Integrative ATAC-seq and RNA-seq Analysis of the Longissimus Dorsi Muscle of Gannan Yak and Jeryak.

Jeryak is the F1 generation of the cross between Gannan yak and Jersey cattle, which has the advantages of fast growth and high adaptability. The growth and development of skeletal muscle is closely linked to meat production and the quality of meat. However, the molecular regulatory mechanisms of muscle growth differences between Gannan yak and Jeryak analyzed from the perspective of chromatin opening have not been reported. In this study, ATAC-seq was used to analyze the difference of chromatin openness in longissimus muscle of Gannan yak and Jeryak. It was found that chromatin accessibility was more enriched in Jeryak compared to Gannan yak, especially in the range of the transcription start site (TSS) ± 2 kb. GO and KEGG enrichment analysis indicate that differential peak-associated genes are involved in the negative regulation of muscle adaptation and the Hippo signaling pathway. Integration analysis of ATAC-seq and RNA-seq revealed overlapping genes were significantly enriched during skeletal muscle cell differentiation and muscle organ morphogenesis. At the same time, we screened FOXO1, ZBED6, CRY2 and CFL2 for possible involvement in skeletal muscle development, constructed a genes and transcription factors network map, and found that some transcription factors (TFs), including YY1, KLF4, KLF5 and Bach1, were involved in skeletal muscle development. Overall, we have gained a comprehensive understanding of the key factors that impact skeletal muscle development in various breeds of cattle, providing new insights for future analysis of the molecular regulatory mechanisms involved in muscle growth and development.

Proteome Analysis Related to Unsaturated Fatty Acid Synthesis by Interfering with Bovine Adipocyte ACSL1 Gene.

Unsaturated fatty acids (UFAs) in beef play a vital role in promoting human health. Long-chain fatty acyl-CoA synthase 1 (ACSL1) is a crucial gene for UFA synthesis in bovine adipocytes. To investigate the protein expression profile during UFA synthesis, we performed a proteomic analysis of bovine adipocytes by RNA interference and non-interference with ACSL1 using label-free techniques. A total of 3558 proteins were identified in both the NC and si-treated groups, of which 1428 were differentially expressed proteins (DEPs; fold change ≥ 1.2 or ≤ 0.83 and p-value < 0.05). The enrichment analysis of the DEPs revealed signaling pathways related to UFA synthesis or metabolism, including cAMP, oxytocin, fatty acid degradation, glycerol metabolism, insulin, and the regulation of lipolysis in adipocytes (p-value < 0.05). Furthermore, based on the enrichment analysis of the DEPs, we screened 50 DEPs that potentially influence the synthesis of UFAs and constructed an interaction network. Moreover, by integrating our previously published transcriptome data, this study established a regulatory network involving differentially expressed long non-coding RNAs (DELs), highlighting 21 DEPs and 13 DELs as key genes involved in UFA synthesis. These findings present potential candidate genes for further investigation into the molecular mechanisms underlying UFA synthesis in bovines, thereby offering insights to enhance the quality of beef and contribute to consumer health in future studies.

Unlocking the Transcriptional Control of NCAPG in Bovine Myoblasts: CREB1 and MYOD1 as Key Players.

Muscle formation directly determines meat production and quality. The non-SMC condensin I complex subunit G (NCAPG) is strongly linked to the growth features of domestic animals because it is essential in controlling muscle growth and development. This study aims to elucidate the tissue expression level of the bovine NCAPG gene, and determine the key transcription factors for regulating the bovine NCAPG gene. In this study, we observed that the bovine NCAPG gene exhibited high expression levels in longissimus dorsi and spleen tissues. Subsequently, we cloned and characterized the promoter region of the bovine NCAPG gene, consisting of a 2039 bp sequence, through constructing the deletion fragment double-luciferase reporter vector and site-directed mutation-identifying core promoter region with its key transcription factor binding site. In addition, the key transcription factors of the core promoter sequence of the bovine NCAPG gene were analyzed and predicted using online software. Furthermore, by integrating overexpression experiments and the electrophoretic mobility shift assay (EMSA), we have shown that cAMP response element binding protein 1 (CREB1) and myogenic differentiation 1 (MYOD1) bind to the core promoter region (-598/+87), activating transcription activity in the bovine NCAPG gene. In conclusion, these findings shed important light on the regulatory network mechanism that underlies the expression of the NCAPG gene throughout the development of the muscles in beef cattle.

