Automatic cell-type harmonization and integration across Human Cell Atlas datasets.

Harmonizing cell types across the single-cell community and assembling them into a common framework is central to building a standardized Human Cell Atlas. Here, we present CellHint, a predictive clustering tree-based tool to resolve cell-type differences in annotation resolution and technical biases across datasets. CellHint accurately quantifies cell-cell transcriptomic similarities and places cell types into a relationship graph that hierarchically defines shared and unique cell subtypes. Application to multiple immune datasets recapitulates expert-curated annotations. CellHint also reveals underexplored relationships between healthy and diseased lung cell states in eight diseases. Furthermore, we present a workflow for fast cross-dataset integration guided by harmonized cell types and cell hierarchy, which uncovers underappreciated cell types in adult human hippocampus. Finally, we apply CellHint to 12 tissues from 38 datasets, providing a deeply curated cross-tissue database with ∼3.7 million cells and various machine learning models for automatic cell annotation across human tissues.

A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates.

We present a multiomic cell atlas of human lung development that combines single-cell RNA and ATAC sequencing, high-throughput spatial transcriptomics, and single-cell imaging. Coupling single-cell methods with spatial analysis has allowed a comprehensive cellular survey of the epithelial, mesenchymal, endothelial, and erythrocyte/leukocyte compartments from 5-22 post-conception weeks. We identify previously uncharacterized cell states in all compartments. These include developmental-specific secretory progenitors and a subtype of neuroendocrine cell related to human small cell lung cancer. Our datasets are available through our web interface (https://lungcellatlas.org). To illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signaling and transcription factor hierarchies which we rigorously test using organoid models.

Maternally inherited siRNAs initiate piRNA cluster formation.

PIWI-interacting RNAs (piRNAs) guide transposable element repression in animal germ lines. In Drosophila, piRNAs are produced from heterochromatic loci, called piRNA clusters, which act as information repositories about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a positive feedback loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed before cognate piRNAs are present remains unknown. Here, we report spontaneous de novo piRNA cluster formation from repetitive transgenic sequences. Cluster formation occurs over several generations and requires continuous trans-generational maternal transmission of small RNAs. We discovered that maternally supplied small interfering RNAs (siRNAs) trigger de novo cluster activation in progeny. In contrast, siRNAs are dispensable for cluster function after its establishment. These results reveal an unexpected interplay between the siRNA and piRNA pathways and suggest a mechanism for de novo piRNA cluster formation triggered by siRNAs.

Geminal-atom catalysis for cross-coupling.

Single-atom catalysts (SACs) have well-defined active sites, making them of potential interest for organic synthesis1-4. However, the architecture of these mononuclear metal species stabilized on solid supports may not be optimal for catalysing complex molecular transformations owing to restricted spatial environment and electronic quantum states5,6. Here we report a class of heterogeneous geminal-atom catalysts (GACs), which pair single-atom sites in specific coordination and spatial proximity. Regularly separated nitrogen anchoring groups with delocalized π-bonding nature in a polymeric carbon nitride (PCN) host7 permit the coordination of Cu geminal sites with a ground-state separation of about 4 Å at high metal density8. The adaptable coordination of individual Cu sites in GACs enables a cooperative bridge-coupling pathway through dynamic Cu-Cu bonding for diverse C-X (X = C, N, O, S) cross-couplings with a low activation barrier. In situ characterization and quantum-theoretical studies show that such a dynamic process for cross-coupling is triggered by the adsorption of two different reactants at geminal metal sites, rendering homo-coupling unfeasible. These intrinsic advantages of GACs enable the assembly of heterocycles with several coordination sites, sterically congested scaffolds and pharmaceuticals with highly specific and stable activity. Scale-up experiments and translation to continuous flow suggest broad applicability for the manufacturing of fine chemicals.

A human embryonic limb cell atlas resolved in space and time.

Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months1. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common2. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.

A Non-canonical PDK1-RSK Signal Diminishes Pro-caspase-8-Mediated Necroptosis Blockade.

