Interfacial Spinel Local Interlocking Strategy Toward Structural Integrity in P3 Oxide Cathodes.

P3-layered transition oxide cathodes have garnered considerable attention owing to their high initial capacity, rapid Na+ kinetics, and less energy consumption during the synthesis process. Despite these merits, their practical application is hindered by the substantial capacity degradation resulting from unfavorable structural transformations, Mn dissolution and migration. In this study, we systematically investigated the failure mechanisms of P3 cathodes, encompassing Mn dissolution, migration, and the irreversible P3-O3' phase transition, culminating in severe structural collapse. To address these challenges, we proposed an interfacial spinel local interlocking strategy utilizing P3/spinel intergrowth oxide as a proof-of-concept material. As a result, P3/spinel intergrowth oxide cathodes demonstrated enhanced cycling performance. The effectiveness of suppressing Mn migration and maintaining local structure of interfacial spinel local interlocking strategy was validated through depth-etching X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and in situ synchrotron-based X-ray diffraction. This interfacial spinel local interlocking engineering strategy presents a promising avenue for the development of advanced cathode materials for sodium-ion batteries.

A positive feedback inhibition of isocitrate dehydrogenase 3ß on paired-box gene 6 promotes Alzheimer-like pathology.

Impaired brain glucose metabolism is an early indicator of Alzheimer's disease (AD); however, the fundamental mechanism is unknown. In this study, we found a substantial decline in isocitrate dehydrogenase 3ß (IDH3ß) levels, a critical tricarboxylic acid cycle enzyme, in AD patients and AD-transgenic mice's brains. Further investigations demonstrated that the knockdown of IDH3ß induced oxidation-phosphorylation uncoupling, leading to reduced energy metabolism and lactate accumulation. The resulting increased lactate, a source of lactyl, was found to promote histone lactylation, thereby enhancing the expression of paired-box gene 6 (PAX6). As an inhibitory transcription factor of IDH3ß, the elevated PAX6 in turn inhibited the expression of IDH3ß, leading to tau hyperphosphorylation, synapse impairment, and learning and memory deficits resembling those seen in AD. In AD-transgenic mice, upregulating IDH3ß and downregulating PAX6 were found to improve cognitive functioning and reverse AD-like pathologies. Collectively, our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3ß-lactate-PAX6-IDH3ß. Breaking this loop by upregulating IDH3ß or downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

Homocysteine-potentiated Kelch-like ECH-associated protein 1 promotes senescence of neuroblastoma 2a cells via inhibiting ubiquitination of ß-catenin.

Elevated serum homocysteine (Hcy) level is a risk factor for Alzheimer's disease (AD) and accelerates cell aging. However, the mechanism by which Hcy induces neuronal senescence remains largely unknown. In this study, we observed that Hcy significantly promoted senescence in neuroblastoma 2a (N2a) cells with elevated ß-catenin and Kelch-like ECH-associated protein 1 (KEAP1) levels. Intriguingly, Hcy promoted the interaction between KEAP1 and the Wilms tumor gene on the X chromosome (WTX) while hampering the ß-catenin-WTX interaction. Mechanistically, Hcy attenuated the methylation level of the KEAP1 promoter CpG island and activated KEAP1 transcription. However, a slow degradation rate rather than transcriptional activation contributed to the high level of ß-catenin. Hcy-upregulated KEAP1 competed with ß-catenin to bind to WTX. Knockdown of both ß-catenin and KEAP1 attenuated Hcy-induced senescence in N2a cells. Our data highlight a crucial role of the KEAP1-ß-catenin pathway in Hcy-induced neuronal-like senescence and uncover a promising target for AD treatment.

Linearly Interlinked Fe-Nx-Fe Single Atoms Catalyze High-Rate Sodium-Sulfur Batteries.

