Functional screening of the Arabidopsis 2C protein phosphatases family identifies PP2C15 as a negative regulator of plant immunity by targeting BRI1-associated receptor kinase 1.

Genetic engineering using negative regulators of plant immunity has the potential to provide a huge impetus in agricultural biotechnology to achieve a higher degree of disease resistance without reducing yield. Type 2C protein phosphatases (PP2Cs) represent the largest group of protein phosphatases in plants, with a high potential for negative regulatory functions by blocking the transmission of defence signals through dephosphorylation. Here, we established a PP2C functional protoplast screen using pFRK1::luciferase as a reporter and found that 14 of 56 PP2Cs significantly inhibited the immune response induced by flg22. To verify the reliability of the system, a previously reported MAPK3/4/6-interacting protein phosphatase, PP2C5, was used; it was confirmed to be a negative regulator of PAMP-triggered immunity (PTI). We further identified PP2C15 as an interacting partner of BRI1-associated receptor kinase 1 (BAK1), which is the most well-known co-receptor of plasma membrane-localized pattern recognition receptors (PRRs), and a central component of PTI. PP2C15 dephosphorylates BAK1 and negatively regulates BAK1-mediated PTI responses such as MAPK3/4/6 activation, defence gene expression, reactive oxygen species bursts, stomatal immunity, callose deposition, and pathogen resistance. Although plant growth and 1000-seed weight of pp2c15 mutants were reduced compared to those of wild-type plants, pp2c5 mutants did not show any adverse effects. Thus, our findings strengthen the understanding of the mechanism by which PP2C family members negatively regulate plant immunity at multiple levels and indicate a possible approach to enhance plant resistance by eliminating specific PP2Cs without affecting plant growth and yield.

Palliative primary tumor resection may not offer survival benefits for patients with unresectable metastatic colorectal neuroendocrine neoplasms, one multicenter retrospective cohort study.

BACKGROUND: The efficacy of palliative primary tumor resection (PTR) in improving prognosis for patients with unresectable metastatic colorectal neuroendocrine neoplasms (NENs) has not been fully explored. METHODS: We performed one retrospective cohort study and recruited 68 patients with unresectable metastatic colorectal NENs from two Chinese medical centers between 2000 and 2022. All patients were assigned to PTR group and no PTR group. The clinicopathological manifestation data were carefully collected, and the survival outcomes were compared between the two groups using Kaplan-Meier methods. Propensity score matching (PSM) was conducted to minimize confounding bias. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: A total of 32 patients received PTR, and the other 36 patients did not. The median progression-free survival (PFS) and overall survival (OS) times were 4 and 22 months in the whole cohort, respectively. For patients who received no PTR, the median OS was 16 months, and the 1-year OS rate and 3-year OS rate were 56.4% and 39.6%, respectively. For patients who received PTR, the median OS was 24 months, and the 1-year OS rate and 3-year OS rate were 67.9% and 34.1%, respectively. However, the Kaplan-Meier survival curves and log-rank test demonstrated no significant survival difference between the two groups (P = 0.963). Moreover, palliative PTR was also not confirmed as a prognostic factor in subsequent univariable and multivariable Cox proportional hazards regression analyses in both the original and matched cohorts. Only histological differentiation was identified as an independent prognostic factor affecting PFS [hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.02-3.41, P = 0.043] and OS [HR = 3.70, 95% CI: 1.09-12.48, P = 0.035] in the original cohort. CONCLUSIONS: Palliative PTR may not offer survival benefits for patients with unresectable metastatic colorectal NENs.

Coevolution between heat and cold tolerance in endotherms.

Whether the heat and cold tolerance of endotherms evolve independently or correlatively remains unresolved. Both physiological trade-offs and natural selection can contribute to a coevolutionary pattern of heat and cold tolerance in endotherms. Using a published database, we tested the correlation between upper and lower thermal limits across endothermic species with multi-response generalized linear mixed models incorporating phylogenies. We found a positive correlation between upper and lower thermal limits, which suggested a coevolutionary pattern of heat and cold tolerance. Specifically, this relationship between heat and cold tolerance is phylogenetically constrained for tropical endotherms but not for temperate endotherms. The correlated evolution between heat and cold tolerance may have a significant influence on endotherms' evolution and ecology and needs to be further investigated.

