ω·cm at "dark-mode" due to influence of dense π-π overlaps and high-energy L1 level. Therefore, 4HPA detectors exhibit the record spectra detection of charged particles among their organic counterparts, with energy resolution of 36%, (μt) e of (4.91 ± 0.07) × 10 -5  cm 2  V -1 , and detection time down to 3 ms. These detectors also show high X-ray detection sensitivity of 16,612 μC Gy abs -1  cm -3 , detection of limit of 20 nGy air s -1 , and long-term stability after 690 Gy air irradiation., (© 2024. The Author(s).)

Keen desires for artificial mimicry of biological polymers and property improvement of synthesized ones have triggered intensive explorations for sequence-controlled copolymerization. However, conventional synthesis faces great challenges to achieve this goal due to the strict requirements on reaction kinetics of comonomer pairs and tedious synthetic processes. Here, sequence-controlled alternating copolymerization with molecular precision is realized on surface. The stoichiometric control serves as a thermodynamic strategy to steer the polymerization selectivity, which enables the selective alternating organometallic copolymerization via intermolecular metalation of 4,4"-dibromo-p-terphenyl (P-Br) and 2,5-diethynyl-1,4-bis(phenylethynyl)benzene (A-H) with Ag adatoms on Ag(111) at P-Br: A-H = 2, as verified by scanning tunneling microscopy and density functional theory studies. In contrast, homopolymerization yield increases as the stoichiometric ratio deviates from 2. The microscopic characterizations rationalize the mechanism, providing a delicate explanation of the stoichiometry-dependent polymerization. These findings pave a way to actualizing an efficient sequence control of copolymerization by surface chemistry., (© 2024. The Author(s).)

Defined traffic laws must be respected by all vehicles when driving on the road, including self-driving vehicles without human drivers. Nevertheless, the ambiguity of human-oriented traffic laws, particularly compliance thresholds, poses a significant challenge to the implementation of regulations on self-driving vehicles, especially in detecting illegal driving behaviors. To address these challenges, here we present a trigger-based hierarchical online monitor for self-assessment of driving behavior, which aims to improve the rationality and real-time performance of the monitoring results. Furthermore, the general principle to determine the ambiguous compliance threshold based on real driving behaviors is proposed, and the specific outcomes and sensitivity of the compliance threshold selection are analyzed. In this work, the effectiveness and real-time capability of the online monitor were verified using both Chinese human driving behavior datasets and real vehicle field tests, indicating the potential for implementing regulations in self-driving vehicles for online monitoring., (© 2024. The Author(s).)

Invariant cell lineage in C. elegans enables spatiotemporal resolution of transcriptional regulatory mechanisms controlling the fate of each cell. Here, we develop RAPCAT (Robust-point-matching- And Piecewise-affine-based Cell Annotation Tool) to automate cell identity assignment in three-dimensional image stacks of L1 larvae and profile reporter expression of 620 transcription factors in every cell. Transcription factor profile-based clustering analysis defines 80 cell types distinct from conventional phenotypic cell types and identifies three general phenotypic modalities related to these classifications. First, transcription factors are broadly downregulated in quiescent stage Hermaphrodite Specific Neurons, suggesting stage- and cell type-specific variation in transcriptome size. Second, transcription factor expression is more closely associated with morphology than other phenotypic modalities in different pre- and post-differentiation developmental stages. Finally, embryonic cell lineages can be associated with specific transcription factor expression patterns and functions that persist throughout postembryonic life. This study presents a comprehensive transcription factor atlas for investigation of intra-cell type heterogeneity., (© 2024. The Author(s).)

Materials showing second-order nonlinear transport under time reversal symmetry can be used for Radio Frequency (RF) rectification, but practical application demands room temperature operation and sensitivity to microwatts level RF signals in the ambient. In this study, we demonstrate that BiTeBr exhibits a giant nonlinear response which persists up to 350 K. Through scaling and symmetry analysis, we show that skew scattering is the dominant mechanism. Additionally, the sign of the nonlinear response can be electrically switched by tuning the Fermi energy. Theoretical analysis suggests that the large Rashba spin-orbit interactions (SOI), which gives rise to the chirality of the Bloch electrons, provide the microscopic origin of the observed nonlinear response. Our BiTeBr rectifier is capable of rectifying radiation within the frequency range of 0.2 to 6 gigahertz at room temperature, even at extremely low power levels of -15 dBm, and without the need for external biasing. Our work highlights that materials exhibiting large Rashba SOI have the potential to exhibit nonlinear responses at room temperature, making them promising candidates for harvesting high-frequency and low-power ambient electromagnetic energy., (© 2024. The Author(s).)