Spatiotemporal evolution characteristics and driving forces of vegetation cover variations in the Chengdu-Chongqing region of China under the background of rapid urbanization.

The research on the spatiotemporal changes and driving factors of ecosystems in rapidly urbanizing regions has always been a topic of widespread concern. As the fourth pole of China's economic development, the research on the Chengdu-Chongqing region has reference significance for the urbanization process of developing countries such as India, Brazil, and South Africa.The normalized difference vegetation index (NDVI) has been widely applied in studies of plant and ecosystem changes. Based on MODIS NDVI data from 2001 to 2020 and meteorological data of the same period, this study reveals the evolution of NDVI in the Chengdu-Chongqing region from three aspects: the spatiotemporal variation characteristics of NDVI, the prediction of future trends in vegetation coverage, and the response of vegetation to climate change and human activities. During the period of plant growth, the mean NDVI achieved a value of 0.78, and the vegetation coverage rate is increasing year by year. According to the Hurst index, the future NDVI in Chengdu-Chongqing region will tend to decrease, and its trend is opposite to that of the past period of time. The Chengdu-Chongqing region vegetation positively affected by human activities is greater than those negatively affected, and in terms of vegetation degradation, the impact of human activities is greater than climate change.

Bioequivalence and Safety Assessment of 2 Formulations of Low-Dose Metformin Hydrochloride under Fasting Conditions in Healthy Chinese Participants: A Randomized Phase 1 Clinical Trial.

The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label, single-dose, 2-period, 2-sequence crossover, single-center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (Cmax ) were within the range of 0.8-1.25. Thirty-five participants completed the trial. The T/R adjusted GMRs (95.7% for Cmax , 98.7% for AUC0→t , 98.8% for AUC0→∞ ) were within the acceptable bioequivalence range of 80%-125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well-tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (www.chinadrugtrials.org.cn; registration no. CTR20190356).

Transcriptome Analysis of mRNA and lncRNA Related to Muscle Growth and Development in Gannan Yak and Jeryak.

The production performance of Jeryak, resulting from the F1 generation of the cross between Gannan yak and Jersey cattle, exhibits a significantly superior outcome compared with that of Gannan yak. Therefore, we used an RNA-seq approach to identify differentially expressed mRNAs (DEMs) and differentially expressed lncRNAs (DELs) influencing muscle growth and development in Gannan yaks and Jeryaks. A total of 304 differentially expressed lncRNAs and 1819 differentially expressed mRNAs were identified based on the screening criteria of |log 2 FC| > 1 and FDR < 0.05. Among these, 132 lncRNAs and 1081 mRNAs were found to be down-regulated, while 172 lncRNAs and 738 mRNAs were up-regulated. GO and KEGG analyses showed that the identified DELs and DEMs were enriched in the entries of pathways associated with muscle growth and development. On this basis, we constructed an lncRNA-mRNA interaction network. Interestingly, two candidate DELs (MSTRG.16260.9 and MSTRG.22127.1) had targeting relationships with 16 (MYC, IGFBP5, IGFBP2, MYH4, FGF6, etc.) genes related to muscle growth and development. These results could provide a basis for further studies on the roles of lncRNAs and mRNAs in muscle growth in Gannan yaks and Jeryak breeds.

Comprehensive Analysis of miRNA and mRNA Expression Profiles during Muscle Development of the Longissimus Dorsi Muscle in Gannan Yaks and Jeryaks.

A hybrid offspring of Gannan yak and Jersey cattle, the Jeryak exhibits apparent hybrid advantages over the Gannan yak in terms of production performance and other factors. The small non-coding RNAs known as miRNAs post-transcriptionally exert a significant regulatory influence on gene expression. However, the regulatory mechanism of miRNA associated with muscle development in Jeryak remains elusive. To elucidate the regulatory role of miRNAs in orchestrating skeletal muscle development in Jeryak, we selected longissimus dorsi muscle tissues from Gannan yak and Jeryak for transcriptome sequencing analysis. A total of 230 (DE) miRNAs were identified in the longissimus dorsi muscle of Gannan yak and Jeryak. The functional enrichment analysis revealed a significant enrichment of target genes from differentially expressed (DE)miRNAs in signaling pathways associated with muscle growth, such as the Ras signaling pathway and the MAPK signaling pathway. The network of interactions between miRNA and mRNA suggest that some (DE)miRNAs, including miR-2478-z, miR-339-x, novel-m0036-3p, and novel-m0037-3p, played a pivotal role in facilitating muscle development. These findings help us to deepen our understanding of the hybrid dominance of Jeryaks and provide a theoretical basis for further research on the regulatory mechanisms of miRNAs associated with Jeryak muscle growth and development.

