Color-coded parametric imaging support display of vessel hemorrhage-an in vitro experiment and clinical validation study.

Background: Digital Subtraction Angiography (DSA) is currently the most effective diagnostic method for vascular diseases, but it is still subject to various factors, resulting in uncertain diagnosis. Therefore, a new technology is needed to help clinical doctors improve diagnostic accuracy and efficiency. Purpose: The objective of the study was to investigate the effect of utilizing color-coded parametric imaging techniques on the accuracy of identifying active bleeding through DSA, the widely accepted standard for diagnosing vascular disorders. Methods: Several variables can delay the diagnosis and treatment of active bleeding with DSA. To resolve this, we carried out an in vitro simulation experiment to simulate vascular hemorrhage and utilized five color-coded parameters (area under curve, time to peak, time-of-arrival, transit time, and flow rate of contrast agent) to determine the optimal color coding parameters. We then verified it in a clinical study. Results: Five different color-coded parametric imaging methods were compared and the time-of-arrival color coding was the most efficient technique for diagnosing active hemorrhage, with a statistically significant advantage (P < 0.001). In clinical study, 135 patients (101 with confirmed bleeding and 34 with confirmed no bleeding) were collected. For patients whose bleeding could not be determined using DSA alone (55/101) and whose no bleeding could not be diagnosed by DSA alone (35/55), the combination of time-of-arrival color parametric imaging was helpful for diagnosis, with a statistically significant difference (P < 0.01 and P = 0.01). Conclusions: The time-of-arrival color coding imaging method is a valuable tool for detecting active bleeding. When combined with DSA, it improves the visual representation of active hemorrhage and improves the efficiency of diagnosis.

Does Patellar Denervation with Electrocautery Benefits for Total Knee Arthroplasty without Patellar Resurfacing: A Meta-analysis of Randomized Controlled Trails.

To investigate the effects of patellar denervation (PD) and non-patellar denervation (NPD) after primary total knee arthroplasty (TKA) without patellar resurfacing, this study conducted systematic electronic searches in November 2023 using PubMed, Embase, Web of Science, Cochrane, and Scopus, adhering to Cochrane Collaboration recommendations. Only randomized controlled trials (RCTs) were included. Additionally, a manual search was performed to identify potentially eligible studies from the reference lists of review articles. Two researchers independently conducted literature reviews, data extraction, and risk of bias assessments. The outcome analysis encompassed the incidence of anterior knee pain (AKP), visual analogue scale (VAS), range of motion (ROM), American Knee Society Score (KSS), Oxford Knee Score (OKS), patellar score (PS), complications, and reoperations. Meta-analysis was executed using RevMan 5.3 software. To enhance the credibility of the study, TSA v0.9 software was utilized to perform power analysis on the overall efficacy of primary and secondary outcomes. Twelve studies involving 1745 patients (1587 knees) were included, with 852 undergoing PD and 893 undergoing NPD. Results indicated a superior reduction in AKP incidence in the PD group compared to the NPD group. Statistically significant differences were observed between PD and NPD in KSS, OKS, and PS. However, the upper limit of the 95% confidence interval for each outcome fell below the minimal clinically important difference (MCID). No significant differences were found in VAS and ROM between PD and NPD. Additionally, PD was not associated with an increased incidence of complications or reoperations. Within 12 months and beyond, PD was proven to be a beneficial intervention in reducing AKP following TKA without patellar resurfacing, achieved without an increase in complications or reoperations. Regarding KSS, OKS, and PS, the minimal advantage achievable through PD may not be clinically significant.

Gut microbiota modulating intestinal stem cell differentiation.

Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation. However, when this disordered proliferation continues, it induces the ISC to enter a cancerous state. The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis. Microbiota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors, while in steady state, differentiated colonocytes are able to break down such metabolites, thereby protecting stem cells at the gut crypt. In the future, the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.

A novel lncRNA LOC101928222 promotes colorectal cancer angiogenesis by stabilizing HMGCS2 mRNA and increasing cholesterol synthesis.