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model.

BACKGROUND: Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options. Recombinant adeno-associated virus (rAAV) provides a promising platform for gene therapy on such kinds of diseases. A microRNA (miRNA) let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated. AIM: To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8 (rAAV8) on a xenobiotic-induced mouse model of sclerosing cholangitis. METHODS: A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine (DDC) feeding for 2 wk or 6 wk. A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding. Upon sacrifice, the liver and the serum were collected from each mouse. The hepatobiliary injuries, hepatic inflammation and fibrosis were evaluated. The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot. RESULTS: rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk. The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers, and prevent the proliferation of cholangiocytes and biliary fibrosis. Furthermore, inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1, which consequently inhibit of NF-κB-mediated hepatic inflammation. CONCLUSION: Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis, which provides a possible clinical translation of PSC of human.

Application of antimicrobial peptides in plant protection: making use of the overlooked merits.

Pathogen infection is one of the major causes of yield loss in the crop field. The rapid increase of antimicrobial resistance in plant pathogens has urged researchers to develop both new pesticides and management strategies for plant protection. The antimicrobial peptides (AMPs) showed potential on eliminating plant pathogenic fungi and bacteria. Here, we first summarize several overlooked advantages and merits of AMPs, which includes the steep dose-response relations, fast killing ability, broad synergism, slow resistance selection. We then discuss the possible application of AMPs for plant protection with above merits, and highlight how AMPs can be incorporated into a more efficient integrated management system that both increases the crop yield and reduce resistance evolution of pathogens.

Arabidopsis Protein Phosphatase PIA1 Impairs Plant Drought Tolerance by Serving as a Common Negative Regulator in ABA Signaling Pathway.

Reversible phosphorylation of proteins is a ubiquitous regulatory mechanism in vivo that can respond to external changes, and plays an extremely important role in cell signal transduction. Protein phosphatase 2C is the largest protein phosphatase family in higher plants. Recently, it has been found that some clade A members can negatively regulate ABA signaling pathways. However, the functions of several subgroups of Arabidopsis PP2C other than clade A have not been reported, and whether other members of the PP2C family also participate in the regulation of ABA signaling pathways remains to be studied. In this study, based on the previous screening and identification work of PP2C involved in the ABA pathway, the clade F member PIA1 encoding a gene of the PP2C family, which was down-regulated after ABA treatment during the screening, was selected as the target. Overexpression of PIA1 significantly down-regulated the expression of ABA marker gene RD29A in Arabidopsis protoplasts, and ABA-responsive elements have been found in the cis-regulatory elements of PIA1 by promoter analysis. When compared to Col-0, transgenic plants overexpressing PIA1 were less sensitive to ABA, whereas pia1 showed the opposite trait in seed germination, root growth, and stomatal opening experiments. Under drought stress, SOD, POD, CAT, and APX activities of PIA1 overexpression lines were lower than Col-0 and pia1, while the content of H2O2 was higher, leading to its lowest survival rate in test plants, which were consistent with the significant inhibition of the expression of ABA-dependent stress-responsive genes RD29B, ABI5, ABF3, and ABF4 in the PIA1 transgenic background after ABA treatment. Using yeast two-hybrid and luciferase complementation assays, PIA1 was found to interact with multiple ABA key signaling elements, including 2 RCARs and 6 SnRK2s. Our results indicate that PIA1 may reduce plant drought tolerance by functioning as a common negative regulator involved in ABA signaling pathway.

Genetic variation and population structure of a widely distributed damselfly (Ischnura senegalensis).

Ischnura senegalensis Rambur, 1842 is among the most widespread damselfly species in the world. Unlike dragonflies with strong migration abilities, I. senegalensis have limited dispersing abilities. Gene flow among I. senegalensis populations may be greatly influenced by anthropogenic disturbance, fragmented suitable habitats, sea straits, or even global warming. In this study, to investigate the genetic diversity of I. senegalensis populations, we sequenced and collected 498 cytochrome oxidase I sequences across the Old World. Haplotype network analysis showed 51 haplotypes and I. senegalensis could be grouped into four regions (Afrotropical region, Oriental region, main Islands of Japan, and the Ryukyu Islands), each of which contains different dominant haplotypes. Based on molecular variance analysis, we found that populations from the Afrotropical region have quite a low gene flow with the Asian populations (except Yemen). Furthermore, rice cultivation may aid the dispersion of I. senegalensis in the oriental region. Populations from the Ryukyu Islands show the highest genetic diversity, which may be due to the geological separation among islands. Our results prove that I. senegalensis has great genetic diversity among different populations across the world.

