Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms.

The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, effectors of the SidE family interfere with host protein ubiquitination in a process that involves production of phosphoribosyl ubiquitin (PR-Ub). Here, we show that effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (SHxxxE) present in a large family of toxins from diverse bacterial pathogens. Thus, our study sheds light on the mechanisms by which a pathogen maintains ubiquitin homeostasis and identifies a family of enzymes capable of protein AMPylation.

Sidelobe suppression for accelerating beams.

Although the control of trajectory, amplitude and beam-width in accelerating beams have been extensively investigated, sidelobes manipulation of such beams, which is required in many applications, has been surprisingly under-researched. This paper presents an approach for the generating of accelerating beams with significantly reduced sidelobes. The proposed method encompasses a two-step angular spectrum design, including employing a general model to establish the phase distribution and applying a stochastic parallel gradient descent (SPGD) algorithm to optimize the binary amplitude modulation. Experimental results confirm that the sidelobe intensity of accelerating beams can be reduced by over 50% with our method, thereby enhancing their applicability in many fields, such as micro-machining, particle manipulation, and optical communication.

Evaluation of quercetin in alleviating the negative effects of high soybean meal diet on spotted sea bass Lateolabrax maculatus.

The aim of this study was to investigate the effects of quercetin (QUE) on alleviating the negative effects of high soybean meal diet for spotted sea bass Lateolabrax maculatus. A healthy control group fed a 44% fishmeal diet was used, while the induction control group replaced 50% fishmeal with soybean meal. Subsequently, QUE was added at concentrations of 0.25, 0.50, 0.75, and 1.00 g/kg in the experimental groups. A total of 540 tailed spotted sea bass were randomly divided into 6 groups and fed the corresponding diet for 56 days. The results showed that 40% soybean meal significantly decreased the growth performance and immunity, increased the intestinal mucosal permeability, and caused damage to the intestinal tissue morphology; moreover, there were alterations observed in the composition of the intestinal microbiota, accompanied by detectable levels of saponins in the metabolites. However, the addition of QUE did not yield significant changes in growth performance; instead, it notably reduced the permeability of the intestinal mucosa, improved the body's immunity and the structural integrity of the intestinal tissue, increased the proportion of Proteobacteria, and enhanced the richness and diversity of intestinal microorganisms to a certain extent. In addition, QUE up-regulate the metabolism of amino acids and their derivatives and energy-related metabolites such as uridine and guanosine; furthermore, it appears to regulate transporters through the ABC transporters pathway to promote the absorption and utilization of QUE by enterocytes.

The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment.

Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment.

Mechanism of miR-98-5p in gastric cancer cell proliferation, migration, and invasion through the USP44/CTCFL axis.

Objectives: Gastric cancer (GC) is the leading digestive malignancy with high incidence and mortality rate. microRNAs (miRs) play an important role in GC progresssion. This study aimed to investigate the effect of miR-98-5p on proliferation, migration, and invasion of GC cells. Methods: The expression levels of miR-98-5p, ubiquitin specific peptidase 44 (USP44), and CCCTCbinding factor-like (CTCFL) in GC tissues and cells were identified using reversetranscription quantitative polymerase chain reaction and Western blot assay. The relationship between miR-98-5p expression/USP44 and the clinicopathological features in GC patients was analyzed. GC cell proliferation, invasion, and migration were evaluated by cell counting kit-8 and clone formation assays and Transwell assays. The bindings of miR-98-5p to USP44 and USP44 to CTCFL were examined using dualluciferase assay and co-immunoprecipitation. GC cells were treated with MG132 and the ubiquitination level of CTCFL was examined using ubiquitination assay. Rescue experiments were performed to verify the roles of USP44 and CTCFL in GC cells. Results: miR-98-5p was downregulated in GC. miR-98-5p overexpression inhibited the proliferation, migration, and invasion of GC cells. miR-98-5p inhibited USP44 expression. USP44 bound to CTCFL and limited ubiquitination degradation of CTCFL. Overexpression of USP44 and CTCFL attenuated the inhibitory effects of miR-98-5p overexpression on GC cell progression. Conclusion: miR-98-5p overexpression limited USP44-mediated CTCFL deubiquitination, and suppressed CTCFL expression, mitigating GC cell proliferation, migration, and invasion.

Effects of Lycium barbarum polysaccharides supplemented to high soybean meal diet on immunity and hepatic health of spotted sea bass Lateolabrax maculatus.

