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Receptor-like kinases (RLKs) and Receptor-like proteins (RLPs) play crucial roles in plant immunity, growth, and development. Plants deploy a large number of RLKs and RLPs as pattern recognition receptors (PRRs) that detect microbe- and host-derived molecular patterns as the first layer of inducible defense. Recent advances have uncovered novel PRRs, their corresponding ligands, and mechanisms underlying PRR activation and signaling. In general, PRRs associate with other RLKs and function as part of multiprotein immune complexes at the cell surface. Innovative strategies have emerged for the rapid identification of microbial patterns and their cognate PRRs. Successful pathogens can evade or block host recognition by secreting effector proteins to “hide” microbial patterns or inhibit PRR-mediated signaling. Furthermore, newly identified pathogen effectors have been shown to manipulate RLKs controlling growth and development by mimicking peptide hormones of host plants. The ongoing studies illustrate the importance of diverse plant RLKs in plant disease

Nucleotide-binding, leucine-rich repeat receptors (NLRs) initiate immune responses when they sense a pathogen-associated effector. In animals, oligomerization of NLRs upon binding their effectors is key to downstream activity, but plant systems differ in many ways and their activation mechanisms have been less clear. In two papers, Wang et al. studied the composition and structure of an NLR called ZAR1 in the small mustard plant Arabidopsis (see the Perspective by Dangl and Jones). They determined cryo–electron microscopy structures that illustrate differences between inactive and intermediate states. The active, intermediate state of ZAR1 forms a wheel-like pentamer, called the resistosome. In this activated complex, a set of helices come together to form a funnel-shaped structure required for immune responsiveness and association with the plasma membrane. Science , this issue p. eaav5868 , p. eaav5870 ; see also p. 31 Structural, biochemical, and functional studies show how a plant immune resistosome complex mediates cell death and disease resistance. Nucleotide-binding, leucine-rich repeat receptors (NLRs) perceive pathogen effectors to trigger plant immunity. Biochemical mechanisms underlying plant NLR activation have until now remained poorly understood. We reconstituted an active complex containing the Arabidopsis coiled-coil NLR ZAR1, the pseudokinase RKS1, uridylated protein kinase PBL2, and 2′-deoxyadenosine 5′-triphosphate (dATP), demonstrating the oligomerization of the complex during immune activation. The cryo–electron microscopy structure reveals a wheel-like pentameric ZAR1 resistosome. Besides the nucleotide-binding domain, the coiled-coil domain of ZAR1 also contributes to resistosome pentamerization by forming an α-helical barrel that interacts with the leucine-rich repeat and winged-helix domains. Structural remodeling and fold switching during activation release the very N-terminal amphipathic α helix of ZAR1 to form a funnel-shaped structure that is required for the plasma membrane association, cell death triggering, and disease resistance, offering clues to the biochemical function of a plant resistosome.

Nucleotide-binding, leucine-rich repeat receptors (NLRs) initiate immune responses when they sense a pathogen-associated effector. In animals, oligomerization of NLRs upon binding their effectors is key to downstream activity, but plant systems differ in many ways and their activation mechanisms have been less clear. In two papers, Wang et al. studied the composition and structure of an NLR called ZAR1 in the small mustard plant Arabidopsis (see the Perspective by Dangl and Jones). They determined cryo–electron microscopy structures that illustrate differences between inactive and intermediate states. The active, intermediate state of ZAR1 forms a wheel-like pentamer, called the resistosome. In this activated complex, a set of helices come together to form a funnel-shaped structure required for immune responsiveness and association with the plasma membrane. Science , this issue p. eaav5868 , p. eaav5870 ; see also p. 31 Structural, biochemical, and functional studies show how a plant immune resistosome complex mediates cell death and disease resistance. Pathogen recognition by nucleotide-binding (NB), leucine-rich repeat (LRR) receptors (NLRs) plays roles in plant immunity. The Xanthomonas campestris pv. campestris effector AvrAC uridylylates the Arabidopsis PBL2 kinase, and the latter (PBL2 UMP ) acts as a ligand to activate the NLR ZAR1 precomplexed with the RKS1 pseudokinase. Here we report the cryo–electron microscopy structures of ZAR1-RKS1 and ZAR1-RKS1-PBL2 UMP in an inactive and intermediate state, respectively. The ZAR1 LRR domain, compared with animal NLR LRR domains, is differently positioned to sequester ZAR1 in an inactive state. Recognition of PBL2 UMP is exclusively through RKS1, which interacts with ZAR1 LRR . PBL2 UMP binding stabilizes the RKS1 activation segment, which sterically blocks ZAR1 adenosine diphosphate (ADP) binding. This engenders a more flexible NB domain without conformational changes in the other ZAR1 domains. Our study provides a structural template for understanding plant NLRs.

