Two cytokine receptor family B (CRFB) members in orange-spotted grouper Epinephelus coioides, EcCRFB3 and EcCRFB4, negatively regulate interferon immune responses to assist nervous necrosis virus replication.

Receptors of type I interferon (IFNR) play a vital role in the antiviral immune response. However, little is known about the negative regulatory role of the IFNR. Nervous necrosis virus (NNV) is one of the most significant viruses in cultured fish, resulting in great economic losses for the aquaculture industry. In this study, two orange-spotted grouper (Epinephelus coioides) cytokine receptor family B (CRFB) members, EcCRFB3 and EcCRFB4 were cloned and characterized from NNV infected grouper brain (GB) cells. The open reading frame (ORF) of EcCRFB3 consists of 852 bp encoding 283 amino acids, while EcCRFB4 has an ORF of 990 bp encoding 329 amino acids. The mRNA levels of EcCRFB3 or EcCRFB4 were significantly upregulated after NNV infection and the stimulation of poly (I:C) or NNV-encoded Protein A. In addition, EcCRFB3 or EcCRFB4 overexpression facilitated NNV replication, whereas EcCRFB3 or EcCRFB4 silencing resisted NNV replication. Overexpressed EcCRFB3 or EcCRFB4 inhibited the expression of IFN-I-induced ISGs. Taken together, our research provides the first evidence in fish demonstrating the role of IFNRs to regulate the IFN signaling pathway negatively. Our findings enrich the understanding of the functions of IFNRs and reveal a novel escape mechanism of NNV.

Nervous necrosis virus capsid protein and Protein A dynamically modulate the fish cGAS-mediated IFN signal pathway to facilitate viral evasion.

Nervous necrosis virus (NNV), an aquatic RNA virus belonging to Betanodavirus, infects a variety of marine and freshwater fishes, leading to massive mortality of cultured larvae and juveniles and substantial economic losses. The enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is widely recognized as a central component in the innate immune response to cytosolic DNA derived from different pathogens. However, little is known about the response of cGAS to aquatic RNA viruses. This study found that Epinephelus coioides cGAS (EccGAS) overexpression inhibited NNV replication, whereas EccGAS silencing promoted NNV replication. The anti-NNV activity of EccGAS was involved in interferon (IFN) signaling activation including tumor necrosis factor receptor-associated factor family member-associated NF-kappa-B activator-binding kinase 1 (TBK1) phosphorylation, interferon regulatory factor 3 (IRF3) nuclear translocation, and the subsequent induction of IFNc and ISGs. Interestingly, NNV employed its capsid protein (CP) or Protein A (ProA) to negatively or positively modulate EccGAS-mediated IFN signaling by simultaneously targeting EccGAS. CP interacted with EccGAS via the arm-P, S-P, and SD structural domains and promoted its polyubiquitination with K48 and K63 linkages in an EcUBE3C (the ubiquitin ligase)-dependent manner, ultimately leading to EccGAS degradation. Conversely, ProA bound to EccGAS and inhibited its ubiquitination and degradation. In regulating EccGAS protein content, CP's inhibitory action was more pronounced than ProA's protective effect, allowing successful NNV replication. These novel findings suggest that NNV CP and ProA dynamically modulate the EccGAS-mediated IFN signaling pathway to facilitate the immune escape of NNV. Our findings shed light on a novel mechanism of virus-host interaction and provide a theoretical basis for the prevention and control of NNV.IMPORTANCEAs a well-known DNA sensor, cGAS is a pivotal component in innate anti-viral immunity to anti-DNA viruses. Although there is growing evidence regarding the function of cGAS in the resistance to RNA viruses, the mechanisms by which cGAS participates in RNA virus-induced immune responses in fish and how aquatic viruses evade cGAS-mediated immune surveillance remain elusive. Here, we investigated the detailed mechanism by which EccGAS positively regulates the anti-NNV response. Furthermore, NNV CP and ProA interacted with EccGAS, regulating its protein levels through ubiquitin-proteasome pathways, to dynamically modulate the EccGAS-mediated IFN signaling pathway and facilitate viral evasion. Notably, NNV CP was identified to promote the ubiquitination of EccGAS via ubiquitin ligase EcUBE3C. These findings unveil a novel strategy for aquatic RNA viruses to evade cGAS-mediated innate immunity, enhancing our understanding of virus-host interactions.