BACKGROUND: Metastasis is the leading cause of mortality in patients with colorectal cancer (CRC) and angiogenesis is a crucial factor in tumor invasion and metastasis. Long noncoding RNAs (lncRNAs) play regulatory functions in various biological processes in tumor cells, however, the roles of lncRNAs in CRC-associated angiogenesis remain to be elucidated in CRC, as do the underlying mechanisms. METHODS: We used bioinformatics to screen differentially expressed lncRNAs from TCGA database. LOC101928222 expression was assessed by qRT-PCR. The impact of LOC101928222 in CRC tumor development was assessed both in vitro and in vivo. The regulatory mechanisms of LOC101928222 in CRC were investigated by cellular fractionation, RNA-sequencing, mass spectrometric, RNA pull-down, RNA immunoprecipitation, RNA stability, and gene-specific m6A assays. RESULTS: LOC101928222 expression was upregulated in CRC and was correlated with a worse outcome. Moreover, LOC101928222 was shown to promote migration, invasion, and angiogenesis in CRC. Mechanistically, LOC101928222 synergized with IGF2BP1 to stabilize HMGCS2 mRNA through an m6A-dependent pathway, leading to increased cholesterol synthesis and, ultimately, the promotion of CRC development. CONCLUSIONS: In summary, these findings demonstrate a novel, LOC101928222-based mechanism involved in the regulation of cholesterol synthesis and the metastatic potential of CRC. The LOC101928222-HMGCS2-cholesterol synthesis pathway may be an effective target for diagnosing and managing CRC metastasis.

Hierarchical global and local auxin signals coordinate cellular interdigitation in Arabidopsis.

The development of multicellular tissues requires both local and global coordination of cell polarization, however, the mechanisms underlying their interplay are poorly understood. In Arabidopsis, leaf epidermal pavement cells (PC) develop a puzzle-piece shape locally coordinated through apoplastic auxin signaling. Here we show auxin also globally coordinates interdigitation by activating the TIR1/AFB-dependent nuclear signaling pathway. This pathway promotes a transient maximum of auxin at the cotyledon tip, which then moves across the leaf activating local PC polarization, as demonstrated by locally uncaged auxin globally rescuing defects in tir1;afb1;afb2;afb4;afb5 mutant but not in tmk1;tmk2;tmk3;tmk4 mutants. Our findings show that hierarchically integrated global and local auxin signaling systems, which respectively depend on TIR1/AFB-dependent gene transcription in the nucleus and TMK-mediated rapid activation of ROP GTPases at the cell surface, control PC interdigitation patterns in Arabidopsis cotyledons, revealing a mechanism for coordinating a local cellular process with the development of whole tissues.

Programmable Lanthanide Metal-Organic Framework for Ultra-Efficient Nucleic Acids Extraction and Interaction Analysis.

Efficient, mild, and reversible adsorption of nucleic acids onto nanomaterials represents a promising analytical approach for medical diagnosis. However, there is a scarcity of efficient and reversible nucleic acid adsorption nanomaterials. Additionally, the lack of comprehension of the molecular mechanisms governing their interactions poses significant challenges. These issues hinder the rational design and analytical applications of the nanomaterials. Herein, we propose an ultra-efficient nucleic acid affinity nanomaterial based on programmable lanthanide metal-organic frameworks (Ln-MOFs). Through experiments and density functional theory calculations, a rational design guideline for nucleic acid affinity of Ln-MOF was proposed, and a modular and flexible preparation scheme was provided. Then, Er-TPA (terephthalic acid) MOF emerged as the optimal candidate due to its pore size-independent adsorption and desorption capabilities for nucleic acids, enabling ultra-efficient adsorption (about 150% mass ratio) within 1 min. Furthermore, we elucidate the molecular-level mechanisms underlying the Ln-MOF adsorption of single- and double-stranded DNA and G4 structures. The affinity nanomaterial based on Ln-MOF exhibits robust nucleic acid extraction capability (4-fold higher than commercial reagent kits) and enables mild and reversible CRISPR/Cas9 functional regulation. This method holds significant promise for broad application in DNA/RNA liquid biopsy and gene editing, facilitating breakthroughs in analytical chemistry, pharmacy, and medical research.

Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1H-benzo[d]imidazole (A25) exhibited optimal antifungal activity against Sclerotinia sclerotiorum (S. s.), affording an excellent half-maximal effective concentration (EC50) of 0.158 µg/mL, which was higher than that of the reference agent carbendazim (EC50 = 0.594 µg/mL). Pot experiments revealed that compound A25 (200 µg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A25 and ß-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

Clonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma.

Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses is one of the biggest clinical challenges. TP53 alterations are established high-risk markers and are included in the current disease staging criteria. KRAS is the most frequently mutated gene affecting around 20% of MM patients. Applying Clonal Competition Assays (CCA) by co-culturing color-labeled genetically modified cell models, we recently showed that mono- and biallelic alterations in TP53 transmit a fitness advantage to the cells. Here, we report a similar dynamic for two mutations in KRAS (G12A and A146T), providing a biological rationale for the high frequency of KRAS and TP53 alterations at MM relapse. Resistance mutations, on the other hand, did not endow MM cells with a general fitness advantage but rather presented a disadvantage compared to the wild-type. CUL4B KO and IKZF1 A152T transmit resistance against immunomodulatory agents, PSMB5 A20T to proteasome inhibition. However, MM cells harboring such lesions only outcompete the culture in the presence of the respective drug. To better prevent the selection of clones with the potential of inducing relapse, these results argue in favor of treatment-free breaks or a switch of the drug class given as maintenance therapy. In summary, the fitness benefit of TP53 and KRAS mutations was not treatment-related, unlike patient-derived drug resistance alterations that may only induce an advantage under treatment. CCAs are suitable models for the study of clonal evolution and competitive (dis)advantages conveyed by a specific genetic lesion of interest, and their dependence on external factors such as the treatment.

The clinicopathological features of lung metastases of parathyroid cancinoma.

Parathyroid carcinoma(PC) is an extremely rare malignant tumor of the parathyroid glands. The lung is the most common target organ for PC distant metastases. In this study, twelve patients diagnosed with PC with lung metastases were enrolled in the study. Hematoxylin and Eosin(H&E) stained, immunohistochemical stained and next-generation sequencing (NGS) of a 425-gene panel were performed on tumor tissue samples. At the same time, we also evaluated its histopathologic characteristics. The results indicate that the microscopic examination of metastatic lesions reveals the same structure and characteristics as PC; the tumor was composed of relatively uniform cells organized in nests and separated by thin fibrous bands and abundant blood vessels. Immunohistochemical evaluation of Ki67, CyclinD1, PTH, SYN, CgA, and CD56 was useful in diagnosing PC with lung metastases. The most frequently genetic alterations were mutations of CDC73 and copy number variation (CNV) of MCL1, with a mutation rate of 25 %. In addition, the mutations of CDC73, ATM, TP53, ALK, ERBB2, MAP3K4, TSC1, CCND1 and CNV of CDK4, MCL1, SMARCB1 overlap between metastatic lesions and primary lesions. In conclusions, PC is a rare endocrine malignant tumor that is very difficult to diagnose preoperatively and prone to clinical recurrence or distant metastasis. Genetic mutations, presentation and histological characteristic were the basis for diagnosing PC with lung metastases.

Sedation-free pediatric [18F]FDG imaging on totalbody PET/CT with the assistance of artificial intelligence.

PURPOSE: While sedation is routinely used in pediatric PET examinations to preserve diagnostic quality, it may result in side effects and may affect the radiotracer's biodistribution. This study aims to investigate the feasibility of sedation-free pediatric PET imaging using ultra-fast total-body (TB) PET scanners and deep learning (DL)-based attenuation and scatter correction (ASC). METHODS: This retrospective study included TB PET (uExplorer) imaging of 35 sedated pediatric patients under four years old to determine the minimum effective scanning time. A DL-based ASC method was applied to enhance PET quantification. Both quantitative and qualitative assessments were conducted to evaluate the image quality of ultra-fast DL-ASC PET. Five non-sedated pediatric patients were subsequently used to validate the proposed approach. RESULTS: Comparisons between standard 300-second and ultra-fast 15-second imaging, CT-ASC and DL-ASC ultra-fast 15-second images, as well as DL-ASC ultra-fast 15-second images in non-sedated and sedated patients, showed no significant differences in qualitative scoring, lesion detectability, and quantitative Standard Uptake Value (SUV) (P = ns). CONCLUSIONS: This study demonstrates that pediatric PET imaging can be effectively performed without sedation by combining ultra-fast imaging techniques with a DL-based ASC. This advancement in sedation-free ultra-fast PET imaging holds potential for broader clinical adoption.