Linearly interlinked single atoms offer unprecedented physiochemical properties, but their synthesis for practical applications still poses significant challenges. Herein, linearly interlinked iron single-atom catalysts that are loaded onto interconnected carbon channels as cathodic sulfur hosts for room-temperature sodium-sulfur batteries are presented. The interlinked iron single-atom exhibits unique metallic iron bonds that facilitate the transfer of electrons to the sulfur cathode, thereby accelerating the reaction kinetics. Additionally, the columnated and interlinked carbon channels ensure rapid Na+ diffusion kinetics to support high-rate battery reactions. By combining the iron atomic chains and the topological carbon channels, the resulting sulfur cathodes demonstrate effective high-rate conversion performance while maintaining excellent stability. Remarkably, even after 5000 cycles at a current density of 10 A g-1, the Na-S battery retains a capacity of 325 mAh g-1. This work can open a new avenue in the design of catalysts and carbon ionic channels, paving the way to achieve sustainable and high-performance energy devices.

Distinct antiviral activities of IFNφ1 and IFNφ4 in zebrafish.

Interferons (IFNs) are a group of secreted cytokines that play a crucial role in antiviral immunity. Type I IFNs display functional disparities. In teleosts, type I IFNs are categorized into two subgroups containing one or two pairs of disulfide bonds. However, their functional differences have not been fully elucidated. In this study, we comparatively characterized the antiviral activities of zebrafish IFNφ1 and IFNφ4 belonging to the group I type I IFNs. It was found that ifnφ1 and ifnφ4 were differentially modulated during viral infection. Although both IFNφ1 and IFNφ4 activated JAK-STAT signaling pathway via CRFB1/CRFB5 receptor complex, IFNφ4 was less potent in inducing phosphorylation of STAT1a, STAT1b and STAT2 and the expression of antiviral genes than IFNφ1, thereby conferring weaker antiviral resistance of target cells. Taken together, our results provide insights into the functional divergence of type I IFNs in lower vertebrates.

[Impacts of Extreme Climate Events at Different Altitudinal Gradients on Vegetation NPP in Songhua River Basin].

Vegetation net primary production (NPP) is an essential index for determining the quality of terrestrial ecosystems and their potential carbon storage ability. The impacts of extreme climate events on vegetation NPP are different under different altitude gradients. However, the research on the impact of extreme climate events on the spatial variation in vegetation NPP and the coupling effects under different altitude conditions remain insufficient. Using the MOD17A3HGF remote sensing data set and RClimDex 1.9 software, the vegetation NPP and 10 extreme climate indices in the Songhua River Basin from 2001 to 2020 were calculated, respectively. The spatial and temporal evolution characteristics of vegetation NPP and its response mechanism to extreme climate events in the Songhua River Basin under different altitude gradients were analyzed by means of trend analysis, correlation analysis, regression analysis, GeoDetector, and relative importance analysis. The results showed that:① the vegetation NPP (calculated by C) in the Songhua River Basin increased significantly at the rate of 4.13 g·(m2·a)-1 from 2001 to 2020 (P < 0.01), and the rates of 3.65, 4.04, 4.70, 5.09, and 4.57 g·(m2·a)-1 at the altitude gradients of 29-255, 255-440, 440-658, 658-935, and 935-2 589 m, respectively (P < 0.01). ② The spatial distribution pattern of vegetation NPP presented "high around and low in the middle," and the fluctuation of vegetation NPP in high altitude areas was more obvious than that in low altitude areas; for example, the average value of vegetation NPP at an altitude gradient from 29 to 255 m had a lower value, whereas the other altitude gradients had higher mean values than the mean value of the basin. ③ The extreme precipitation events in the Songhua River Basin were the main influencing factors of vegetation NPP, i.e., the vegetation NPP in low-altitude areas was mainly affected by extreme precipitation events, whereas the values in high-altitude areas were affected by both extreme precipitation events and extreme temperature events. The results of this research can provide a scientific basis for improving the carbon cycle model of the terrestrial ecosystem in the Songhua River Basin, quantifying the ability of carbon storage of vegetation and formulating policies to deal with climate change.

An Intrinsic Stable Layered Oxide Cathode for Practical Sodium-Ion Battery: Solid Solution Reaction, Near-Zero-Strain and Marvelous Water Stability.