The intestine microbiota of shrimp and its impact on cultivation.

Intestinal microbiome contains several times of functional genes compared to the host and mediates the generation of multiple metabolic products, and therefore it is called "second genome" for host. Crustaceans rank second among the largest subphylum of aquaculture animals that are considered potentially satisfy global substantial food and nutrition security, among which the Pacific white shrimp (Litopenaeus vannamei) ranks the first in the production. Currently, increasing evidences show that outbreaks of some most devastating diseases in shrimp, including white feces syndrome (WFS) and acute hepatopancreatic necrosis disease (AHPND), are related to intestinal microbiota dysbiosis. Importantly, the intestine microbial composition can be altered by environmental stress, diet, and age. In this review, we overview the progress of intestinal microbiota dysbiosis and WFS or ANPHD in shrimp, and how the microbial composition is altered by external factors. Hence, developing suitable microbial micro-ecological prevention and control strategy to maintain intestinal balance may be a feasible solution to reduce the risk of disease outbreaks. Moreover, we highlight that defining the "healthy intestine microbiota" and evaluating the causality of intestinal microbiota dysbiosis and diseases following the logic of "Microecological Koch's postulates" should be the key goal in future shrimp intestinal field, which help to guide disease diagnosis and prevent disease outbreaks in shrimp farming. KEY POINTS: • Intestinal microbiota dysbiosis is relevant to multiple shrimp diseases. • Microecological Koch's postulates help to evaluate the causality of shrimp diseases.

A Negative Regulatory Feedback Loop within the JAK-STAT Pathway Mediated by the Protein Tyrosine Phosphatase DUSP14 in Shrimp.

The JAK-STAT pathway is a central communication node for various biological processes. Its activation is characterized by phosphorylation and nuclear translocation of the transcription factor STAT. The regulatory balance of JAK-STAT signaling is important for maintenance of immune homeostasis. Protein tyrosine phosphatases (PTPs) induce dephosphorylation of tyrosine residues in intracellular proteins and generally function as negative regulators in cell signaling. However, the roles of PTPs in JAK-STAT signaling, especially in invertebrates, remain largely unknown. Pacific white shrimp Penaeus vannamei is currently an important model for studying invertebrate immunity. This study identified a novel member of the dual-specificity phosphatase (DUSP) subclass of the PTP superfamily in P. vannamei, named PvDUSP14. By interacting with and dephosphorylating STAT, PvDUSP14 inhibits the excessive activation of the JAK-STAT pathway, and silencing of PvDUSP14 significantly enhances humoral and cellular immunity in shrimp. The promoter of PvDUSP14 contains a STAT-binding motif and can be directly activated by STAT, suggesting that PvDUSP14 is a regulatory target gene of the JAK-STAT pathway and mediates a negative feedback regulatory loop. This feedback loop plays a role in maintaining homeostasis of JAK-STAT signaling and is involved in antibacterial and antiviral immune responses in shrimp. Therefore, the current study revealed a novel inhibitory mechanism of JAK-STAT signaling, which is of significance for studying the regulatory mechanisms of immune homeostasis in invertebrates.

Changes of bacterial communities and bile acid metabolism reveal the potential "intestine-hepatopancreas axis" in shrimp.