Conservation and divergence of flg22, pep1 and nlp20 in activation of immune response and inhibition of root development.

Many pattern-recognition receptors (PRRs) and their corresponding ligands have been identified. However, it is largely unknown how similar and different these ligands are in inducing plant innate immunity and affecting plant development. In this study, we examined three well characterized ligands in Arabidopsis thaliana, namely flagellin 22 (flg22), plant elicitor peptide 1 (pep1) and a conserved 20-amino-acid fragment found in most necrosis and ethylene-inducing peptide 1-like proteins (nlp20). Our quantitative analyses detected the differences in amplitude in the early immune responses of these ligands, with nlp20-induced responses typically being slower than those mediated by flg22 and pep1. RNA sequencing showed the shared differentially expressed genes (DEGs) was mostly enriched in defense response, whereas nlp20-regulated genes represent only a fraction of those genes differentially regulated by flg22 and pep1. The three elicitors all inhibited primary root growth, especially pep1, which inhibited both auxin transport and signaling pathway. In addition, pep1 significantly inhibited the cell division and genes involved in cell cycle. Compared with flg22 and nlp20, pep1 induced much stronger expression of its receptor in roots, suggesting a potential positive feedback regulation in the activation of immune response. Despite PRRs and their co-receptor BAK1 were necessary for both PAMP induced immune response and root growth inhibition, bik1 mutant only showed impaired defense response but relatively normal root growth inhibition, suggesting BIK1 acts differently in these two biological processes.

Mechanic Insight into the Distinct and Common Roles of Ovariectomy Versus Adrenalectomy on Adipose Tissue Remodeling in Female Mice.

Dysfunctions of the ovaries and adrenal glands are both evidenced to cause aberrant adipose tissue (AT) remodeling and resultant metabolic disorders, but their distinct and common roles are poorly understood. In this study, through biochemical, histological and RNA-seq analyses, we comprehensively explored the mechanisms underpinning subcutaneous (SAT) and visceral adipose tissue (VAT) remodeling, in response to ovariectomy (OVX) versus adrenalectomy (ADX) in female mice. OVX promoted adipocyte differentiation and fat accumulation in both SAT and VAT, by potentiating the Pparg signaling, while ADX universally prevented the cell proliferation and extracellular matrix organization in both SAT and VAT, likely by inactivating the Nr3c1 signaling, thus causing lipoatrophy in females. ADX, but not OVX, exerted great effects on the intrinsic difference between SAT and VAT. Specifically, ADX reversed a large cluster of genes differentially expressed between SAT and VAT, by activating 12 key transcription factors, and thereby caused senescent cell accumulation, massive B cell infiltration and the development of selective inflammatory response in SAT. Commonly, both OVX and ADX enhance circadian rhythmicity in VAT, and impair cell proliferation, neurogenesis, tissue morphogenesis, as well as extracellular matrix organization in SAT, thus causing dysfunction of adipose tissues and concomitant metabolic disorders.

UNC93B1 facilitates TLR18-mediated NF-κB signal activation in Schizothorax prenanti.