Wheat powdery mildew resistance: from gene identification to immunity deployment.

Powdery mildew is one of the most devastating diseases on wheat and is caused by the obligate biotrophic phytopathogen Blumeria graminis f. sp. tritici (Bgt). Due to the complexity of the large genome of wheat and its close relatives, the identification of powdery mildew resistance genes had been hampered for a long time until recent progress in large-scale sequencing, genomics, and rapid gene isolation techniques. Here, we describe and summarize the current advances in wheat powdery mildew resistance, emphasizing the most recent discoveries about the identification of genes conferring powdery mildew resistance and the similarity, diversity and molecular function of those genes. Multilayered resistance to powdery mildew in wheat could be used for counteracting Bgt, including durable, broad spectrum but partial resistance, as well as race-specific and mostly complete resistance mediated by nucleotide-binding and leucine rich repeat domain (NLR) proteins. In addition to the above mentioned layers, manipulation of susceptibility (S) and negative regulator genes may represent another layer that can be used for durable and broad-spectrum resistance in wheat. We propose that it is promising to develop effective and durable strategies to combat powdery mildew in wheat by simultaneous deployment of multilayered immunity.

Endoscopic characteristics and high-risk background mucosa factors of early gastric cancer after helicobacter pylori eradication: a single-center retrospective study.

Purpose: Gastric cancer still develops after successful Helicobacter pylori(Hp)eradication. In this study, we aimed to explore the characteristics and risks of mucosal factors. Methods: A total of 139 early gastric cancers (EGC) diagnosed in 133 patients after successful eradication from January 2016 to December 2021 were retrospectively included in the Hp-eradication EGC group and 170 EGCs diagnosed in 158 patients were included in the Hp-positive EGC group. We analyzed the clinical, pathological, and endoscopic characteristics between the two groups to identify the features of EGC after Hp eradication. Another 107 patients with no EGC after Hp eradication were enrolled in a Hp-eradication non-EGC group. The background mucosal factors between the Hp-eradication EGC group and the Hp-eradication non-EGC group were compared to analyze the high-risk background mucosal factors of EGC after eradication. In addition, we divided the EGC group after Hp eradication into IIc type and non-IIc type according to endoscopic gross classification to assess the high-risk background factors of IIc-type EGC after Hp eradication. Results: The endoscopic features of EGC after Hp eradication included location in the lower part of the stomach (p=0.001), yellowish color (p= 0.031), and smaller size (p=0.001). The moderate/severe gastric atrophy (GA), intestinal metaplasia (IM) in the corpus, severe diffuse redness, and map-like redness were risk factors for EGC after eradication (p=0.001, p=0.001, p=0.001, and p= 0.005, respectively). The Kyoto classification total score in the EGC group was higher than the non-EGC group (4 vs.3 p<0.001). A multivariate analysis revealed that depressed erosion (OR=3.42, 95% CI 1.35-8.65, p= 0.009) was an independent risk factor for IIc-type EGC after Hp eradication. Conclusion: EGC after eradication are smaller and yellowish lesions located in the lower part of the stomach. The risk background mucosal factors include moderate/severe GA, IM in the corpus, severe diffuse redness, and map-like redness. The Kyoto classification total score of 4 or more after successful eradication treatment might indicate EGC risk. In addition, the IIc-type EGC should be cautioned in the presence of depressed erosion after Hp eradication.

Evaluation of Atlas-Based Mobile Application in Undergraduate Teaching in Oral Histopathology.