Reactive oxygen species (ROS) are by-products of cellular respiration that can promote oxidative stress and damage cellular proteins and lipids. One canonical role of ROS is to defend the cell against invading bacterial and viral pathogens. Curiously, some viruses, including herpesviruses, thrive despite the induction of ROS, suggesting that ROS are beneficial for the virus. However, the underlying mechanisms remain unclear. Here, we found that ROS impaired interferon response during murine herpesvirus infection and that the inhibition occurred downstream of cytoplasmic DNA sensing. We further demonstrated that ROS suppressed the type I interferon response by oxidizing Cysteine 147 on murine stimulator of interferon genes (STING), an ER-associated protein that mediates interferon response after cytoplasmic DNA sensing. This inhibited STING polymerization and activation of downstream signaling events. These data indicate that redox regulation of Cysteine 147 of mouse STING, which is equivalent to Cysteine 148 of human STING, controls interferon production. Together, our findings reveal that ROS orchestrates anti-viral immune responses, which can be exploited by viruses to evade cellular defenses.

Since the structured dimple surface is one of the important functional drag-reducing surfaces, the research on its efficient fabrication technology is of great significance for the practical application of this surface. Therefore, in order to grind structured dimple surface, a topological mapping grinding method for structured dimple surface was proposed based on grinding kinematics principle and point set topology. Firstly, the topological spaces of the workpiece and the grinding wheel were established, and the topological features of the structured dimple surface and the structured grinding wheel were extracted based on the analysis of the topography features of the structured surface with ordered pattern. Then, the topology mapping equation of the grinding process was constructed based on the analysis of the generating mechanism of the dimple surface about grinding geometry, and the structured grinding wheel was designed according to the topology mapping equation. Finally, according to the grinding geometry simulation, the influence of grinding parameters on the generating of dimple surface topography was studied, and the grinding experiment was carried out. The results show that the structured grinding wheel designed based on the topological features of the structured dimple surface can achieve the grinding of the structured dimple surface. The ground dimple surface is a topological dimple surface, and its feature parameters can be changed with the change of grinding parameters, but the topological feature attributes remain unchanged under the condition of satisfying the proper grinding speed ratio.

The structured groove surface is one of the important surfaces in the field of reducing fluid drag or contact friction. The research on the manufacturing technology of the structured groove drag or friction reduction surface has important theoretical significance and practical value for the engineering application of the theoretical research results of the drag or friction reduction of the surface. In order to grind structured groove surface, a new topological mapping grinding strategy for structured groove surfaces is innovated based on topology. In order to verify the feasibility of this strategy, the topological features of the structured groove surface were firstly analyzed and modeled, and the topological feature parameters were extracted. Based on the feature parameters, the homeomorphic mapping equation of the grinding process is established, and according to the established equation, a circular arc-shaped helical structure grinding wheel with convex properties is designed, and the effect of grinding parameters on the structured groove surface is simulated and analyzed. Finally, a wire-wound structured grinding wheel with a diamond wire saw as the abrasive carrier was manufactured, and the experimental investigation of grinding structured groove surface was carried out. The results show that the innovative topology grinding strategy is feasible; the grinding wheel designed based on the topological features of the structured groove surface can realize the topological mapping grinding of the structured groove surface; the change of grinding parameters can lead to the change of the geometric size of the groove, but the topological properties remain unchanged.

Gene regulatory networks (GRNs) control development via cell type‐specific gene expression and interactions between transcription factors (TFs) and regulatory promoter regions. Plant organ boundaries separate lateral organs from the apical meristem and harbor axillary meristems (AMs). AMs, as stem cell niches, make the shoot a ramifying system. Although AMs have important functions in plant development, our knowledge of organ boundary and AM formation remains rudimentary. Here, we generated a cellular‐resolution genomewide gene expression map for low‐abundance Arabidopsis thaliana organ boundary cells and constructed a genomewide protein–DNA interaction map focusing on genes affecting boundary and AM formation. The resulting GRN uncovers transcriptional signatures, predicts cellular functions, and identifies promoter hub regions that are bound by many TFs. Importantly, further experimental studies determined the regulatory effects of many TFs on their targets, identifying regulators and regulatory relationships in AM initiation. This systems biology approach thus enhances our understanding of a key developmental process. Synopsis The leaf boundary regions separate differentiated organs from undifferentiated stem cells in plants. The gene regulatory network of boundary cells was mapped by combining cell type‐specific genome expression analysis with genomewide yeast one‐hybrid screening. A leaf boundary cell‐specific gene expression map identifies transcriptional signatures and predicts cellular functions. A genomewide protein–DNA interaction map resolved using a yeast one‐hybrid approach uncovers promoter hubs and predicts new regulating transcription factors (TFs). An intermediate‐scale experimental test determined the regulatory effects of many TFs on their targets and identified new regulators and regulatory relationships in boundary and axillary meristem formation. Graphical Abstract The leaf boundary regions separate differentiated organs from undifferentiated stem cells in plants. The gene regulatory network of boundary cells was mapped by combining cell type‐specific genome expression analysis with genomewide yeast one‐hybrid screening.