Single-cell technologies enable the dynamic analyses of cell fate mapping. However, capturing the gene regulatory relationships and identifying the driver factors that control cell fate decisions are still challenging. We present CEFCON, a network-based framework that first uses a graph neural network with attention mechanism to infer a cell-lineage-specific gene regulatory network (GRN) from single-cell RNA-sequencing data, and then models cell fate dynamics through network control theory to identify driver regulators and the associated gene modules, revealing their critical biological processes related to cell states. Extensive benchmarking tests consistently demonstrated the superiority of CEFCON in GRN construction, driver regulator identification, and gene module identification over baseline methods. When applied to the mouse hematopoietic stem cell differentiation data, CEFCON successfully identified driver regulators for three developmental lineages, which offered useful insights into their differentiation from a network control perspective. Overall, CEFCON provides a valuable tool for studying the underlying mechanisms of cell fate decisions from single-cell RNA-seq data., (© 2023. The Author(s).)

One-dimensional (1D) nanomaterials have sparked widespread research interest owing to their fascinating physicochemical properties, however, the direct self-assembly of 1D porous nanomaterials and control over their porosity still presents a grand challenge. Herein, we report a monomicelle oriented self-assembly approach to fabricate 1D mesoporous nanostructures with uniform diameter, high aspect ratio and ordered mesostructure. This strategy features the introduction of hexamethylenetetramine as a curing agent, which can subtly control the monomicelle self-assembly kinetics, thus enabling formation of high-quality 1D ordered mesostructures. Meanwhile, the micellar structure can be precisely manipulated by changing the reactant stoichiometric ratio, resulting in tailorable mesophases from 3D cubic (Im-3m) to 2D hexagonal (p6mm) symmetries. More interestingly, the resultant mesoporous nanofibers can be assembled into 3D hierarchical cryogels on a large scale. The 1D nanoscale of the mesoporous nanofibers, in combination with small diameter (~65 nm), high aspect ratio (~154), large surface area (~452 m 2 g -1 ), and 3D open mesopores (~6 nm), endows them with excellent performances for sodium ion storage and water purification. Our methodology opens up an exciting way to develop next-generation ordered mesoporous materials for various applications., (© 2023. The Author(s).)

Post-surgical treatments of the human throat often require continuous monitoring of diverse vital and muscle activities. However, wireless, continuous monitoring and analysis of these activities directly from the throat skin have not been developed. Here, we report the design and validation of a fully integrated standalone stretchable device platform that provides wireless measurements and machine learning-based analysis of diverse vibrations and muscle electrical activities from the throat. We demonstrate that the modified composite hydrogel with low contact impedance and reduced adhesion provides high-quality long-term monitoring of local muscle electrical signals. We show that the integrated triaxial broad-band accelerometer also measures large body movements and subtle physiological activities/vibrations. We find that the combined data processed by a 2D-like sequential feature extractor with fully connected neurons facilitates the classification of various motion/speech features at a high accuracy of over 90%, which adapts to the data with noise from motion artifacts or the data from new human subjects. The resulting standalone stretchable device with wireless monitoring and machine learning-based processing capabilities paves the way to design and apply wearable skin-interfaced systems for the remote monitoring and treatment evaluation of various diseases., (© 2023. The Author(s).)