Toll-like receptor 18 (TLR18), a non-mammalian TLR, has been believed to play an important role in anti-bacterial immunity of teleost fishes. UNC93B1 is a classical molecular chaperone that mediates TLRs transport from endoplasmic reticulum to the located membrane. However, TLR18-mediated signal transduction mechanism and the regulatory effect of UNC93B1 to TLR18 are still unclear in teleost fishes. In this study, the coding sequences of TLR18 and UNC93B1 were cloned from Schizothorax prenanti, named spTLR18 and spUNC93B1, respectively. The spTLR18 and spUNC93B1 are 2583 bp and 1878 bp in length, encode 860 and 625 amino acids, respectively. The spTLR18 widely expressed in various tissues with the highest expression level in liver. After stimulation of Aeromonas hydrophila, lipopolysaccharide (LPS) and Poly(I:C), the expression levels of spTLR18 were significantly increased in spleen and head kidney. The spTLR18 located in the cell membrane, while spUNC93B1 located in the cytoplasm. Luciferase and overexpression analysis showed that spTLR18 activated NF-κB and type I IFN signal pathways, and spTLR18-mediated NF-κB activation might depend on the adaptor molecule MyD88. Besides, spUNC93B1 positively regulates spTLR18-mediated NF-κB signal. Our study first uncovers TLR18-UNC93B1-mediated signal transduction mechanism, which contributes to the understanding of TLR signaling pathway in teleost fishes.

A retrospective analysis of 32 small and well-differentiated rectal neuroendocrine tumors with regional or distant metastasis.

Rectal neuroendocrine neoplasms (NENs) are a group of rare and heterogeneous diseases and are classified as well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on histological differentiation. The patients were followed up with a median period of 32.5 (range 2-123) months and no patients were lost to follow-up. The median PFS time could not be obtained, as only less than half of the patients suffered tumor progression by the end of follow-up. The 1-year and 3-year PFS rates were 73.5% and 69.2%, respectively. The median OS was 86 months in the entire cohort. The 1-year and 3-year OS rates were 100% and 96.0%, respectively.

Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2.

Clonorchis sinensis (C. sinensis) infection induces severe hepatobiliary injuries, which can cause inflammation, periductal fibrosis, and even cholangiocarcinoma. Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) and its receptor S1P receptors (S1PRs) have been implicated in many liver-related diseases. However, the role of S1PRs in C. sinensis-mediated biliary epithelial cells (BECs) proliferation and hepatobiliary injury has not been elucidated. In the present study, we found that C. sinensis infection resulted in alteration of bioactive lipids and sphingolipid metabolic pathways in mice liver. Furthermore, S1PR2 was predominantly activated among these S1PRs in BECs both in vivo and in vitro. Using JTE-013, a specific antagonist of S1PR2, we found that the hepatobiliary pathological injuries, inflammation, bile duct hyperplasia, and periductal fibrosis can be significantly inhibited in C. sinensis-infected mice. In addition, both C. sinensis excretory-secretory products (CsESPs)- and S1P-induced activation of AKT and ERK1/2 were inhibited by JTE-013 in BECs. Therefore, the sphingolipid metabolism pathway and S1PR2 play an important role, and may serve as potential therapeutic targets in hepatobiliary injury caused by C. sinensis-infection.

IL-10 regulates Th17 response to inhibit hepatobiliary injury caused by Clonorchis sinensis infection in C57BL/6J mice.

Clonorchiasis caused by Clonorchis sinensis is a mainly foodborne parasitic disease. It can lead to hepatobiliary duct inflammation, fibrosis, obstructive jaundice, liver cirrhosis, and even cholangiocarcinoma. Interleukin (IL)-10 is an immune-regulatory cytokine which plays an immunosuppressive role during infection. Our previous study found that IL-10 was increased in mice with C. sinensis infection. However, the role and mechanism of IL-10 playing in hepatobiliary injury induced by C. sinensis infection remain unknown. Herein, Il10+/+ mice and Il10+/- C57BL/6J mice were infected with C. sinensis. It was found that IL-10 deficiency aggravated biliary hyperplasia and exacerbated periductal fibrosis induced by C. sinensis infection. Moreover, IL-10 deficiency increased CD4+T cells and CD8+T cells but not macrophages in the liver of mice with infection. There were no apparent differences in Th1 and Treg cells between Il10+/+ and Il10+/- mice infected with C. sinensis. However, the proportion of Th17 cells in CD4+T cells in Il10+/- infected mice was significantly higher than that in Il10+/+ infected mice. IL-10 deficiency also enhanced the increase of Th17 cells induced by ESPs stimulation in vitro. Taken together, our results suggest that IL-10 plays a protective role in hepatobiliary injury in C57BL/6J mice induced by C. sinensis infection via inhibiting Th17 cells, which could deepen our understanding of the immunopathology of clonorchiasis.