High soybean meal diet (HSBMD) decreased the immunity and damaged the liver health of spotted sea bass; in this study, Lycium barbarum polysaccharides (LBP) was added to HSBMD to explore its effects on the immunity and liver health. The diet with 44% fish meal content was designed as a blank control. On this basis, soybean meal was used to replace 50% fish meal as HSBMD, and LBP was added in HSBMD in gradient (1.0, 1.5, 2.0 g/kg) as the experimental diet. 225-tailed spotted sea bass with initial body weight of 44.52 ± 0.24 g were randomly divided into 5 groups and fed the corresponding diet for 52 days, respectively. The results show that: after ingestion of HSBMD, the immunity of spotted sea bass decreased slightly and hepatic tissue was severely damaged. And the addition of LBP significantly improved the immune capacity and protected the hepatic health. Specifically, the activities of serum lysozyme (LZM), immunoglobulin M (IgM), liver acid phosphatase (ACP) and alkaline phosphatase (AKP) were increased, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly decreased, and hepatic morphology was improved. In the analysis of transcriptome results, it was found that toll-like receptor 3 (TLR3) and toll-like receptor 5 (TLR5) were down-regulated in toll-like receptor signaling pathway. And LBP may protect hepatic health by regulating Glycolysis/Gluconeogenesis, Insulin signaling pathway, Steroid biosynthesis and other glucolipid-related pathways. In conclusion, the addition of LBP in HSBMD can improve the immunity and protect the hepatic health of spotted sea bass, and its mechanism may be related to glucose and lipid metabolism.

A 10-m annual grazing intensity dataset in 2015-2021 for the largest temperate meadow steppe in China.

Mapping grazing intensity (GI) using satellites is crucial for developing adaptive utilization strategies according to grassland conditions. Here we developed a monitoring framework based on a paired sampling strategy and the classification probability of random forest algorithm to produce annual grazing probability (GP) and GI maps at 10-m spatial resolution from 2015 to 2021 for the largest temperate meadow in China (Hulun Buir grasslands), by harmonized Landsat 7/8 and Sentinel-2 images. The GP maps used values of 0-1 to present detailed grazing gradient information. To match widely used grazing gradients, annual GI maps with ungrazed, moderately grazed, and heavily grazed levels were generated from the GP dataset with a decision tree. The GI maps for 2015-2021 had an overall accuracy of more than 0.97 having significant correlations with the statistical data at city (r = 0.51) and county (r = 0.75) scales. They also effectively captured the GI gradients at site scale (r = 0.94). Our study proposed a monitoring approach and presented annual 10-m grazing information maps for sustainable grassland management.

Periodic diffractive optical element for high-density and large-scale spot array structured light projection.

Structured light projection has been widely used for depth sensing in computer vision. Diffractive optical elements (DOEs) play a crucial role in generating structured light projected onto objects, and spot array is a common projection pattern. However, the primary metrics of the spot array, including density and field of view, are restricted by the principle of diffraction and its calculation. In this paper, a novel, to the best of our knowledge, method is proposed to achieve high-density periodic spot array on a large scale. Further, periodic DOEs, for the first time, are optimized to increase the density of the spot array without decreasing the periods of the DOE. Simulation and experimental results of high-density and large-scale spot array structured light projection are presented, demonstrating the effectiveness of the proposed method.

China's strictest water policy: Reversing water use trends and alleviating water stress.

Growing water problems have promoted the Chinese government to implement the strictest water resources management system (SWRMS), the first national policy that puts into practice the concept of "safe operating space" for human water use. Here, we investigate the impact of the SWRMS on China's water use and water stress based on a newly compiled high-resolution and multi-sectoral water use dataset. Results indicate that China's total water use (TWU) increased significantly from 549 km3 yr-1 to 610 km3 yr-1 between 2000 and 2012 (i.e., the pre-SWRMS period), but decreased remarkably in the post-SWRMS period (2012-2020), reaching 565 km3 yr-1 by the year 2020. The decline in TWU was attributed to the improvements of irrigation and industrial water use efficiency (WUE), which were strictly controlled by the SWRMS at various administrative levels of China. The improved WUE has yielded about ∼90 km3 of water savings per year, freeing 17 prefectures from extreme water stress that affects 6% of China's population and 10% of its GDP. Although the improved WUE caused a significant decrease in TWU, the reduction in China's average water stress was insignificant due to the considerable influence of water availability. We further identified hotspots with great potential for water stress reduction, mainly in northwestern China, and hotspots at high risks of water security, primarily on the North China Plain. This study underscores the crucial role of the SWRMS in addressing China's water shortage and provides valuable insights to other countries grappling with water problems in defining their own "safe water operating spaces".