Learning effective molecular feature representation to facilitate molecular property prediction is of great significance for drug discovery. Recently, there has been a surge of interest in pre-training graph neural networks (GNNs) via self-supervised learning techniques to overcome the challenge of data scarcity in molecular property prediction. However, current self-supervised learning-based methods suffer from two main obstacles: the lack of a well-defined self-supervised learning strategy and the limited capacity of GNNs. Here, we propose Knowledge-guided Pre-training of Graph Transformer (KPGT), a self-supervised learning framework to alleviate the aforementioned issues and provide generalizable and robust molecular representations. The KPGT framework integrates a graph transformer specifically designed for molecular graphs and a knowledge-guided pre-training strategy, to fully capture both structural and semantic knowledge of molecules. Through extensive computational tests on 63 datasets, KPGT exhibits superior performance in predicting molecular properties across various domains. Moreover, the practical applicability of KPGT in drug discovery has been validated by identifying potential inhibitors of two antitumor targets: hematopoietic progenitor kinase 1 (HPK1) and fibroblast growth factor receptor 1 (FGFR1). Overall, KPGT can provide a powerful and useful tool for advancing the artificial intelligence (AI)-aided drug discovery process., (© 2023. The Author(s).)

Rheumatoid arthritis (RA) involves several classes of pathogenic autoantibodies, some of which react with type-II collagen (COL2) in articular cartilage. We previously described a subset of COL2 antibodies targeting the F4 epitope (ERGLKGHRGFT) that could be regulatory. Here, using phage display, we developed recombinant antibodies against this epitope and examined the underlying mechanism of action. One of these antibodies, R69-4, protected against cartilage antibody- and collagen-induced arthritis in mice, but not autoimmune disease models independent of arthritogenic autoantibodies. R69-4 was further shown to cross-react with a large range of proteins within the inflamed synovial fluid, such as the complement protein C1q. Complexed R69-4 inhibited neutrophil FCGR3 signaling, thereby impairing downstream IL-1β secretion and neutrophil self-orchestrated recruitment. Likewise, human isotypes of R69-4 protected against arthritis with comparable efficiency. We conclude that R69-4 abrogates autoantibody-mediated arthritis mainly by hindering FCGR3 signaling, highlighting its potential clinical utility in acute RA., (© 2023. Springer Nature Limited.)

Planar diffractive lenses (PDLs) with optimized but disordered structures can focus light beyond the diffraction limit. However, these disordered structures have inevitably destroyed wide-field imaging capability, limiting their applications in microscopy. Here, we introduce information entropy S to evaluate the disorder of an objective chip by using the probability of its structural deviation from standard Fresnel zone plates. Inspired by the theory of entropy change, we predict an equilibrium point [Formula: see text] to balance wide-field imaging (theoretically evaluated by the Strehl ratio) and subdiffraction-limit focusing. To verify this, a [Formula: see text] objective chip with a record-long focal length of 1 mm is designed with [Formula: see text], which is the nearest to the equilibrium point among all reported PDLs. Consequently, our fabricated chip can focus light with subdiffraction-limit size of 0.44 λ and image fine details with spatial frequencies up to 4000 lp/mm experimentally. These unprecedented performances enable ultracompact reflective confocal microscopy for superresolution imaging., (© 2023. Springer Nature Limited.)

The mechanisms underlying the transformation of chronic myeloid leukemia (CML) from chronic phase (CP) to blast crisis (BC) are not fully elucidated. Here, we show lower levels of miR-142 in CD34 + CD38 - blasts from BC CML patients than in those from CP CML patients, suggesting that miR-142 deficit is implicated in BC evolution. Thus, we create miR-142 knockout CML (i.e., miR-142 -/- BCR-ABL) mice, which develop BC and die sooner than miR-142 wt CML (i.e., miR-142 +/+ BCR-ABL) mice, which instead remain in CP CML. Leukemic stem cells (LSCs) from miR-142 -/- BCR-ABL mice recapitulate the BC phenotype in congenic recipients, supporting LSC transformation by miR-142 deficit. State-transition and mutual information analyses of "bulk" and single cell RNA-seq data, metabolomic profiling and functional metabolic assays identify enhanced fatty acid β-oxidation, oxidative phosphorylation and mitochondrial fusion in LSCs as key steps in miR-142-driven BC evolution. A synthetic CpG-miR-142 mimic oligodeoxynucleotide rescues the BC phenotype in miR-142 -/- BCR-ABL mice and patient-derived xenografts., (© 2023. Springer Nature Limited.)