Non-aqueous solvents, in particular N,N-dimethylaniline (NMP), are widely applied for electrode fabrication since most sodium layered oxide cathode materials are readily damaged by water molecules. However, the expensive price and poisonousness of NMP unquestionably increase the cost of preparation and post-processing. Therefore, developing an intrinsically stable cathode material that can implement the water-soluble binder to fabricate an electrode is urgent. Herein, a stable nanosheet-like Mn-based cathode material is synthesized as a prototype to verify its practical applicability in sodium-ion batteries (SIBs). The as-prepared material displays excellent electrochemical performance and remarkable water stability, and it still maintains a satisfactory performance of 79.6% capacity retention after 500 cycles even after water treatment. The in situ X-ray diffraction (XRD) demonstrates that the synthesized material shows an absolute solid-solution reaction mechanism and near-zero-strain. Moreover, the electrochemical performance of the electrode fabricated with a water-soluble binder shows excellent long-cycling stability (67.9% capacity retention after 500 cycles). This work may offer new insights into the rational design of marvelous water stability cathode materials for practical SIBs.

Epidemiology of Influenza-like Illness and Respiratory Viral Etiology in Adult Patients in Taiyuan City, Shanxi Province, China between 2018 and 2019.

To determine the epidemiological status of influenza and understand the distribution of common respiratory viruses in adult patients with influenza-like illness (ILI) cases in Taiyuan City, Shanxi Province, China, epidemiological data between 2018 and 2019 were retrieved from the China Influenza Surveillance Information System, and two sentinel ILI surveillance hospitals were selected for sample collection. All specimens were screened for influenza virus (IFV) and the other 14 common respiratory viruses using real-time polymerase chain reaction. The results of the 2-year ILI surveillance showed that 26,205 (1.37%) of the 1,907,869 outpatients and emergency patients presented with ILI, with an average annual incidence of 297.75 per 100,000 individuals, and ILI cases were predominant in children <15 years (21,348 patients, 81.47%). Of the 2713 specimens collected from adult patients with ILI, the overall detection rate of respiratory viruses was 20.13%, with IFV being the most frequently detected (11.79%) and at a relatively lower rate than other respiratory viruses. Further subtype analysis indicated an alternating or mixed prevalence of H1N1 (2009), H3N2, Victoria, and Yamagata subtypes. This study provides a baseline epidemiological characterization of ILI and highlights the need for a nationwide detection and surveillance system for multiple respiratory pathogens.

The Biological Functions and Intestinal Inflammation Regulation of IL-21 in Grass Carp (Ctenopharyngodon idella) during Infection with Aeromonas hydrophila.

Interleukin (IL) 21 is a pleiotropic cytokine that plays an important role in regulating innate and adaptive immune responses. In fish, the biological functions and cell source of IL-21 remain largely unknown. In this study, we performed qRT-PCR, Western blotting and immunofluorescent microscopy to examine the expression of IL-21 at the mRNA and protein levels. We found that il21 expression was induced in the primary head kidney leukocytes of grass carp (Ctenopharyngodon idella) by heat-inactivated Aeromonas hydrophila (A. hydrophila) and LPS and in tissues after infection with A. hydrophila. Recombinant IL-21 protein produced in the CHO-S cells was effective in elevating the expression of antibacterial genes, including ß-defensin and lysozyme, and, interestingly, inhibited the NF-κB signaling pathway. Furthermore, we investigated the response of the IL-21 expressing cells to A. hydrophila infection. Immunofluorescent assay showed that IL-21 protein was detected in the CD3γ/δ T cells and was markedly accumulated in the anterior, middle and posterior intestine. Collectively, the results indicate that IL-21 plays an important role in regulating the intestinal inflammation induced by bacterial infection in grass carp.

Sodium Layered/Tunnel Intergrowth Oxide Cathodes: Formation Process, Interlocking Chemistry, and Electrochemical Performance.

Manganese-based layered oxides are prospective cathode materials for sodium-ion batteries (SIBs) due to their low cost and high theoretical capacities. The biphasic intergrowth structure of layered cathode materials is essential for improving the sodium storage performance, which is attributed to the synergistic effect between the two phases. However, the in-depth formation mechanism of biphasic intergrowth materials remains unclear. Herein, the layered/tunnel intergrowth Na0.6MnO2 (LT-NaMO) as a model material was successfully prepared, and their formation processes and electrochemical performance were systematically investigated. In situ high-temperature X-ray diffraction displays the detailed evolution process and excellent thermal stability of the layered/tunnel intergrowth structure. Furthermore, severe structural strain and large lattice volume changes are significantly mitigated by the interlocking effect between the phase interfaces, which further enhances the structural stability of the cathode materials during the charging/discharging process. Consequently, the LT-NaMO cathode displays fast Na+ transport kinetics with a remarkable capacity retention of ∼70.5% over 300 cycles at 5C, and its assembled full cell with hard carbon also exhibits high energy density. These findings highlight the superior electrochemical performance of intergrowth materials due to interlocking effects between layered and tunnel structures and also provide unique insights into the construction of intergrowth cathode materials for SIBs.