The utilization of mobile devices in education is a growing trend in various subjects. We developed the Dental and Maxillofacial Development Teaching Atlas App, and applied it to the learning process of oral histopathology. The aim of the current study was to investigate the educational effects of atlas-based mobile-assisted teaching in the field of dental medicine, and to suggest relevant improvements. The Dental and Maxillofacial Development Teaching Atlas App encompasses a wide range of atlases. It harbors various features, such as terminology definitions, student communications, and teacher-student interactions. By conducting questionnaires (70 students) and a quiz (68 students), we obtained students' feedback, to evaluate the effects and application prospects of the WeChat applet. The questionnaire results indicate that students experienced a high level of satisfaction and support. Additionally, students participated in the quiz, with the experimental group exhibiting significantly higher average scores than the control group. The fill-in-the-blank questions, image recognition questions, and the total score all demonstrated statistically significant differences, while the terminology definition questions did not. The Dental and Maxillofacial Development Teaching Atlas App facilitates students' utilization of fragmented time for learning, and demonstrates positive effects in enhancing students' learning interests and proactiveness. It also holds promising potential for applications in other disciplines in the field of dental education.

Molecular Mechanisms Behind Vascular Mimicry as the Target for Improved Breast Cancer Management.

Introduction: Breast cancer has a high incidence and mortality rate in women due to metastasis and drug resistance which is associated with vasculogenic mimicry (VM). We purposed to explore VM formulation in breast cancer and mechanism of which is involved in EphA2/PIK3R1/CTNNB1 in the present study. Methods: The expression of EphA2/PIK3R1/CTNNB1 and breast cancer patient prognosis was analyzed from TCGA data, both gene and protein expression as well as VM were measured in human breast cancer tissue samples collected in our study. The relationship between EphA2/PIK3R1/CTNNB1 and the formation of VM in breast cancer and its possible regulatory mechanism was explored. Results: The results of the bioinformatics analysis based on TCGA showed that the expression of PIK3R1/ CTNNB1/ PECAM1 (CD31) in tumor tissues was significantly lower than that in normal tissues. EphA2 was positively correlated with PIK3R1, PIK3R1 with CTNNB1, and CTNNB1 with PECAM1 expression in breast cancer tissues. The results of detection in breast cancer and adjacent tissues indicated that the expression of EphA2/PIK3R1/CTNNB1 in cancer tissues was significantly lower than that in adjacent tissues. The expression of PIK3R1 was positively correlated with EphA2 and CTNNB1 expression, respectively, as well as EphA2 expression correlated with CTNNB1 expression positively. VM formation was significantly increased in breast cancer tissues compared with adjacent tissues. Conclusion: Our results suggested that the formation of VM in breast cancer may be related to the EphA2/PIK3R1/CTNNB1 molecular signaling pathway.

Synthesis and Functions of Resistant Starch.

Resistant starch (RS) has become a popular topic of research in recent years. Most scholars believe that there are 5 types of RS. However, accumulating evidence indicates that in addition to starch-lipid complexes, which are the fifth type of RS, complexes containing starch and other substances can also be generated. The physicochemical properties and physiologic functions of these complexes are worth exploring. New physiologic functions of several original RSs are constantly being discovered. Research shows that RS can provide health improvements in many patients with chronic diseases, including diabetes and obesity, and even has potential benefits for kidney disease and colorectal cancer. Moreover, RS can alter the short-chain fatty acids and microorganisms in the gut, positively regulating the body's internal environment. Despite the increase in its market demand, RS production remains limited. Upscaling RS production is thus an urgent requirement. This paper provides detailed insights into the classification, synthesis, and efficacy of RS, serving as a starting point for the future development and applications of RS based on the current status quo.

A bacterial type III effector targets plant vesicle-associated membrane proteins.