Comprehensive analysis of PPP4C's impact on prognosis, immune microenvironment, and immunotherapy response in lung adenocarcinoma using single-cell sequencing and multi-omics.

Background: Elevated PPP4C expression has been associated with poor prognostic implications for patients suffering from lung adenocarcinoma (LUAD). The extent to which PPP4C affects immune cell infiltration in LUAD, as well as the importance of associated genes in clinical scenarios, still requires thorough investigation. Methods: In our investigation, we leveraged both single-cell and comprehensive RNA sequencing data, sourced from LUAD patients, in our analysis. This study also integrated datasets of immune-related genes from InnateDB into the framework. Our expansive evaluation employed various analytical techniques; these included pinpointing differentially expressed genes, constructing WGCNA, implementing Cox proportional hazards models. We utilized these methods to investigate the gene expression profiles of PPP4C within the context of LUAD and to clarify its potential prognostic value for patients. Subsequent steps involved validating the observed enhancement of PPP4C expression in LUAD samples through a series of experimental approaches. The array comprised immunohistochemistry staining, Western blotting, quantitative PCR, and a collection of cell-based assays aimed at evaluating the influence of PPP4C on the proliferative and migratory activities of LUAD cells. Results: In lung cancer, elevated expression levels of PPP4C were observed, correlating with poorer patient prognoses. Validation of increased PPP4C levels in LUAD specimens was achieved using immunohistochemical techniques. Experimental investigations have substantiated the role of PPP4C in facilitating cellular proliferation and migration in LUAD contexts. Furthermore, an association was identified between the expression of PPP4C and the infiltration of immune cells in these tumors. A prognostic framework, incorporating PPP4C and immune-related genes, was developed and recognized as an autonomous predictor of survival in individuals afflicted with LUAD. This prognostic tool has demonstrated considerable efficacy in forecasting patient survival and their response to immunotherapeutic interventions. Conclusion: The involvement of PPP4C in LUAD is deeply intertwined with the tumor's immune microenvironment. PPP4C's over-expression is associated with negative clinical outcomes, promoting both tumor proliferation and spread. A prognostic framework based on PPP4C levels may effectively predict patient prognoses in LUAD, as well as the efficacy of immunotherapy strategy. This research sheds light on the mechanisms of immune interaction in LUAD and proposes a new strategy for treatment.

A rare case of Gynura-segetum-related hepatic sinus obstruction syndrome complicated with alcoholic liver disease.

Hepatic sinus obstruction syndrome (HSOS) is easy to be misdiagnosed or missed, and there is no unified and effective treatment for it. A patient was considered to have Budd-Chiari syndrome. He underwent a transjugular liver biopsy, and pathological examination revealed HSOS without liver cirrhosis. After the failure of anticoagulation therapy, he successfully received a transjugular intrahepatic portosystemic shunt (TIPS). After discharge, he was followed-up for four years with a good prognosis. G. segetum-induced HSOS can be easily overlooked, especially in patients with underlying liver diseases. When medical therapy fails, TIPS can control ascites and portal hypertension, and the long-term prognosis is optimistic.

Preparation of Al@FTCS/P(VDF-HFP) Composite Energetic Materials and Their Reaction Properties.