Poster Session: Dynamic optomechanical eye model for the validation of peripheral aberration measurement.

Many myopia control products based on the peripheral defocus theory have emerged on the market in the past five years. However, efficient measurement of peripheral aberrations is still not a well-addressed problem. To validate the aberrometer for peripheral aberration measurement, a dynamic wide field optomechanical eye model is designed and fabricated. This model consists of a plano-convex lens representing cornea (f'=30mm), a double-convex lens representing crystalline lens (f'=100mm), and a spherical retinal screen with a 12mm radius. To optimize the quality of spot-field images get from the Hartman-Shack sensor, the materials and surface treatment for the retina are studied. The model has a movable retina to achieve Zernike 4th item (Z4 focus) ranging from -6.28-＋6.84 µm. As for M (Mean sphere equivalent), it can achieve -11.85D-+10.88D at 0° visual field and -6.97D-+5.88D at 30° visual field with a 4mm pupil size. To allow a changing pupil size, a slot at the back of the cornea mount and a series of thin metal sheets with 2, 3, 4, and 6 mm holes are manufactured. Both on-axis aberrations and peripheral aberrations of the eye model are verified by commercial aberrometer VX130 (Luneau Technology, France) and the feasibility of the eye model to mimic a human eye in a peripheral aberration measuring system is illustrated.

Trifunctional Dibromomaleimide Reagents Built Around A Lysine Scaffold Deliver Site-selective Dual-modality Antibody Conjugation.

We describe the synthesis and application of a selection of trifunctional reagents for the dual-modality modification of native, solvent accessible disulfide bonds in trastuzumab. The reagents were developed from the dibromomaleimide (DBM) platform with two orthogonal clickable functional groups built around a lysine core. We also describe the development of an aryl diselenide additive which enables antibody disulfide reduction in 4 minutes and a rapid overall reduction-bridging-double click sequence.

Chameleon-Inspired Mechanochromic Photonic Elastomer with Brilliant Structural Color and Stable Optical Response for Human Motion Visualization.

Flexible and stretchable electronic devices are indispensable parts of wearable devices. However, these electronics employ electrical transducing modes and lack the ability to visually respond to external stimuli, restricting their versatile application in the visualized human-machine interaction. Inspired by the color variation of chameleons' skin, we developed a series of novel mechanochromic photonic elastomers (PEs) with brilliant structural colors and a stable optical response. Typically, these PEs with a sandwich structure were prepared by embedding PS@SiO2 photonic crystals (PCs)within the polydimethylsiloxane (PDMS) elastomer. Benefiting from this structure, these PEs exhibit not only bright structural colors, but also superior structural integrity. Notably, they possess excellent mechanochromism through lattice spacing regulation, and their optical responses are stably maintained even when suffering from 100 stretching-releasing cycles, showing superior stability and reliability and excellent durability. Moreover, a variety of patterned PEs were successfully obtained through a facile mask method, which provides great inspiration to create intelligent patterns and displays. Based on these merits, such PEs can be utilized as visualized wearable devices for detecting various human joint movements in real time. This work offers a new strategy for realizing visualized interactions based on PEs, showing huge application prospects in photonic skins, soft robotics, and human-machine interactions.

Full neurological recovery from severe nonexertional heat stroke with multiple organ dysfunction: A case report.

BACKGROUND: We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3. This report raises awareness among doctors that when heatstroke is diagnosed, comprehensive treatment should be implemented as soon as possible. Moreover, targeted temperature management, combination therapy with hemodialysis and hemoperfusion, and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke. CASE SUMMARY: A previously healthy 67-year-old woman with an initial Glasgow Coma Scale of 3 was found lying prone on the road at noon on a summer day. Laboratory tests revealed multiorgan failure. As soon as heatstroke was diagnosed, comprehensive treatment was implemented. On hospital Day 3, the patient was extubated. Her initial Sequential Organ Failure Assessment score at hospitalization was 14 and decreased to 2 on hospital Day 4. On the seventh day following hospital admission, as the patient's general condition improved, the levels of laboratory test findings decreased rapidly. Finally, the patient gradually recovered with no other neurological symptoms (the Glasgow Coma Scale at discharge was 15, and her ability to walk independently was restored). CONCLUSION: This case demonstrated that targeted temperature management, combination therapy with hemodialysis and hemoperfusion, and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.

Dynamic opto-mechanical eye model with peripheral refractions.