The interaction between the gut and the liver plays a significant role in individual health and diseases. Mounting evidence supports that bile acids are important metabolites in the bidirectional communication between the gut and the liver. Most of the current studies on the "gut-liver axis" have focused on higher vertebrates, however, few was reported on lower invertebrates such as shrimp with an open circulatory system. Here, microbiomic and metabolomic analyses were conducted to investigate the bacterial composition and bile acid metabolism in intestine, hemolymph and hepatopancreas of Penaeus vannamei fed diets supplemented with octanoic acid and oleic acid. After six days of feeding, the bacterial composition in intestine, hemolymph and hepatopancreas changed at different stages, with significant increases in the relative abundance of several genera such as Pseudomonas and Rheinheimera in intestine and hepatopancreas. Notably, there was a more similar bacterial composition in intestine and hepatopancreas at the genus level, which indicated the close communication between shrimp intestine and hepatopancreas. Meanwhile, higher content of some bile acids such as lithocholic acid (LCA) and α-muricholic acid (α-MCA) in intestine and lower content of some bile acids such as taurohyocholic acids (THCA) and isolithocholic acid (IsoLCA) in hepatopancreas were detected. Furthermore, Spearman correlation analysis revealed a significant correlation between bacterial composition and bile acid metabolism in intestine and hepatopancreas. The microbial source tracking analysis showed that there was a high proportion of intestine and hepatopancreas bacterial community as the source of each other. Collectively, these results showed a strong crosstalk between shrimp intestine and hepatopancreas, which suggests a unique potential "intestine-hepatopancreas axis" in lower invertebrate shrimp with an open circulatory system. Our finding contributed to the understanding of the interplay between shrimp intestine and hepatopancreas in the view of microecology and provided new ideas for shrimp farming and disease control.

Nucleic Acid Sensing by STING Induces an IFN-like Antiviral Response in a Marine Invertebrate.

The cytosolic detection of pathogen-derived nucleic acids has evolved as an essential strategy for host innate immune defense in mammals. One crucial component in this process is the stimulator of IFN genes (STING), which acts as a vital signaling adaptor, connecting the cytosolic detection of DNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) to the downstream type I IFN signaling pathway. However, this process remains elusive in invertebrates. In this study, we present evidence demonstrating that STING, an ortholog found in a marine invertebrate (shrimp) called Litopenaeus vannamei, can directly detect DNA and initiate an IFN-like antiviral response. Unlike its homologs in other eukaryotic organisms, which exclusively function as sensors for cyclic dinucleotides, shrimp STING has the ability to bind to both double-stranded DNA and cyclic dinucleotides, including 2'3'-cGAMP. In vivo, shrimp STING can directly sense DNA nucleic acids from an infected virus, accelerate IFN regulatory factor dimerization and nuclear translocation, induce the expression of an IFN functional analog protein (Vago4), and finally establish an antiviral state. Taken together, our findings unveil a novel double-stranded DNA-STING-IKKε-IRF-Vago antiviral axis in an arthropod, providing valuable insights into the functional origins of DNA-sensing pathways in evolution.

Study on the Effect of Microstructure and Inclusions on Corrosion Resistance of Low-N 25Cr-Type Duplex Stainless Steel via Additive Manufacturing.

Duplex stainless steels are widely used in many fields due to their excellent corrosion resistance and mechanical properties. However, it is a challenge to achieve duplex microstructure and excellent properties through additive manufacturing. In this work, a 0.09% N 25Cr-type duplex stainless steel was prepared by additive manufacturing (AM) and heat treatment, and its corrosion resistance was investigated. The results show that, compared with S32750 duplex stainless steel prepared by a conventional process, the combination value of film resistance and charge transfer resistance of AM duplex stainless steel was increased by 3.2-5.5 times and the pitting potential was increased by more than 100 mV. The disappearance of residual thermal stress and the reasonable distribution of Cr and N elements in the two phases are the reasons for the improvement of the corrosion resistance of AM duplex stainless steel after heat treatment. In addition, the extremely high purity of AM duplex stainless steel with no visible inclusions resulted in a higher corrosion resistance exhibited at lower pitting-resistance-equivalent number values.

Molecular mechanism of infectious spleen and kidney necrosis virus in manipulating the hypoxia-inducible factor pathway to augment virus replication.