Strengthening the interfacial contact between the reactive components effectively boosts the energy release of energetic materials. In this study, we aimed to create a close-knit interfacial contact condition between aluminum nanoparticles (Al NPs) and Polyvinylidene fluoride-hexafluoropropylene (P(VDF-HFP)) through hydrolytic adsorption and assembling 1H, 1H, 2H, 2H-Perfluorododecyltrichlorosilane (FTCS) on the surface of Al NPs. Leveraging hydrogen bonding between -CF and -CH and the interaction between C-F⋯F-C groups, the adsorbed FTCS directly leads to the growth of the P(VDF-HFP) coating layer around the treated Al NPs, yielding Al@FTCS/P(VDF-HFP) energetic composites. In comparison with the ultrasonically processed Al/P(VDF-HFP) mixture, thermal analysis reveals that Al@FTCS/P(VDF-HFP) exhibits a 57 °C lower reaction onset temperature and a 1646 J/g increase in heat release. Associated combustion tests demonstrate a 52% shorter ignition delay, 62% shorter combustion time, and a 288% faster pressurization rate. These improvements in energetic characteristics stem from the reactivity activation of FTCS towards Al NPs by the etching effect to the surface Al2O3. Moreover, enhanced interfacial contact facilitated by the FTCS-directed growth of P(VDF-HFP) around Al NPs further accelerates the whole reaction process.

HCV 5-Methylcytosine Enhances Viral RNA Replication through Interaction with m5C Reader YBX1.

Hepatitis C virus (HCV) is a positive-stranded RNA virus that mainly causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Recently we confirmed m5C modifications within NS5A gene of HCV RNA genome. However, the roles of the m5C modification and its interaction with host proteins in regulating HCV's life cycle, remain unexplored. Here, we demonstrate that HCV infection enhances the expression of the host m5C reader YBX1 through the transcription factor MAX. YBX1 acts as an m5C reader, recognizing the m5C-modified NS5A C7525 site in the HCV RNA genome and significantly enhancing HCV RNA stability. This m5C-modification is also required for YBX1 colocalization with lipid droplets and HCV Core protein. Moreover, YBX1 facilitates HCV RNA replication, as well as viral assembly/budding. The tryptophan residue at position 65 (W65) of YBX1 is critical for these functions. Knockout of YBX1 or the application of YBX1 inhibitor SU056 suppresses HCV RNA replication and viral protein translation. To our knowledge, this is the first report demonstrating that the interaction between host m5C reader YBX1 and HCV RNA m5C methylation facilitates viral replication. Therefore, hepatic-YBX1 knockdown holds promise as a potential host-directed strategy for HCV therapy.

Palladium-Catalyzed Asymmetric Desymmetrization for the Simultaneous Construction of Chiral Phosphorus and Quaternary Carbon Stereocenters.

A palladium-catalyzed asymmetric tandem Heck and carbonylation of bisallyl-phosphine oxides has been developed. This desymmetrization process provided an efficient route to the simultaneous synthesis of a chiral P-stereogenic center and a chiral quaternary carbon stereocenter in good yields with good diastereo- and enantioselectivities.

Neuroprotective effect of autologous mitochondrial transplantation against global ischemia/reperfusion injury in a rat model of cardiac arrest.

BACKGROUND: Mitochondria have emerged as a promising target for ischemic disease. A previous study reported the application of mitochondrial transplantation in focal cerebral ischemia/reperfusion injury, but it is unclear whether exogenous mitochondrial transplantation could be a therapeutic strategy for global ischemia/reperfusion injury induced by cardiac arrest. METHODS: We hypothesized that transplantation of autologous mitochondria would rescue hippocampal cells and alleviate neurological impairment after cardiac arrest. In this study, we employed a rat cardiac arrest-global cerebral ischemia injury model (CA-GCII) and transplanted isolated mitochondria intravenously. Behavior test was applied to assess neurological deficit. Apoptosis and mitochondria permeability transition pore opening in hippocampus was determined using immunoblotting and swelling assay, respectively. RESULTS: Transplanted mitochondria distributed throughout hippocampal cells and reduced oxidative stress. An improved neurological outcome was observed in rats receiving autologous mitochondria. In the hippocampus, mitophagy was enhanced while cell apoptosis was induced by ischemia/reperfusion insult was downregulated by mitochondrial transplantation. Mitochondrial permeability transition pore (MPTP) opening in surviving hippocampal cells was also suppressed. CONCLUSIONS: These results indicated that transplantation of autologous mitochondria rescued hippocampal cells from ischemia/reperfusion injury and ameliorated neurological impairment caused by cardiac arrest.