Many myopia control methods based on the peripheral defocus theory have emerged towards applications in recent years. However, peripheral aberration is a critical issue, which is still not well-addressed. To validate the aberrometer for peripheral aberration measurement, a dynamic opto-mechanical eye model with a wide visual field is developed in this study. This model consists of a plano-convex lens representing cornea (f' = 30 mm), a double-convex lens representing crystalline lens (f' = 100 mm), and a spherical retinal screen with a radius of 12 mm. To optimize the quality of spot-field images from the Hartman-Shack sensor, the materials and surface topography for the retina are studied. The model has an adjustable retina to achieve Zernike 4th item (Z4 focus) ranging from -6.28 µm to +6.84 µm. As for mean sphere equivalent, it can achieve -10.52 D to +9.16 D at 0° visual field and -6.97 D to +5.88 D at 30° visual field with a pupil size of 3 mm. To realize a changing pupil size, a slot at the back of the cornea mount and a series of thin metal sheets with 2, 3, 4, and 6 mm holes are generated. Both on-axis aberrations and peripheral aberrations of the eye model are verified by a well-used aberrometer and the eye model to mimic a human eye in a peripheral aberration measurement system is illustrated.

Differentiation of Small Gastrointestinal Stromal Tumor and Gastric Leiomyoma with Contrast-Enhanced CT.

Objective: The value of multiphase contrast-enhanced CT in differentiating gastrointestinal stromal tumors (GISTs) and gastric leiomyomas (GLMs) which were ≤3 cm was evaluated using machine learning. Methods: A retrospective analysis was conducted on 45 cases of small gastric wall submucosal tumors (including 22 GISTs and 23 GLMs) with pathologically confirmed diameter ≤3 cm and completed multiphase CT-enhanced scan images. The CT features including tumor location, maximum diameter, shape, margins, growth pattern, plain/enhanced CT value, cystic degeneration, calcification, ulcer, progressive reinforcement, perilesional lymph nodes, and the CT value ratio of the tumor to the aorta at the same level in the enhanced phase III scan of the two groups were evaluated. Tumor location and maximum diameter were automatically evaluated by machine learning. Results: The GISTs and GLMs with a diameter ≤3 cm showed clear margins, uniform density on plain scan CT, and progressive homogeneous enhancement. The age of the GISTs is greater than that of the GLMs group. The plain scan CT value of the GISTs group was lower than that in the GLMs group. In the GISTs group, the lesions were mostly located in the fundus (68.18%), showing a mixed growth pattern (54.55%), and in the GLMs group, most lesions were located in the cardia (47.82%), showing an intraluminal growth pattern (95.65%). The abovementioned differences were statistically significant. Conclusions: Contrast-enhanced CT has limited value in differentiating small GISTs from GLMs, which are ≤3 cm. Older age (>49.0 years), a low plain CT value (<42.5 Hu), mixed growth inside and outside the cavity, and noncardiac location tended to be the criteria for the diagnosis of small GISTs of the gastric wall.

The effect of thalidomide on the invasive ability of gastric cancer cells by regulating miR-524-5p/FSTL1.

This study aimed to investigate the effect of thalidomide (Thal) regulating microRNA (miR)-524-5p/follistatin-like protein 1 (FSTL1) on the invasion ability of gastric cancer cells. For this purpose, real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the level of miR-524-5p in GES1, SUN-16, MGC-803, SGC-7901, MKN-28, and MKN-45 cells. Then the MGC-803 and MKN-45 cells would proceed to the next research. The MGC-803 and MKN-45 cells were cultured in vitro and added Thal to the final concentration of (6.25, 12.5, 25, 50, 100) µg/mL. The blank control group only added 0.1% dimethyl sulfoxide (DMSO) culture medium, and cultured for 48 hours. CCK8 was used to detect cell proliferation, and Transwell was used to detect cell invasion. The experiment was divided into a blank control group, Thal group (25 µg/mL Thal-treated cells), Thal+inhibitor NC group, and Thal+miR-524-5p inhibitor group (transfected with inhibitor NC and miR-524-5p inhibitor respectively on the basis of Thal group), cultivated for 48 h. The level of miR-524-5p in the cells was detected by RT-qPCR; the cell invasion was detected by Transwell; the expression of matrix metalloproteinase (MMP)-2, MMP-9, FSTL1 protein in the cells was detected by Western blot. The targeting relationship between miR-524-5p and FSTL1 was verified by dual luciferase. Results showed that compared with GES1 cells, the level of miR-524-5p in SUN-16, MGC-803, SGC-7901, MKN-28, and MKN-45 cells decreased (P<0.05). In MGC-803 and MKN-45 cells, compared with the blank control group, the cell proliferation rate and the number of invasions in the (50, 100) µg/mL Thal treatment groups, and the number of invasions in (6.25, 12.5, 25) µg/mL Thal treatment groups decreased (P<0.05). Compared with the blank control group, the level of miR-524-5p in the cells of the Thal group, Thal+inhibitor NC group, and Thal+miR-524-5p inhibitor group increased (P<0.05), the number of invasions, the levels of MMP-2, MMP-9 and FSTL1 proteins in cells decreased (P<0.05); compared with the Thal group and the Thal+inhibitor NC group, the level of miR-524-5p in the cells of the Thal+miR-524-5p inhibitor group decreased (P<0.05), the number of invasions, the levels of MMP-2, MMP-9, and FSTL1 proteins in the cells increased (P<0.05). Dual luciferase verification revealed that there was a targeting relationship between miR-524-5p and FSTL1. In conclusion, that can up-regulate the expression of miR-524-5p to reduce the expression of FSTL1 protein, inhibit the invasion of gastric cancer cells, and achieve alleviation of the disease.