The soilborne bacterial pathogen Ralstonia solanacearum is one of the most destructive plant pathogens worldwide, and its infection process involves the manipulation of numerous plant cellular functions. In this work, we found that the R. solanacearum effector protein RipD partially suppressed different levels of plant immunity triggered by R. solanacearum elicitors, including specific responses triggered by pathogen-associated molecular patterns and secreted effectors. RipD localized in different subcellular compartments in plant cells, including vesicles, and its vesicular localization was enriched in cells undergoing R. solanacearum infection, suggesting that this specific localization may be particularly relevant during infection. Among RipD-interacting proteins, we identified plant vesicle-associated membrane proteins (VAMPs). We also found that overexpression of Arabidopsis thaliana VAMP721 and VAMP722 in Nicotiana benthamiana leaves promoted resistance to R. solanacearum, and this was abolished by the simultaneous expression of RipD, suggesting that RipD targets VAMPs to contribute to R. solanacearum virulence. Among proteins secreted in VAMP721/722-containing vesicles, CCOAOMT1 is an enzyme required for lignin biosynthesis, and mutation of CCOAOMT1 enhanced plant susceptibility to R. solanacearum. Altogether our results reveal the contribution of VAMPs to plant resistance against R. solanacearum and their targeting by a bacterial effector as a pathogen virulence strategy.

Integration of ATAC-Seq and RNA-Seq Analysis to Identify Key Genes in the Longissimus Dorsi Muscle Development of the Tianzhu White Yak.

During the postnatal stages, skeletal muscle development undergoes a series of meticulously regulated alterations in gene expression. However, limited studies have employed chromatin accessibility to unravel the underlying molecular mechanisms governing muscle development in yak species. Therefore, we conducted an analysis of both gene expression levels and chromatin accessibility to comprehensively characterize the dynamic genome-wide chromatin accessibility during muscle growth and development in the Tianzhu white yak, thereby elucidating the features of accessible chromatin regions throughout this process. Initially, we compared the differences in chromatin accessibility between two groups and observed that calves exhibited higher levels of chromatin accessibility compared to adult cattle, particularly within ±2 kb of the transcription start site (TSS). In order to investigate the correlation between alterations in chromatin accessible regions and variations in gene expression levels, we employed a combination of ATAC-seq and RNA-seq techniques, leading to the identification of 18 central transcriptional factors (TFs) and 110 key genes with significant effects. Through further analysis, we successfully identified several TFs, including Sp1, YY1, MyoG, MEF2A and MEF2C, as well as a number of candidate genes (ANKRD2, ANKRD1, BTG2 and LMOD3) which may be closely associated with muscle growth and development. Moreover, we constructed an interactive network program encompassing hub TFs and key genes related to muscle growth and development. This innovative approach provided valuable insights into the molecular mechanism underlying skeletal muscle development in the postnatal stages of Tianzhu white yaks while also establishing a solid theoretical foundation for future research on yak muscle development.

Characteristics and background mucosa status of early gastric cancer after Helicobacter pylori eradication: A narrative review.

Helicobacter pylori (H pylori) eradication treatment can reduce the risk of gastric cancer. However, early gastric cancer (EGC) can still be detected after eradication. Meanwhile, EGC after eradication is challenging to diagnose by an endoscopist in some cases due to the lack of apparent characteristics and the complex mucosal status. This review aims to summarize the endoscopic and histological characteristics and the mucosal risk factors for gastric cancer after H pylori eradication. The literature was searched for possible reported gastric cancer after eradication in "PubMed." These included related clinical studies and reviews, and unrelated or non-English articles were excluded. Endoscopically, EGC displays a small, reddish and depressed lesion, indistinct border, "gastritis-like" appearance and submucosal invasion. Histologically, it is divided into surface differentiation, nontumorous epithelium, and intestinal type. The risk factors include severe gastric atrophy, intestinal metaplasia in the corpus, and map-like redness. In conclusion, these studies on the characteristics and risk mucosal factors of patients with gastric cancer after H pylori eradication will drive the establishment of a novel endoscopic surveillance and diagnosis system for H pylori-eradicated patients.

Protective Actions in Apical Periodontitis: The Regenerative Bioactivities Led by Mesenchymal Stem Cells.

Resulting from bacterial infection, apical periodontitis (AP) is a common inflammatory disease of the periapical region of the tooth. The regeneration of the destroyed periapical alveolar bone and the surrounding periodontium tissues has long been a difficult task in clinical practice. These lesions are closely related to pathogen invasion and an overreactive immune response. It is worth noting that the protective healing process occurs simultaneously, in which mesenchymal stem cells (MSCs) have a crucial function in mediating the immune system and promoting regeneration. Here, we review the recent studies related to AP, with a focus on the regulatory network of MSCs. We also discuss the potential therapeutic approaches of MSCs in inflammatory diseases to provide a basis for promoting tissue regeneration and modulating inflammation in AP. A deeper understanding of the protective action of MSCs and the regulatory networks will help to delineate the underlying mechanisms of AP and pave the way for stem-cell-based regenerative medicine in the future.

Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends.

Pulpal and periapical diseases are the most common dental diseases. The traditional treatment is root canal therapy, which achieves satisfactory therapeutic outcomes-especially for mature permanent teeth. Apexification, pulpotomy, and pulp revascularization are common techniques used for immature permanent teeth to accelerate the development of the root. However, there are obstacles to achieving functional pulp regeneration. Recently, two methods have been proposed based on tissue engineering: stem cell transplantation, and cell homing. One of the goals of functional pulp regeneration is to achieve innervation. Nerves play a vital role in dentin formation, nutrition, sensation, and defense in the pulp. Successful neural regeneration faces tough challenges in both animal studies and clinical trials. Investigation of the regeneration and repair of the nerves in the pulp has become a serious undertaking. In this review, we summarize the current understanding of the key stem cells, signaling molecules, and biomaterials that could promote neural regeneration as part of pulp regeneration. We also discuss the challenges in preclinical or clinical neural regeneration applications to guide deep research in the future.

Sphingomonas sp. Hbc-6 alters physiological metabolism and recruits beneficial rhizosphere bacteria to improve plant growth and drought tolerance.

Drought poses a serious threat to plant growth. Plant growth-promoting bacteria (PGPB) have great potential to improve plant nutrition, yield, and drought tolerance. Sphingomonas is an important microbiota genus that is extensively distributed in the plant or rhizosphere. However, the knowledge of its plant growth-promoting function in dry regions is extremely limited. In this study, we investigated the effects of PGPB Sphingomonas sp. Hbc-6 on maize under normal conditions and drought stress. We found that Hbc-6 increased the biomass of maize under normal conditions and drought stress. For instance, the root fresh weight and shoot dry weight of inoculated maize increased by 39.1% and 34.8% respectively compared with non-inoculated plant, while they increased by 61.3% and 96.3% respectively under drought conditions. Hbc-6 also promoted seed germination, maintained stomatal morphology and increased chlorophyll content so as to enhance photosynthesis of plants. Hbc-6 increased antioxidant enzyme (catalase, superoxide, peroxidase) activities and osmoregulation substances (proline, soluble sugar) and up-regulated the level of beneficial metabolites (resveratrol, etc.). Moreover, Hbc-6 reshaped the maize rhizosphere bacterial community, increased its richness and diversity, and made the rhizosphere bacterial community more complex to resist stress; Hbc-6 could also recruit more potentially rhizosphere beneficial bacteria which might promote plant growth together with Hbc-6 both under normal and drought stress. In short, Hbc-6 increased maize biomass and drought tolerance through the above ways. Our findings lay a foundation for exploring the complex mechanisms of interactions between Sphingomonas and plants, and it is important that Sphingomonas sp. Hbc-6 can be used as a potential biofertilizer in agricultural production, which will assist finding new solutions for improving the growth and yield of crops in arid areas.

The Arabidopsis E3 ubiquitin ligase PUB4 regulates BIK1 and is targeted by a bacterial type-III effector.

Plant immunity is tightly controlled by a complex and dynamic regulatory network, which ensures optimal activation upon detection of potential pathogens. Accordingly, each component of this network is a potential target for manipulation by pathogens. Here, we report that RipAC, a type III-secreted effector from the bacterial pathogen Ralstonia solanacearum, targets the plant E3 ubiquitin ligase PUB4 to inhibit pattern-triggered immunity (PTI). PUB4 plays a positive role in PTI by regulating the homeostasis of the central immune kinase BIK1. Before PAMP perception, PUB4 promotes the degradation of non-activated BIK1, while after PAMP perception, PUB4 contributes to the accumulation of activated BIK1. RipAC leads to BIK1 degradation, which correlates with its PTI-inhibitory activity. RipAC causes a reduction in pathogen-associated molecular pattern (PAMP)-induced PUB4 accumulation and phosphorylation. Our results shed light on the role played by PUB4 in immune regulation, and illustrate an indirect targeting of the immune signalling hub BIK1 by a bacterial effector.