Base editing technology is an ideal solution for treating pathogenic single-nucleotide variations (SNVs). No gene editing therapy has yet been approved for eye diseases, such as retinitis pigmentosa (RP). Here, we show, in the rd10 mouse model, which carries an SNV identified as an RP-causing mutation in human patients, that subretinal delivery of an optimized dual adeno-associated virus system containing the adenine base editor corrects the pathogenic SNV in the neuroretina with up to 49% efficiency. Light microscopy showed that a thick and robust outer nuclear layer (photoreceptors) was preserved in the treated area compared with the thin, degenerated outer nuclear layer without treatment. Substantial electroretinogram signals were detected in treated rd10 eyes, whereas control treated eyes showed minimal signals. The water maze experiment showed that the treatment substantially improved vision-guided behavior. Together, we construct and validate a translational therapeutic solution for the treatment of RP in humans. Our findings might accelerate the development of base-editing based gene therapies., (© 2023. Springer Nature Limited.)

Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing of tolerogenic dendritic cells, we identified N-myc downregulated gene 2 (Ndrg2), which marks a specific population of dendritic cell progenitors, as a promising target for CRISPR knockout. Ndrg2-knockout alters the transcriptomic profile of dendritic cells and preserves an immature cell state with a strong pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a therapeutic hydrogel for in vivo cell delivery and developed an effective translational approach for dendritic cell-based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in dendritic cells for treating various types of chronic wounds., (© 2023. Springer Nature Limited.)

Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment., (© 2023. The Author(s).)

The construction of mesoporous Janus nanoparticles (mJNPs) with controllable components is of great significance for the development of sophisticated nanomaterials with synergistically enhanced functionalities and applications. However, the compositions of reported mJNPs are mainly the functionally inert SiO 2 and polymers. The universal synthesis of metal-compound based mJNPs with abundant functionalities is urgently desired, but remains a substantial challenge. Herein, we present a hydrophilicity mediated interfacial selective assembly strategy for the versatile synthesis of metal-compound based mJNPs. Starting from the developed silica-based mJNPs with anisotropic dual-surface of hydrophilic SiO 2 and hydrophobic organosilica, metal precursor can selectively deposit onto the hydrophilic SiO 2 subunit to form the metal-compound based mJNPs. This method shows good universality and can be used for the synthesis of more than 20 kinds of metal-compound based mJNPs, including alkali-earth metal compounds, transition metal compounds, rare-earth metal compounds etc. Besides, the composition of the metal-compound subunit can be well tuned from single to multiple metal elements, even high-entropy complexes. We believe that the synthesis method and obtained new members of mJNPs provide a very broad platform for the construction and application of mJNPs with rational designed functions and structures., (© 2023. The Author(s).)

The interactions between adsorbed gas molecules within porous metal-organic frameworks are crucial to gas selectivity but remain poorly explored. Here, we report the modulation of packing geometries of CO 2 and C 2 H 2 clusters within the ultramicroporous CUK-1 material as a function of temperature. In-situ synchrotron X-ray diffraction reveals a unique temperature-dependent reversal of CO 2 and C 2 H 2 adsorption affinities on CUK-1, which is validated by gas sorption and dynamic breakthrough experiments, affording high-purity C 2 H 2 (99.95%) from the equimolar mixture of C 2 H 2 /CO 2 via a one-step purification process. At low temperatures (<253 K), CUK-1 preferentially adsorbs CO 2 with both high selectivity (>10) and capacity (170 cm 3 g -1 ) owing to the formation of CO 2 tetramers that simultaneously maximize the guest-guest and host-guest interactions. At room temperature, conventionally selective adsorption of C 2 H 2 is observed. The selectivity reversal, structural robustness, and facile regeneration of CUK-1 suggest its potential for producing high-purity C 2 H 2 by temperature-swing sorption., (© 2023. The Author(s).)

Electrochemical CO 2 conversion to methane, powered by intermittent renewable electricity, provides an entrancing opportunity to both store renewable electric energy and utilize emitted CO 2 . Copper-based single atom catalysts are promising candidates to restrain C-C coupling, suggesting feasibility in further protonation of CO* to CHO* for methane production. In theoretical studies herein, we find that introducing boron atoms into the first coordination layer of Cu-N 4 motif facilitates the binding of CO* and CHO* intermediates, which favors the generation of methane. Accordingly, we employ a co-doping strategy to fabricate B-doped Cu-N x atomic configuration (Cu-N x B y ), where Cu-N 2 B 2 is resolved to be the dominant site. Compared with Cu-N 4 motifs, as-synthesized B-doped Cu-N x structure exhibits a superior performance towards methane production, showing a peak methane Faradaic efficiency of 73% at -1.46 V vs. RHE and a maximum methane partial current density of -462 mA cm -2 at -1.94 V vs. RHE. Extensional calculations utilizing two-dimensional reaction phase diagram analysis together with barrier calculation help to gain more insights into the reaction mechanism of Cu-N 2 B 2 coordination structure., (© 2023. The Author(s).)