The Evolution of Glycoside Hydrolase Family 1 in Insects Related to Their Adaptation to Plant Utilization.

Insects closely interact with plants with multiple genes involved in their interactions. ß-glucosidase, constituted mainly by glycoside hydrolase family 1 (GH1), is a crucial enzyme in insects to digest plant cell walls and defend against natural enemies with sequestered plant metabolites. To gain more insights into the role of this enzyme in plant-insect interactions, we analyzed the evolutionary history of the GH1 gene family with publicly available insect genomes. We found that GH1 is widely present in insects, while the gene numbers are significantly higher in insect herbivores directly feeding on plant cell walls than in other insects. After reconciling the insect GH1 gene tree with a species tree, we found that the patterns of duplication and loss of GH1 genes differ among insect orders, which may be associated with the evolution of their ecology. Furthermore, the majority of insects' GH1 genes were tandem-duplicated and subsequently went through neofunctionalization. This study shows the evolutionary history of an important gene family GH1 in insects and facilitates our understanding of the evolution of insect-plant interactions.

Effects of active immunization against a 13-amino acid receptor-binding epitope of FSHß on fertility regulation in female mice.

Follicle-stimulating hormone (FSH) is crucial for ovarian folliculogenesis and thus essential for female fertility. Here, we developed a novel FSH vaccine based on the tandem of a 13-amino acid receptor-binding epitope of FSHß (FSHß13AA-T) and used a mouse model to test its efficacy in female fertility regulation. Compared to placebo-immunized controls, FSHß13AA-T vaccination: induced a marked (P < 0.05) antibody generation; reduced (P < 0.05) serum concentrations of FSH, inhibin B and 17ß-estradiol; disrupted (P < 0.05) normal estrous cyclicity; delayed (P = 0.08) establishment of pregnancy; blocked (P < 0.05) folliculogenesis; and reduced (P < 0.05) litter size. Mechanistically, FSH vaccination reduced (P < 0.05) ovarian estrogen production by decreasing Lhcgr, Cyp19a1 and HSD3ß1 expression, and suppressed ovarian follicular development by decreasing ovarian Fshr, Inhα, Foxo3a, Bmp15 and Cdh1 expression. Overall, vaccination of female mice with FSHß13AA-T substantially disrupted FSH-dependent ovarian steroidogenesis and folliculogenesis, and caused subfertility. Therefore, vaccines based on FSHß13AA-T have potential as anti-fertility/contraceptive agents in females.

Prevalence and new genotypes of Enterocytozoon bieneusi in wild rhesus macaque (Macaca mulatta) in China: A zoonotic concern.

Enterocytozoon bieneusi is a zoonotic pathogen with a wide range of animal host. There are only few reports of E. bieneusi infection in wild Chinese rhesus macaques. Here, we determined the prevalence of E. bieneusi in nine wild rhesus macaque populations and assessed their zoonotic potential by performed genotype of ITS gene. A total of 324 fecal samples of rhesus macaque were collected in nine geographical populations from five Chinese provinces (Sichuan, Chongqing, Qinghai, Tibet and Hainan). 38 samples (11.7%) were found to be infected with E. bieneusi, and 11 genotypes were identified including three known genotypes (D, EbpC and SCC-2) and eight novel genotypes named Mul6∼13. Genotype D (63.2%) was the most prevalent, being observed in seven populations except XZ-2 and QH, and other genotypes were identified only in a single area. According to the phylogenetic analysis, Mul6∼9, Mul11∼13 and zoonotic genotype D were clustered into Group 1, indicating that these genotypes may be potentially zoonotic. Among nine populations, population SC-3 had the highest infection rate (26.3%), and the lowest was the wild QH population without infection, but the difference of infection rate among the nine populations is not significant. It is concluded that, rhesus macaque populations are generally infected E. bieneusi in many areas of China, and there may be a risk of cross infection with E. bieneusi in some areas found having zoonotic genotypes, and these areas should be paid more attention to prevent.

RNA-seq coupling two different methods of castration reveals new insights into androgen deficiency-caused degeneration of submaxillary gland in male Sprague Dawley rats.