Assembly and purification of AvrSr35-induced Sr35 resistosome and determination of its structure by cryo-EM.

Sr35, a coiled-coil nucleotide-binding leucine-rich repeat receptor (CC-NLR) from the wheat species Triticum monococcum can directly recognize the pathogen avirulence factor AvrSr35 and confers immunity against wheat stem rust caused by Puccinia graminis f.sp. tritici race Ug99. Assembly of a stable Sr35 resistosome induced by AvrSr35 in vitro is usually limited by protein expression and low assembly efficiency. Here, we describe the expression and purification of AvrSr35 and Sr35, in vitro assembly of Sr35 resistosome for structure determination by cryo-EM. For complete details on the use and execution of this protocol, please refer to Zhao et al. (2022).

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

Correlation Between Serum Uric Acid Levels and Coronary Plaque Characteristics on Optical Coherence Tomography.

Elevated serum uric acid (sUA) is associated with increasing risk of coronary heart disease (CHD). However, existing research is limited by potential confounders. Herein, our study aims to probe the association between sUA levels and the morphological characteristics of coronary plaque by a propensity score matching (PSM) analysis.All 420 patients with CHD who had undergone optical coherence tomography of culprit lesions were included. Eligible patients were assigned into 2 groups according to sUA level: high-sUA group (sUA ≥ 6.0 mg/dL) and low-sUA group (sUA < 6.0 mg/dL). PSM was applied to control the balance of baseline characteristics.After PSM, a total of 112 patients were included in our study (56 in each group). The high-sUA group showed a higher prevalence of TCFA (35.7% versus 16.1%, P = 0.03) and macrophage infiltration (33.9% versus 14.3%, P = 0.026) compared with the low-sUA group. Plaques in the high-sUA group had a wider maximum lipid arc (166.51° (115.77°, 224.14°) versus 142.29° (93.95°, 169.06°), P = 0.048), longer calcification length (6.77 (3.90, 20.55) mm versus 4.20 (1.95, 7.45) mm, P = 0.040), and thinner minimum fibrous cap thickness (43.81 (28.17, 62.26) µm versus 92.57 (46.25, 135.37) µm, P = 0.003). Correlation analysis indicated that the sUA value was inversely associated with the minimum fibrous cap thickness (r = -0.332, P = 0.015) and positively associated with the maximum lipid arc (r = 0.399, P = 0.003), average lipid arc (r = 0.347, P = 0.011), and calcification length (r = 0.386, P = 0.006).The relationship between high-sUA levels and typical vulnerable features of plaques persisted after balancing the traditional risk factors.

Pathogen effector AvrSr35 triggers Sr35 resistosome assembly via a direct recognition mechanism.

Nucleotide-binding, leucine-rich repeat receptors (NLRs) perceive pathogen effectors to trigger plant immunity. The direct recognition mechanism of pathogen effectors by coiled-coil NLRs (CNLs) remains unclear. We demonstrate that the Triticum monococcum CNL Sr35 directly recognizes the pathogen effector AvrSr35 from Puccinia graminis f. sp. tritici and report a cryo-electron microscopy structure of Sr35 resistosome and a crystal structure of AvrSr35. We show that AvrSr35 forms homodimers that are disassociated into monomers upon direct recognition by the leucine-rich repeat domain of Sr35, which induces Sr35 resistosome assembly and the subsequent immune response. The first 20 amino-terminal residues of Sr35 are indispensable for immune signaling but not for plasma membrane association. Our findings reveal the direct recognition and activation mechanism of a plant CNL and provide insights into biochemical function of Sr35 resistosome.