Transition-metal-catalyzed allylic substitution reactions (Tsuji-Trost reactions) proceeding via a π-allyl metal intermediate have been demonstrated as a powerful tool in synthetic chemistry. Herein, we disclose an unprecedented π-allyl metal species migration, walking on the carbon chain involving 1,4-hydride shift as confirmed by deuterium labeling experiments. This migratory allylic arylation can be realized under dual catalysis of nickel and lanthanide triflate, a Lewis acid. Olefin migration has been observed to preferentially occur with the substrate of 1,n-enols (n ≥ 3). The robust nature of the allylic substitution strategy is reflected by a broad scope of substrates with the control of regio- and stereoselectivity. DFT studies suggest that π-allyl metal species migration consists of the sequential β-H elimination and migratory insertion, with diene not being allowed to release from the metal center before producing a new π-allyl nickel species., (© 2023. The Author(s).)

The near-trench coseismic rupture behaviour of the 2011 Tohoku-Oki earthquake remains poorly understood due to the scarcity of near-field observations. Differential bathymetry offers a unique approach to studying offshore coseismic seafloor deformation but has a limited horizontal resolution. Here we use differential bathymetry estimates with improved horizontal resolutions to investigate near-trench coseismic slip behaviours in the 2011 Tohoku-Oki earthquake. In the main rupture region, a velocity-strengthening behaviour in the shallow fault is observed. By contrast, the seafloor uplift decreases towards the trench, but the trend inverts near the backstop interface outcrop, revealing significant off-fault deformation features. Amongst various competing off-fault effects observed, we suggest that inelastic deformation plays a predominant role in near-trench tsunami excitation. Large trench-bleaching rupture is also observed immediately north of 39°, delimiting the northern extent of the main rupture region. Overall, striking spatial heterogeneity of the shallow rupture behaviour is revealed for the region., (© 2023. The Author(s).)

Although battery electric vehicles (BEVs) are climate-friendly alternatives to internal combustion engine vehicles (ICEVs), an important but often ignored fact is that the climate mitigation benefits of BEVs are usually delayed. The manufacture of BEVs is more carbon-intensive than that of ICEVs, leaving a greenhouse gas (GHG) debt to be paid back in the future use phase. Here we analyze millions of vehicle data from the Chinese market and show that the GHG break-even time (GBET) of China's BEVs ranges from zero (i.e., the production year) to over 11 years, with an average of 4.5 years. 8% of China's BEVs produced and sold between 2016 and 2018 cannot pay back their GHG debt within the eight-year battery warranty. We suggest enhancing the share of BEVs reaching the GBET by promoting the effective substitution of BEVs for ICEVs instead of the single-minded pursuit of speeding up the BEV deployment race., (© 2023. The Author(s).)

African swine fever virus (ASFV) poses a great threat to the global pig industry and food security. Currently, 24 ASFV genotypes have been reported but it is unclear whether recombination of different genotype viruses occurs in nature. In this study, we detect three recombinants of genotype I and II ASFVs in pigs in China. These recombinants are genetically similar and classified as genotype I according to their B646L gene, yet 10 discrete fragments accounting for over 56% of their genomes are derived from genotype II virus. Animal studies with one of the recombinant viruses indicate high lethality and transmissibility in pigs, and deletion of the virulence-related genes MGF&#95;505/360 and EP402R derived from virulent genotype II virus highly attenuates its virulence. The live attenuated vaccine derived from genotype II ASFV is not protective against challenge of the recombinant virus. These naturally occurring recombinants of genotype I and II ASFVs have the potential to pose a challenge to the global pig industry., (© 2023. The Author(s).)