Infectious spleen and kidney necrosis virus (ISKNV), a member of the genus Megalocytivirus in the family Iridoviridae, can infect over 50 fish species and cause significant economic losses in Asia. Our previous study showed that hypoxia triggers the hypoxia-inducible factor pathway (HIF-pathway), leading to increased replication of ISKNV through promoting the upregulation of viral hypoxic response genes like orf077r. This study delved into the molecular mechanism of how ISKNV manipulates the HIF-pathway to enhance its replication. In vitro and in vivo experiments confirmed that ISKNV infection activated the HIF-pathway, which in turn promoted ISKNV replication. These findings suggest that ISKNV actively manipulates the HIF-pathway. Co-immunoprecipitation experiments revealed that the ISKNV-encoded protein VP077R interacts with the Von Hippel-Lindau (VHL) protein at the HIF-binding region, competitively inhibiting the interaction of HIF-1α with VHL. This prevents HIF degradation and activates the HIF-pathway. Furthermore, VP077R interacts with factor-inhibiting HIF (FIH), recruiting FIH and S-phase kinase-associated protein 1 (Skp1) to form an FIH - VP077R - Skp1 complex. This complex promotes FIH protein degradation via ubiquitination, further activating the HIF-pathway. These findings indicated that ISKNV takes over the HIF-pathway by releasing two "brakes" on this pathway (VHL and FIH) via VP077R, facilitating virus replication. We speculate that hypoxia initiates a positive feedback loop between ISKNV VP077R and the HIF pathway, leading to the outbreak of ISKNV disease. This work offers valuable insights into the complex interactions between the environment, host, and virus.

Nitrite nitrogen stress disrupts the intestine bacterial community by altering host-community interactions in shrimp.

Environmental stress can disrupt the intricate interactions between the host and intestine microbiota, thereby impacting the host health. In this study, we aimed to elucidate the dynamic changes in the bacterial community within shrimp intestines under nitrite nitrogen (nitrite-N) stress and investigate potential host-related factors influencing these changes. Our results revealed a significant reduction in community diversity within the intestine exposed to nitrite-N compared to control conditions. Furthermore, distinct differences in community structures were observed between these two groups at 72 h and 120 h post-stress induction. Nitrite-N stress also altered the abundances of some bacterial species in the intestine dramatically. It is noteworthy that, in comparison to the 72 h, intestine bacterial community structure of stressed shrimp exhibited a significantly higher degree of dispersion after 120 h of nitrite-N stress when compared to control shrimp, and the relative abundance of numerous bacterial species experienced a substantial decrease or even reached 0 %. Moreover, it led to a reduction in bacterial community interactions and decreased competitiveness within the intestine microbiota. Notably, the influence of bacterial community assemblies in the shrimp intestine shifted from a stochastic process to a deterministic one after 24 h and 72 h of nitrite-N stress, returning to a stochastic process at 120 h. We further observed a close association between this phenomenon and host's response to nitrite-N stress. Expression levels of differentially expressed genes in the intestinal tissue significantly impact the intestine bacterial diversity and abundance of species. In particular, the significant decline in bacterial diversity and abundances of quite a few species in intestine was attributed to the up-regulation of peritrophin-48-like. Overall, nitrite-N stress indeed disrupted the intestine microbiota and changed the host-microbiota interactions of shrimp. This study offered novel insights into environment-host-microbiota interactions and also provided practical guidance for promoting healthy shrimp cultivation practices.

Effect of off-label targeted drugs on long-term survival in chronic thromboembolic pulmonary hypertension: Insights from a national multicentre prospective registry.

BACKGROUND AND OBJECTIVE: Off-label pulmonary arterial hypertension (PAH)-targeted drugs are commonly prescribed for non-operated chronic thromboembolic pulmonary hypertension (CTEPH), but their effect on the long-term prognosis of CTEPH remains unknown. This study investigated the effect of off-label PAH-targeted drugs on the long-term survival of CTEPH patients. METHODS: CTEPH patients were enrolled from a prospective multicentre national registry. Except for licensed riociguat and treprostinil, other PAH-targeted drugs were off-label. In the original and propensity score-matched (PSM) samples, five-year survival was compared in two groups: (a) patients not receiving off-label PAH-targeted drugs (control) versus (b) patients receiving off-label PAH-targeted drugs (treatment). The latter group was investigated for the effect of started off-label PAH-targeted drugs at baselines (initial) or during follow-up (subsequent). RESULTS: Of 347 enrolled patients, 212 were treated with off-label PAH-targeted drugs initially (n = 173) or subsequently (n = 39), and 135 were untreated. The 1-, 2-, 3- and 5-year survival of the treatment group was significantly higher than that of the control group (97.1% vs. 89.4%, 92.3% vs. 82.1%, 83.2% vs. 75.1% and 71.1% vs. 55.3%, respectively, log-rank test, p = 0.005). Initial treatment was correlated with better 5-year survival after excluding patients with subsequent treatment to reduce the immortal-time bias (hazard ratio: 0.611; 95% CI: 0.397-0.940; p = 0.025). In PSM samples, patients given initial treatment showed significantly better 5-year survival than untreated patients (68.9% vs. 49.3%, log-rank test, p = 0.008). CONCLUSION: Off-label targeted drugs contributed to improved long-term survival in CTEPH patients receiving pharmacotherapies.