Necroptosis induction in vitro often requires caspase-8 (Casp8) inhibition by zVAD because pro-Casp8 cleaves RIP1 to disintegrate the necrosome. It has been unclear how the Casp8 blockade of necroptosis is eliminated naturally. Here, we show that pro-Casp8 within the necrosome can be inactivated by phosphorylation at Thr265 (pC8T265). pC8T265 occurs in vitro in various necroptotic cells and in the cecum of TNF-treated mice. p90 RSK is the kinase of pro-Casp8. It is activated by a mechanism that does not need ERK but PDK1, which is recruited to the RIP1-RIP3-MLKL-containing necrosome. Phosphorylation of pro-Casp8 at Thr265 can substitute for zVAD to permit necroptosis in vitro. pC8T265 mimic T265E knockin mice are embryonic lethal due to unconstrained necroptosis, and the pharmaceutical inhibition of RSK-mediated pC8T265 diminishes TNF-induced cecum damage and lethality in mice by halting necroptosis. Thus, phosphorylation of pro-Casp8 at Thr265 by RSK is an intrinsic mechanism for passing the Casp8 checkpoint of necroptosis.

Unraveling the molecular mechanism for enhanced gas adsorption in mixed-metal MOFs via solid-state NMR spectroscopy.

The incorporation of multiple metal ions in metal-organic frameworks (MOFs) through one-pot synthesis can induce unique properties originating from specific atomic-scale spatial apportionment, but the extraction of this crucial information poses challenges. Herein, nondestructive solid-state NMR spectroscopy was used to discern the atomic-scale metal apportionment in a series of bulk Mg1-xCox-MOF-74 samples via identification and quantification of eight distinct arrangements of Mg/Co ions labeled with a 13C-carboxylate, relative to Co content. Due to the structural characteristics of metal-oxygen chains, the number of metal permutations is infinite for Mg1-xCox-MOF-74, making the resolution of atomic-scale metal apportionment particularly challenging. The results were then employed in density functional theory calculations to unravel the molecular mechanism underlying the macroscopic adsorption properties of several industrially significant gases. It is found that the incorporation of weak adsorption sites (Mg2+ for CO and Co2+ for CO2 adsorption) into the MOF structure counterintuitively boosts the gas adsorption energy on strong sites (Co2+ for CO and Mg2+ for CO2 adsorption). Such effect is significant even for Co2+ remote from Mg2+ in the metal-oxygen chain, resulting in a greater enhancement of CO adsorption across a broad composition range, while the enhancement of CO2 adsorption is restricted to Mg2+ with adjacent Co2+. Dynamic breakthrough measurements unambiguously verified the trend in gas adsorption as a function of metal composition. This research thus illuminates the interplay between atomic-scale structures and macroscopic gas adsorption properties in mixed-metal MOFs and derived materials, paving the way for developing superior functional materials.

SOX9 maintains human foetal lung tip progenitor state by enhancing WNT and RTK signalling.

The balance between self-renewal and differentiation in human foetal lung epithelial progenitors controls the size and function of the adult organ. Moreover, progenitor cell gene regulation networks are employed by both regenerating and malignant lung cells, where modulators of their effects could potentially be of therapeutic value. Details of the molecular networks controlling human lung progenitor self-renewal remain unknown. We performed the first CRISPRi screen in primary human lung organoids to identify transcription factors controlling progenitor self-renewal. We show that SOX9 promotes proliferation of lung progenitors and inhibits precocious airway differentiation. Moreover, by identifying direct transcriptional targets using Targeted DamID, we place SOX9 at the centre of a transcriptional network, which amplifies WNT and RTK signalling to stabilise the progenitor cell state. In addition, the proof-of-principle CRISPRi screen and Targeted DamID tools establish a new workflow for using primary human organoids to elucidate detailed functional mechanisms underlying normal development and disease.

The changing mouse embryo transcriptome at whole tissue and single-cell resolution.

During mammalian embryogenesis, differential gene expression gradually builds the identity and complexity of each tissue and organ system1. Here we systematically quantified mouse polyA-RNA from day 10.5 of embryonic development to birth, sampling 17 tissues and organs. The resulting developmental transcriptome is globally structured by dynamic cytodifferentiation, body-axis and cell-proliferation gene sets that were further characterized by the transcription factor motif codes of their promoters. We decomposed the tissue-level transcriptome using single-cell RNA-seq (sequencing of RNA reverse transcribed into cDNA) and found that neurogenesis and haematopoiesis dominate at both the gene and cellular levels, jointly accounting for one-third of differential gene expression and more than 40% of identified cell types. By integrating promoter sequence motifs with companion ENCODE epigenomic profiles, we identified a prominent promoter de-repression mechanism in neuronal expression clusters that was attributable to known and novel repressors. Focusing on the developing limb, single-cell RNA data identified 25 candidate cell types that included progenitor and differentiating states with computationally inferred lineage relationships. We extracted cell-type transcription factor networks and complementary sets of candidate enhancer elements by using single-cell RNA-seq to decompose integrative cis-element (IDEAS) models that were derived from whole-tissue epigenome chromatin data. These ENCODE reference data, computed network components and IDEAS chromatin segmentations are companion resources to the matching epigenomic developmental matrix, and are available for researchers to further mine and integrate.

Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.

BACKGROUND: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-µg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose. RESULTS: Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2. CONCLUSIONS: In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).

Thermopower in Underpotential Deposition-Based Molecular Junctions.

Underpotential deposition (UPD) is an intriguing means for tailoring the interfacial electronic structure of an adsorbate at a substrate. Here we investigate the impact of UPD on thermoelectricity occurring in molecular tunnel junctions based on alkyl self-assembled monolayers (SAMs). We observed noticeable enhancements in the Seebeck coefficient of alkanoic acid and alkanethiol monolayers, by up to 2- and 4-fold, respectively, upon replacement of a conventional Au electrode with an analogous bimetallic electrode, Cu UPD on Au. Quantum transport calculations indicated that the increased Seebeck coefficients are due to the UPD-induced changes in the shape or position of transmission resonances corresponding to gateway orbitals, which depend on the choice of the anchor group. Our work unveils UPD as a potent means for altering the shape of the tunneling energy barrier at the molecule-electrode contact of alkyl SAM-based junctions and hence enhancing thermoelectric performance.

Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony-stimulating factor following chemotherapy: Triangulation of evidence using population-based cohort and Mendelian randomization analyses.

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

Open conformation of tetraspanins shapes interaction partner networks on cell membranes.

Tetraspanins, including CD53 and CD81, regulate a multitude of cellular processes through organizing an interaction network on cell membranes. Here, we report the crystal structure of CD53 in an open conformation poised for partner interaction. The large extracellular domain (EC2) of CD53 protrudes away from the membrane surface and exposes a variable region, which is identified by hydrogen-deuterium exchange as the common interface for CD53 and CD81 to bind partners. The EC2 orientation in CD53 is supported by an extracellular loop (EC1). At the closed conformation of CD81, however, EC2 disengages from EC1 and rotates toward the membrane, thereby preventing partner interaction. Structural simulation shows that EC1-EC2 interaction also supports the open conformation of CD81. Disrupting this interaction in CD81 impairs the accurate glycosylation of its CD19 partner, the target for leukemia immunotherapies. Moreover, EC1 mutations in CD53 prevent the chemotaxis of pre-B cells toward a chemokine that supports B-cell trafficking and homing within the bone marrow, a major CD53 function identified here. Overall, an open conformation is required for tetraspanin-partner interactions to support myriad cellular processes.

Improved redox homeostasis owing to the up-regulation of one-carbon metabolism and related pathways is crucial for yeast heterosis at high temperature.

Heterosis or hybrid vigor is a common phenomenon in plants and animals; however, the molecular mechanisms underlying heterosis remain elusive, despite extensive studies on the phenomenon for more than a century. Here we constructed a large collection of F1 hybrids of Saccharomyces cerevisiae by spore-to-spore mating between homozygous wild strains of the species with different genetic distances and compared growth performance of the F1 hybrids with their parents. We found that heterosis was prevalent in the F1 hybrids at 40°C. A hump-shaped relationship between heterosis and parental genetic distance was observed. We then analyzed transcriptomes of selected heterotic and depressed F1 hybrids and their parents growing at 40°C and found that genes associated with one-carbon metabolism and related pathways were generally up-regulated in the heterotic F1 hybrids, leading to improved cellular redox homeostasis at high temperature. Consistently, genes related with DNA repair, stress responses, and ion homeostasis were generally down-regulated in the heterotic F1 hybrids. Furthermore, genes associated with protein quality control systems were also generally down-regulated in the heterotic F1 hybrids, suggesting a lower level of protein turnover and thus higher energy use efficiency in these strains. In contrast, the depressed F1 hybrids, which were limited in number and mostly shared a common aneuploid parental strain, showed a largely opposite gene expression pattern to the heterotic F1 hybrids. We provide new insights into molecular mechanisms underlying heterosis and thermotolerance of yeast and new clues for a better understanding of the molecular basis of heterosis in plants and animals.