Transition metal-based homogeneous photocatalysts offer a wealth of opportunities for organic synthesis. The most versatile ruthenium(II) and iridium(III) polypyridyl complexes, however, are among the rarest metal complexes. Moreover, immobilizing these precious catalysts for recycling is challenging as their opacity may obstruct light transmission. Recovery of homogeneous catalysts by conventional polymeric membranes is promising but limited, as the modulation of their pore structure and tolerance of polar organic solvents are challenging. Here, we report the effective recovery of homogeneous photocatalysts using covalent organic framework (COF) membranes. An array of COF membranes with tunable pore sizes and superior organic solvent resistance were prepared. Ruthenium and iridium photoredox catalysts were recycled for 10 cycles in various types of photochemical reactions, constantly achieving high catalytical performance, high recovery rates, and high permeance. We successfully recovered the photocatalysts at gram-scale. Furthermore, we demonstrated a cascade isolation of an iridium photocatalyst and purification of a small organic molecule product with COF membranes possessing different pore sizes. Our results indicate an intriguing potential to shift the paradigm of the pharmaceutical and fine chemical synthesis campaign., (© 2023. The Author(s).)

A comprehensive understanding of endothelial cell lineage specification will advance cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures preferentially regulate cell identity genes. We thus systematically investigate the epigenetic landscape of endothelial cell lineage and identify MECOM to be the leading candidate as an endothelial cell lineage regulator. Single-cell RNA-Seq analysis verifies that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide endothelial cells derived from induced pluripotent stem cells. Our experiments demonstrate that MECOM depletion impairs human endothelial cell differentiation, functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate endothelial cell identity genes. Further, we identify and verify the VEGF signaling pathway to be a key target of MECOM. Our work provides important insights into epigenetic regulation of cell identity and uncovered MECOM as an endothelial cell lineage regulator., (© 2023. The Author(s).)

Protein phosphorylation is a post-translational modification crucial for many cellular processes and protein functions. Accurate identification and quantification of protein phosphosites at the proteome-wide level are challenging, not least because efficient tools for protein phosphosite false localization rate (FLR) control are lacking. Here, we propose DeepFLR, a deep learning-based framework for controlling the FLR in phosphoproteomics. DeepFLR includes a phosphopeptide tandem mass spectrum (MS/MS) prediction module based on deep learning and an FLR assessment module based on a target-decoy approach. DeepFLR improves the accuracy of phosphopeptide MS/MS prediction compared to existing tools. Furthermore, DeepFLR estimates FLR accurately for both synthetic and biological datasets, and localizes more phosphosites than probability-based methods. DeepFLR is compatible with data from different organisms, instruments types, and both data-dependent and data-independent acquisition approaches, thus enabling FLR estimation for a broad range of phosphoproteomics experiments., (© 2023. The Author(s).)

Cellular senescence contributes to tissue homeostasis and age-related pathologies. However, how senescence is initiated in stressed cells remains vague. Here, we discover that exposure to irradiation, oxidative or inflammatory stressors induces transient biogenesis of primary cilia, which are then used by stressed cells to communicate with the promyelocytic leukemia nuclear bodies (PML-NBs) to initiate senescence responses in human cells. Mechanistically, a ciliary ARL13B-ARL3 GTPase cascade negatively regulates the association of transition fiber protein FBF1 and SUMO-conjugating enzyme UBC9. Irreparable stresses downregulate the ciliary ARLs and release UBC9 to SUMOylate FBF1 at the ciliary base. SUMOylated FBF1 then translocates to PML-NBs to promote PML-NB biogenesis and PML-NB-dependent senescence initiation. Remarkably, Fbf1 ablation effectively subdues global senescence burden and prevents associated health decline in irradiation-treated mice. Collectively, our findings assign the primary cilium a key role in senescence induction in mammalian cells and, also, a promising target in future senotherapy strategies., (© 2023. The Author(s).)

Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe 3+ , and natural bioactive compound curcumin with an ideal API content and pH-responsive release profile for continuous spatiotemporal cancer therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), Fe 2+ , biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe 2+ /BV-BR metabolic pathway, further cooperating with released Fe 3+ and curcumin, ultimately eliciting mitochondria damage, membrane disruption, and intracytoplasmic injury. This work not only provides a paradigm for exploiting diversified metabolites for tumor suppression, but also presents a safe and efficient full-API nanodrug, facilitating the practical translation of nanodrugs., (© 2023. The Author(s).)