Hypermethylated genome of a fish vertebrate iridovirus ISKNV plays important roles in viral infection.

Iridoviruses are nucleocytoplasmic large dsDNA viruses that infect invertebrates and ectothermic vertebrates. The hypermethylated genome of vertebrate iridoviruses is unique among animal viruses. However, the map and function of iridovirus genomic methylation remain unknown. Herein, the methylated genome of Infectious spleen and kidney necrosis virus (ISKNV, a fish iridovirus), and its role in viral infection, are investigated. The methylation level of ISKNV is 23.44%. The hypermethylated genome is essential for ISKNV amplification, but there is no correlation between hypermethylation and viral gene expression. The hypomethylated ISKNV (obtained via 5-Azacytidine) activates a strong immunoreaction in vitro and reduces its pathogenicity in vivo. The unmethylated viral DNA can induce a stronger immunoreaction in vitro, whereas inactivated hypomethylated ISKNV can induce a stronger immunoreaction in vivo, suggesting ISKNV may evade from immune system by increasing its genome methylation level. Our work provides new insights into the role of genome methylation in viral infection.

Oral delivery of bacteria expressing wsv108 gene-specific dsRNA protects shrimp from white spot syndrome virus (WSSV) infection.

Double-stranded RNA (dsRNA) can specifically inhibit gene expression by RNA interference and has important application potential in animal disease control. White spot syndrome virus (WSSV) is one of the most harmful pathogens in shrimp aquaculture, causing huge economic losses every year. In this study, we investigated the function of the WSSV-encoded wsv108 protein. We demonstrated that wsv108 could promote apoptosis by interacting with heat shock protein 70 (HSP70) and enhancing the expression of multiple apoptosis-related genes. Silencing of wsv108 gene by injection with specific dsRNA prepared by in vitro transcription significantly increased the survival rate of WSSV-infected shrimp and reduced the viral load in tissues, suggesting that wsv108 is important for WSSV pathogenicity. Based on this, we expressed the wsv108 specific dsRNA in engineered Escherichia coli. Oral feeding of this bacterium could inhibit the expression of wsv108, increase the survival rate of WSSV-infected shrimp, and decrease the viral load of WSSV in tissues. Therefore, this study developed a new method for treatment of WSSV disease by oral administration of bacterially expressed dsRNA against a novel therapeutic target molecule, which could be a potential candidate strategy for WSSV control in aquaculture.

Intestine bacterial community affects the growth of the Pacific white shrimp (Litopenaeus vannamei).

Increasing evidence suggests that intestine microorganisms are closely related to shrimp growth, but there is no existing experiment to prove this hypothesis. Here, we compared the intestine bacterial community of fast- and slow-growing shrimp at the same developmental stage with a marked difference in body size. Our results showed that the intestine bacterial communities of slow-growing shrimp exhibited less diversity but were more heterogeneous than those of fast-growing shrimp. Uncultured_bacterium_g_Candidatus Bacilloplasma, Tamlana agarivorans, Donghicola tyrosinivorans, and uncultured_bacterium_f_Flavobacteriaceae were overrepresented in the intestines of fast-growing shrimp, while Shimia marina, Vibrio sp., and Vibrio campbellii showed the opposite trends. We further found that the bacterial community composition was significantly correlated with shrimp length, and some bacterial species abundances were found to be significantly correlated with shrimp weight and length, including T. agarivorans and V. campbellii, which were chosen as indicators for a reverse gavage experiment. Finally, T. agarivorans was found to significantly promote shrimp growth after the experiment. Collectively, these results suggest that intestine bacterial community could be important factors in determining the growth of shrimp, indicating that specific bacteria could be tested in further studies against shrimp growth retardation. KEY POINTS: • A close relationship between intestine bacterial community and shrimp growth was proven by controllable experiments. • The bacterial signatures of the intestine were markedly different between slow- and fast-growing shrimp, and the relative abundances of some intestine bacterial species were correlated significantly with shrimp body size. • Reverse gavage by Tamlana agarivorans significantly promoted shrimp growth.