Comparative efficacy and safety of extended adjuvant endocrine therapy for hormone receptor-positive early breast cancer: a Bayesian network meta-analysis.

PURPOSE: Optimal extended adjuvant endocrine therapy (ET) duration and strategy for hormone receptor-positive (HR +) early breast cancer remain unclear. In this network meta-analysis (NMA), the efficacy and safety of all available extended adjuvant ETs were compared and ranked. METHODS: PubMed, Embase, and Cochrane Library and abstracts presented at ASCO, SABCS, and ESMO were searched on March 5, 2022. Fourteen randomized controlled trials (RCTs) comprising eight extended adjuvant ETs for HR + breast cancer and 38,070 patients were analyzed. Main outcomes were disease-free survival (DFS), overall survival (OS), grade ≥ 3 adverse events (AEs), and contralateral breast cancer (CBC). Direct and indirect comparisons were integrated via Bayesian NMA. Hierarchical cluster analysis was performed to jointly rank efficacy and safety outcomes. RESULTS: Compared with that of 5 year ET, extended 10 year aromatase inhibitor (AI) treatment provided the greatest DFS benefit (HR = 0.45, 95%CrI 0.23-0.83), whereas no strategy differed significantly in terms of the other main outcomes. Extended 10 year AI treatment was the preferred strategy for DFS improvement and CBC prevention (surface under the cumulative ranking curve: 93.51% and 91.29% probability, respectively). All strategies had comparable safeties (grade ≥ 3 AEs). Compared with that of 5 year ET, 10 year extended AI significantly increased arthralgia (OR = 1.65, 95%CrI 1.02-2.93) and osteoporosis (OR = 3.33, 95%CrI 1.19-9.68). CONCLUSION: Extended 10 year AI therapy may be optimal for HR + early breast cancer given its relatively high efficacy and safety.

The Developed Wave Cancellation Theory Contributing to Understand Wave Absorption Mechanism of ZIF Derivatives with Controllable Electromagnetic Parameters.

How to better understand the influence of electromagnetic parameters on the absorbing properties of electromagnetic wave absorbers (EMAs) is an essential prerequisite for further synthesis and development of high-performance EMAs. In this work, an improved wave cancellation theory is used as a guiding principle to prepare N-doped carbon-coated cobalt nanoparticles (Co@NC) using ZIF-8@ZIF-67 as the precursor, thus enabling controllable electromagnetic parameters by regulating the conduction loss and dipole polarization ability. The Co@NC generated by pyrolysis at 700 °C under H2 atmosphere presents an optimized absorption performance. Benefiting from developed wave cancellation theory, the thickness of the film can be accurately adjusted so that the difference between the amplitude of the reflected and transmitted electromagnetic waves is only 0.001 and the phase difference is 180.05°, thus achieving a minimum reflection loss (RLmin (dB)) of -64.0 dB. Meanwhile, a maximum effective absorption bandwidth of 5.4 GHz is achieved simultaneously attributing to its most suitable electromagnetic parameters. Accordingly, the current research based on wave cancellation theory significantly contributes to understand the relationships between electromagnetic parameters and wave absorption properties, therefore providing a theoretical insight into the further development of high-performance EMAs.

Simultaneously Engineering the First and Second Coordination Shells of Single Iron Catalysts for Enhanced Oxygen Reduction.

The atomically dispersed Fe-N4 active site presents enormous potential for various renewable energy conversions. Despite its already remarkable catalytic performance, the local atomic microenvironment of each Fe atom can be regulated to further enhance its efficiency. Herein, a novel conceptual strategy that utilizes a simple salt-template polymerization method to simultaneously adjust the first coordination shell (Fe-N3 S1 ) and second coordination shell (C-S-C, a structure similar to thiophene) of Fe-N4 isolated atoms is proposed. Theoretical studies suggest that this approach can redistribute charge density in the MN4 moiety, lowering the d-band center of the metal site. This weakens the binding of oxygenated intermediates, enhancing oxygen reduction reaction (ORR) activity when compared to only implementing coordination shell regulation. Based on the above discovery, a single Fe atom electrocatalyst with the optimal Fe-N3 S1 -S active moiety incorporated in nitrogen, sulfur co-doped graphene (Fe-SAc/NSG) is designed and synthesized. The Fe-SAc/NSG catalyst exhibits excellent alkaline ORR activity, exceeding benchmark Pt/C and most Fe-SAc ORR electrocatalysts, as well as superior stability in Zn-air battery. This work aims to pave the way for creating highly active single metal atom catalysts through the localized regulation of their atomic structure.