Chemotherapy remains a prevalent strategy in cancer therapy; however, the emergence of drug resistance poses a considerable challenge to its efficacy. Most drug resistance arises from the accumulation of genetic mutations in a minority of resistant cells. The mechanisms underlying the emergence and progression of cancer resistance from these minority‐resistant cells (MRCs) remain poorly understood. This study employs force‐induced remnant magnetization spectroscopy (FIRMS) alongside various biological investigations to reveal the mechanical pathways for MRCs fostering drug resistance and tumor progression. The findings show that minority Paclitaxel‐resistant cancer cells have enhanced mechanical properties. These cells can transmit high‐intensity forces to surrounding sensitive cells (SCs) through the force transducer, Merlin. This force transmission facilitates the assimilation of surrounding SCs, subsequently strengthening the contraction and adhesion of tumor cells. This process is termed “mechano‐assimilation,” which accelerates the development of drug resistance and tumor progression. Interestingly, disturbances and reductions of mechano‐assimilation within tumors can restore sensitivity to Paclitaxel both in vitro and in vivo. This study provides preliminary evidence highlighting the contribution of MRCs to the development of drug resistance and malignancy, mediated through mechanical interactions. It also establishes a foundation for future research focused on integrating mechanical factors into innovative cancer therapies. This study provides new perspectives into the interactions between mechanical forces and cellular dynamics within the tumor microenvironment, particularly elucidating how minority Paclitaxel‐resistant cancer cells (MRCs) promote tumor progression and treatment resistance through mechanical forces and also providing effective treatment strategies for restoring tumor sensitivity to Paclitaxel.

Genome editing holds great potential for cancer treatment due to the ability to precisely inactivate or repair cancer-related genes. However, delivery of CRISPR/Cas to solid tumours for efficient cancer therapy remains challenging. Here we targeted tumour tissue mechanics via a multiplexed dendrimer lipid nanoparticle (LNP) approach involving co-delivery of focal adhesion kinase (FAK) siRNA, Cas9 mRNA and sgRNA (siFAK + CRISPR-LNPs) to enable tumour delivery and enhance gene-editing efficacy. We show that gene editing was enhanced >10-fold in tumour spheroids due to increased cellular uptake and tumour penetration of nanoparticles mediated by FAK-knockdown. siFAK + CRISPR-PD-L1-LNPs reduced extracellular matrix stiffness and efficiently disrupted PD-L1 expression by CRISPR/Cas gene editing, which significantly inhibited tumour growth and metastasis in four mouse models of cancer. Overall, we provide evidence that modulating the stiffness of tumour tissue can enhance gene editing in tumours, which offers a new strategy for synergistic LNPs and other nanoparticle systems to treat cancer using gene editing.In vivo delivery of the CRISPR/Cas system is a promising cancer therapy approach, but its efficacy is hampered by low penetrability of nanoparticles in the stiff tumour tissue. Here the authors use dendrimer lipid nanoparticles to couple PD-L1 gene editing with knockdown of FAK, a protein involved in cell adhesion, showing that modulation of the mechanical properties of tumour cells leads to enhanced gene editing and tumour growth inhibition in four different animal models.

Riblet surface is a biomimetic surface that not only has the ability to reduce surface drag resistance of mechanical products in fluids, but also improves surface hydrophobicity. Therefore, studying its manufacturing technology has practical significance for solving its engineering applications. In order to grind the riblet surface on the cylindrical workpiece, an innovative hob-grinding strategy for reducing drag on cylindrical riblet surfaces using superhard grinding wheels with spiral abrasive pattern has been developed. To achieve this strategy, firstly, based on the analysis of the geometric topology features of the riblet surface, an engineered CBN grinding wheel with spiral arrangement of abrasive particles was designed based on the principle of gear hobbing machining. Then, the relationship between hob-grinding parameters and abrasive particle arrangement parameters on the parameters of the ground riblets was analyzed, and the process measures to increase the number of riblets on the cylindrical surface, the ratio of the height to spacing of riblets, and the impact on the surface geometry of the riblets were explored. Finally, the surface of the cylindrical riblet surface was ground through experiments, and under the conditions of this experiment, a riblet surface was obtained that its spacing, height, and ratio of the height-spacing were 93.85 µm, 14.65 µm, and 0.156, respectively. The research results indicate that using this strategy can grind the cylindrical riblet surface, and the proposed process strategy of increasing the number of riblets and the ratio of the height to spacing is feasible.