Biventricular intraventricular mechanical and electrical dyssynchrony in pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) leads to myocardial remodeling, manifesting as mechanical dyssynchrony (M-dys) and electrical dyssynchrony (E-dys), in both right (RV) and left ventricles (LV). However, the impacts of layer-specific intraventricular M-dys on biventricular functions and its association with E-dys in PAH remain unclear. Methods: Seventy-nine newly diagnosed patients with PAH undergoing cardiac magnetic resonance scanning were consecutively recruited between January 2011 and December 2017. The biventricular volumetric and layer-specific intraventricular M-dys were analyzed. The QRS duration z-scores were calculated after adjusting for age and sex. Results: 77.22 % of patients were female (mean age 30.30 ± 9.79 years; median follow-up 5.53 years). Further, 29 (36.71 %) patients succumbed to all-cause mortality by the end of the study. At the baseline, LV layer-specific intraventricular M-dys had apparent transmural gradients compared with RV in the radial and circumferential directions. However, deceased patients lost the transmural gradients. The LV longitudinal strain rate time to late diastolic peak in the myocardial region (LVmyoLSRTTLDPintra) predicted long-term survival. The Kaplan-Meier curve revealed that patients with PAH with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. Larger right ventricle (RV) intraventricular M-dys resulted in worse RV ejection fraction. However, larger LV intraventricular M-dys in the late diastolic phase indicated remarkable exercise capacity and higher LV stroke volume index. E-dys and intraventricular M-dys had no direct correlations. Conclusions: The layer-specific intraventricular M-dys had varying impacts on biventricular functions in PAH. PAH patients with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. LV intraventricular M-dys in the late diastolic phase needs more attention to precisely evaluate LV function.

Large B-cell Lymphoma with IRF4 Rearrangement in the Nasolacrimal Duct: A Clinicopathological Study of One Case and Literature Review.

BACKGROUND: Large B-cell lymphoma (LBCL) with interferon regulatory factor 4 (IRF4) rearrangement (LBCL-IRF4) is a rare subtype of LBCL, with a high prevalence in Waldeyer's ring as well as the neck, head and gastrointestinal lymph nodes. MATERIALS AND METHODS: A patient with 2-month clinical symptoms of nasal obstruction and facial swelling was reported in this short review. A nasal endoscopy examination revealed a neoplasm in the inferior nasal meatus. Both CT and enhanced MRI showed that a soft tissue occupied the nasolacrimal duct, with bone destruction, and extended into the left nasal cavity and left lacrimal gland area. Then, a biopsy of the neoplasm in the inferior nasal meatus was performed. RESULTS: HE staining results showed that neoplastic cells presented diffuse growth patterns, abundant cytoplasm, vacuole shape, lightly stained nuclei, and irregular nuclear membrane. Immunohistochemistry staining results revealed MUM1(+), Bcl6(+), CD20(+), CD79α(+), and CD10(+). FISH analyses detected positive IRF4 rearrangement. LBCL-IRF4 was diagnosed in the patient. The patient received treatment with four cycles of R-CHOP and two times of rituximab, followed up for 2 years, and finally got complete remission. CONCLUSION: For the first time, we summarize the imaging and pathological features, drug treatment, and curative effect of LBCL-IRF4 in the nasolacrimal duct.

Orange-spotted grouper nervous necrosis virus-encoded protein A induces interferon expression via RIG-I/MDA5-MAVS-TBK1-IRF3 signaling in fish cells.