Visualization of Multiphase Reactive Flow and Mass Transfer in Functionalized Microfluidic Porous Media.

Multiphase reactive flow in porous media is an important research topic in many natural and industrial processes. In the present work, photolithography is adopted to fabricate multicomponent mineral porous media in a microchannel, microfluidics experiments are conducted to capture the multiphase reactive flow, methyl violet 2B is employed to visualize the real-time concentration field of the acid solution and a sophisticated image processing method is developed to obtain the quantitative results of the distribution of different phases. With the advanced methods, experiments are conducted with different acid concentration and inlet velocity in different porous structures with different phenomena captured. Under a low acid concentration, the reaction will be single phase. In the gaseous cases with higher acid concentration, preferential flow paths with faster flow and reaction are formed by the multiphase hydrodynamic instabilities. In the experiments with different inlet velocities, it is observed that a higher inlet velocity will lead to a faster reaction but less gas bubbles generated. In contrast, more gas bubbles would be generated and block the flow and reaction under a lower inlet velocity. Finally, in heterogeneous structures, fractures or cavities would significantly redirect the flow and promote the formation of preferential flow path nearby.

Engineering Assembly of Plasmonic Virus-Like Gold SERS Nanoprobe Guided by Intelligent Dual-Machine Nanodevice for High-Performance Analysis of Tetracycline.

Accurate detection of trace tetracyclines (TCs) in complex matrices is of great significance for food and environmental safety monitoring. However, traditional recognition and amplification tools exhibit poor specificity and sensitivity. Herein, a novel dual-machine linkage nanodevice (DMLD) is proposed for the first time to achieve high-performance analysis of TC, with a padlock aptamer component as the initiation command center, nucleic acid-encoded multispike virus-like Au nanoparticles (nMVANs) as the signal indicator, and cascade walkers circuit as the processor. The existence of spike vertices and interspike nanogaps in MVANs enables intense electromagnetic near-field focusing, allowing distinct surface-enhanced Raman scattering (SERS) activity. Moreover, through the sequential activation between multistage walker catalytic circuits, the DLMD system converts the limited TC recognition into massive engineering assemblies of SERS probes guided by DNA amplicons, resulting in synergistic enhancement of bulk plasmonic hotspot entities. The continuously guaranteed target recognition and progressively promoted signal enhancement ensure highly specific amplification analysis of TC, with a detection limit as low as 7.94 × 10-16  g mL-1 . Furthermore, the reliable recoveries in real samples confirm the practicability of the proposed sensing platform, highlighting the enormous potential of intelligent nanomachines for analyzing the trace hazards in the environment and food.

Sea Anemone-Inspired Slippery Liquid-Infused Porous Surface (SLIPS) with Bionic Cilia for Responsive 4D Antifouling.

The formation process of biofouling is actually a 4D process with both spatial and temporal dimensions. However, most traditional antifouling coatings, including slippery liquid-infused porous surface (SLIPS), are limited to performing antifouling process in the 2D coating plane. Herein, inspired by the defensive behavior of sea anemones' wielding toxic tentacles, a "4D SLIPS" (FSLIPS) is constructed with biomimetic cilia via a magnetic field self-assembly method for antifouling. The bionic cilia move in 3D space driven by an external magnetic field, thereby preventing the attachment of microorganisms. The FSLIPS releases the gaseous antifoulant (nitric oxide) at 1D time in response to light, thereby achieving a controllable biocide effect on microorganisms. The FSLIPS regulates the movement of cilia via the external magnetic field, and controls the release of NO overtime via the light response, so as to adjust the antifouling modes on demand during the day or night. The light/magnetic response mechanism endow the FSLIPS with the ability to adjust the antifouling effect in the 4D dimension of 1D time and 3D space, effectively realizing the intelligence, multi-dimensionality and precision of the antifouling process.