Enabling Modular Click Chemistry Library through Sequential Ligations of Carboxylic Acids and Amines.

High-throughput synthesis and screening of chemical libraries play pivotal roles in drug discovery. Click chemistry has emerged as a powerful strategy for constructing highly modular chemical libraries. However, the development of new click reactions and unlocking new click able building blocks remain exceedingly challenging. Here in , we describe a double-click strategy that enables the sequential ligation of widely available carboxylic acids and amines with fluorosulfuryl isocyanate (FSO 2 NCO) via a modular amidation/SuFEx process. This method provides facile access to chemical libraries of N-fluorosulfonyl amides (RCONHSO 2 F) and N-acylsulfamides (RCONHSO 2 NR ´ R ´´ ) in near-quantitative yields under simple and practical conditions. The robustness and efficiency of this double click strategy is showcased by the facile construction of chemical libraries in 96-well microtiter plates from a large number of carboxylic acids and amines. Preliminary biological activity screening reveals that some compound s  exhibit high antimicrobial activities against Gram-positive bacterium  S. aureus and drug-resistant MRSA (MIC up to 6.25·µg mL-1). These results provide compelling evidence for the potential application of modular click chemistry library as an enabling technology in high-throughput medicinal chemistry.

Tree phytochemical diversity and herbivory are higher in the tropics.

A long-standing but poorly tested hypothesis in plant ecology and evolution is that biotic interactions play a more important role in producing and maintaining species diversity in the tropics than in the temperate zone. A core prediction of this hypothesis is that tropical plants deploy a higher diversity of phytochemicals within and across communities because they experience more herbivore pressure than temperate plants. However, simultaneous comparisons of phytochemical diversity and herbivore pressure in plant communities from the tropical to the temperate zone are lacking. Here we provide clear support for this prediction by examining phytochemical diversity and herbivory in 60 tree communities ranging from species-rich tropical rainforests to species-poor subalpine forests. Using a community metabolomics approach, we show that phytochemical diversity is higher within and among tropical tree communities than within and among subtropical and subalpine communities, and that herbivore pressure and specialization are highest in the tropics. Furthermore, we show that the phytochemical similarity of trees has little phylogenetic signal, indicating rapid divergence between closely related species. In sum, we provide several lines of evidence from entire tree communities showing that biotic interactions probably play an increasingly important role in generating and maintaining tree diversity in the lower latitudes.

Engineering a biomimicking strategy for discovering nonivamide-based quorum-sensing inhibitors for controlling bacterial infection.

The overuse of antibiotics over an extended period has led to increasing antibiotic resistance in pathogenic bacteria, culminating in what is now considered a global health crisis. To tackle the escalating disaster caused by multidrug-resistant pathogens, the development of new bactericides with new action mechanism is highly necessary. In this study, using a biomimicking strategy, a series of new nonivamide derivatives that feature an isopropanolamine moiety [the structurally similar to the diffusible signal factor (DSF) of Xanthomonas spp.] were prepared for serving as potential quorum-sensing inhibitors (QSIs). After screening and investigation of their rationalizing structure-activity relationships (SARs), compound A26 was discovered as the most optimal active molecule, with EC50 values of 9.91 and 7.04 µg mL-1 against Xanthomonas oryzae pv oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). A docking study showed that compound A26 exhibited robust interactions with Glu A: 161 of RpfF, which was strongly evidenced by fluorescence titration assay (KA value for Xoo RpfF-A26 = 104.8709 M-1). Furthermore, various bioassays showed that compound A26 could inhibit various bacterial virulence factors, including biofilm formation, extracellular polysaccharides (EPS), extracellular enzyme activity, DSF production, and swimming motility. In addition, in vivo anti-Xoo results showed that compound A26 had excellent control efficiency (curative activity: 43.55 %; protective activity: 42.56 %), surpassing that of bismerthiazol and thiodiazole copper by approximately 8.0%-37.3 %. Overall, our findings highlight a new paradigm wherein nonivamide derivatives exhibit potential in combating pathogen resistance issues by inhibiting bacterial quorum sensing systems though attributing to their new molecular skeleton, novel mechanisms of action, and non-toxic features.