IMPORTANCE: As a major pathogen, nervous necrosis virus (NNV) infects more than 120 fish species worldwide and is virulent to larvae and juvenile fish, hampering the development of the fish fry industry. Understanding virus-host interaction and underlying mechanisms is an important but largely unknown issue in fish virus studies. Here, using channel catfish ovary and fathead minnow cells as models for the study of innate immunity signaling, we found that NNV-encoded ProA activated interferon signaling via the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) pathway which was still suppressed by the infection of wild-type NNV. This finding has important implications for the comprehension of NNV protein function and the immune response from different cells. First, RIG-I is the key node for anti-NNV innate immunity. Second, the response intensity of RLR signaling determines the degree of NNV proliferation. This study expands our knowledge regarding the overview of signal pathways affected by NNV-encoded protein and also highlights potential directions for the control of aquatic viruses.

Imaging characteristics and prognostic factors of Behcet's disease with arterial involvement: A long-term follow-up study.

PURPOSE: To investigate the imaging characteristics and prognostic factors for the long-term survival of Behcet's disease (BD) with arterial involvement. METHODS: In this retrospective study, BD patients with arterial involvement were identified from January 2003 to January 2020. Arterial lesions were detected by ultrasonography, traditional arteriography, and/or computed tomography angiography (CTA). Cox proportional hazards regression analyses were performed to identify the prognostic factors. RESULTS: Totally, 84 BD patients with arterial involvement were identified (73.8 % males). The mean age at BD diagnosis was 39.1 ± 13.1 years. Arterial involvement was the initial manifestation in 33.3 % of the patients, and the median time from BD diagnosis to arterial involvement was 6 (IQR 1-15.5) years for the rest of patients. Systemic artery involvement and pulmonary artery involvement (PAI) were found in 64 and 27 patients, respectively. Approximately 94.0 % (79/84) of the patients had more than one artery involved concurrently or successively during the course of BD. Aneurysm/dilation was the most prevalent lesion in the aorta (76.0 %), while stenosis/occlusion was the main lesion of the coronary artery (90.9 %) and other aortic branches (74.5 %). Pulmonary hypertension was found in 70.4 % (19/27) of patients with PAI. The 5- and 10-year survival rates of BD patients with arterial involvement were 87.4 % and 84.1 %, respectively. Cardiac involvement (HR: 4.34) and pulmonary artery aneurysm/dilation (HR: 4.89) were independently associated with mortality. CONCLUSIONS: Arterial lesions associated with BD usually involve multiple arteries and manifest differently in different types of arteries. Cardiac involvement and pulmonary artery aneurysm/dilation are independent prognostic factors of BD patients with arterial involvement.

Orange-spotted grouper IFNh response to NNV or MSRV and its potential antiviral activities.

Type I interferon (IFN) plays a crucial role in the antiviral immune response. Nervous necrosis virus (NNV) and Micropterus salmoides rhabdovirus (MSRV) are the most important viruses in cultured larvae and juveniles, causing great economic losses to fish farming. To better understand the antiviral activities and immunoregulatory role of IFN from orange-spotted grouper (Epinephelus coioides), EcIFNh was cloned from NNV infected sample. EcIFNh has an open reading frame (ORF) of 552 bp and encodes a polypeptide of 183 amino acids. Phylogenetic tree analysis showed that EcIFNh was clustered into the IFNh branch. The tissue distribution analysis revealed that EcIFNh was highly expressed in the liver and brain of healthy orange-spotted grouper. The mRNA levels of EcIFNh were significantly upregulated after poly (I:C) stimulation and NNV or MSRV infection. Furthermore, the promoter of EcIFNh was characterized and significantly activated by EcMDA5, EcMAVS, EcSTING, EcIRF3, and EcIRF7 in the luciferase activity assays. We found that EcIFNh overexpression resisted the replication of NNV and MSRV, while EcIFNh silencing facilitated NNV replication in GB cells. In addition, EcIFNh recombinant protein (rEcIFNh) enhanced the immune response by inducing the expression of ISGs in vivo and in vitro, suggesting the potential application of rEcIFNh for anti-NNV and anti-MSRV. Taken together, our research may offer the foundation for virus-IFN system interaction in orange-spotted grouper.