BACKGROUND: Salivary gland (SMG) degeneration and dysfunction are common symptoms that occur after sex hormone deprivation, but the underlying mechanisms remain largely unknown. Additionally, immunocastration, which causes drop of sex hormones, has been developed as an alternative to surgical castration, however whether it exerts similar effects as surgical castration on the salivary glands is unknown. Through histological and RNA-seq analysis, we assessed changes in morphology and transcriptome of SMG in response to immunocastration (IM) versus surgical castration (bilateral orchiectomy, ORC). RESULTS: Compared to entire males (EM), ORC caused severe degeneration of SMG in rats, as evidenced by both decreased (P < 0.01) SMG weight and organ index, and by decreased (P < 0.01) quantity of SMG acini and ducts. IM had minimal effects (P > 0.05) on SMG weight and organ index, but it still caused degeneration (P < 0.05) of the acini and ducts. Even though, the quantity of both SMG acini and ducts was much higher (P < 0.001) in IM than in ORC. Functional enrichment analysis of the common regulated genes by ORC/IM revealed disrupted epithelial cell development, angiogenesis, anatomical structure morphogenesis and enhanced cell death are associated with SMG degeneration in deprivation of androgens. Integrated data analysis shown that there existed a selective hyperfunction of SMG ribosome and mitochondrion in ORC but not in IM, which might be associated with more severe degeneration of SMG in ORC than in IM. CONCLUSIONS: Our findings suggested that both surgical castration and immunocastration caused SMG degeneration by disrupting epithelial cell development, angiogenesis, anatomical structure morphogenesis and enhancing cell death. But, surgical castration selectively induced hyperfunction of SMG ribosome and mitochondrion, thus causing more severe degeneration of SMG than immunocastration.

Complete mitochondrial genomes of two damselfly species in coenagrionidae and phylogenetic implications.

Agriocnemis femina (Brauer, 1868) and Ischnura senegalensis (Rambur, 1842) are two damselflies inhabiting paddy lands. As an intermediate predator, they play an important role in controlling certain crop pest and mosquitoes. In this study, we sequenced complete mitogenomes of these two species. The total length of mitogenomes is 15,936 bp in A. femina and 15,762 bp in I. senegalensis. Both of mitogenomes consist of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region. The close relationship between I. senegalensis and I. elegans was further proved by phylogenetic analysis. Our phylogenetic analysis indicated a clear two lineages in Coenagrionidae (Core and ridge-faced Coenagrionidae). Ridge-faced Coenagrionidae consisted of Megaloprepus caerulatus and Ceriagrion fallax. In core Coenagrionidae, Ischnura and Enallagma are most closely related; they formed one clade with Agriocnemis and then grouped together with Paracerion. Our study provides new genetic information for further study in phylogenetic analysis of Coenagrionidae.

Identification and functional analysis of NOD2 and its two splicing variants associated with a novel pattern of signal regulation in teleost fishes.

The nucleotide-binding oligomerization domain 2 (NOD2) has been identified as an important sensor for microorganic invasion in both mammals and teleost fishes. In this study, two splicing variants of NOD2 (NOD2-v1 and NOD2-v2) were identified as truncating the functional domains of wild-type NOD2 in the teleost fish Schizothorax prenanti. NOD2-v1 included an intron sequence that terminated within the third leucine-rich repeat (LRR) domain, while NOD2-v2 incorporated an insertion of one and half intron sequences and truncated within the second caspase activation and recruitment domain (CARD). NOD2, NOD2-v1 and NOD2-v2 genes were ubiquitously expressed. All three genes positively responded to exposure of Aeromonas hydrophila and lipopolysaccharide stimulation in varying degrees. Using luciferase activity assays in HEK293T cells, our results revealed that NOD2 activated the NF-κB signal and recognized muramyl dipeptide (MDP). NOD2-v1 exhibited deficiency in the LRR domains and could not sense MDP, but maintained the ability to activate NF-κB and enhanced NOD2-mediated MDP recognition. Given the significant change to the functional structure, NOD2-v2 lost its capacity for NF-κB activation, but interestingly repressed NOD2-mediated MDP sensing and NF-κB activation, and even NOD2-v1-induced NF-κB activation. Altogether, our study reveals a novel pattern of signal regulation by splicing variants in teleost fishes.