DDX5 inhibits type I IFN production by promoting degradation of TBK1 and disrupting formation of TBK1 - TRAF3 complex.

DExD/H-box helicase (DDX) 5 belongs to the DExD/H-box helicase family. DDX family members play differential roles in the regulation of innate antiviral immune response. However, whether DDX5 is involved in antiviral immunity remains unclear. In this study, we found that DDX5 serves as a negative regulator of type I interferon (IFN) response. Overexpression of DDX5 inhibited IFN production induced by Spring viremia of carp virus (SVCV) and poly(I:C) and enhanced virus replication by targeting key elements of the RLR signaling pathway (MAVS, MITA, TBK1, IRF3 and IRF7). Mechanistically, DDX5 directly interacted with TBK1 to promote its autophagy-mediated degradation. Moreover, DDX5 was shown to block the interaction between TRAF3 and TBK1, hence preventing nuclear translocation of IRF3. Together, these data shed light on the roles of DDX5 in regulating IFN response.

Developing a nomogram-based scoring model to estimate the risk of pulmonary embolism in respiratory department patients suspected of pulmonary embolisms.

Objective: Pulmonary embolisms (PE) are clinically challenging because of their high morbidity and mortality. This study aimed to create a nomogram to accurately predict the risk of PE in respiratory department patients in order to enhance their medical treatment and management. Methods: This study utilized a retrospective method to collect information on medical history, complications, specific clinical characteristics, and laboratory biomarker results of suspected PE patients who were admitted to the respiratory department at Affiliated Dongyang Hospital of Wenzhou Medical University between January 2012 and December 2021. This study involved a total of 3,511 patients who were randomly divided into a training group (six parts) and a validation group (four parts) based on a 6:4 ratio. The LASSO regression and multivariate logistic regression were used to develop a scoring model using a nomogram. The performance of the model was evaluated using receiver operating characteristic curve (AUC), calibration curve, and clinical decision curve. Results: Our research included more than 50 features from 3,511 patients. The nomogram-based scoring model was established using six predictive features including age, smoke, temperature, systolic pressure, D-dimer, and fibrinogen, which achieved AUC values of 0.746 in the training cohort (95% CI 0.720-0.765) and 0.724 in the validation cohort (95% CI 0.695-0.753). The results of the calibration curve revealed a strong consistency between probability predicted by the nomogram and actual probability. The decision curve analysis (DCA) also demonstrated that the nomogram-based scoring model produced a favorable net clinical benefit. Conclusion: In this study, we successfully developed a novel numerical model that can predict the risk of PE in respiratory department patients suspected of PE, which can not only appropriately select PE prevention strategies but also decrease unnecessary computed tomographic pulmonary angiography (CTPA) scans and their adverse effects.

The first crystal structure of CD8αα from a cartilaginous fish.

Introduction: Cartilaginous fishes are the most evolutionary-distant vertebrates from mammals and possess an immunoglobulin (Ig)- and T cell-mediated adaptive immunity. CD8 is the hallmark receptor of cytotoxic T cells and is required for the formation of T cell receptor-major histocompatibility complex (TCR-MHC) class I complexes. Methods: RACE PCR was used to obtain gene sequences. Direct dilution was applied for the refolding of denatured recombinant CD8 protein. Hanging-drop vapor diffusion method was performed for protein crystallization. Results: In this study, CD8α and CD8ß orthologues (termed ScCD8α and ScCD8ß) were identified in small-spotted catshark (Scyliorhinus canicula). Both ScCD8α and ScCD8ß possess an extracellular immunoglobulin superfamily (IgSF) V domain as in previously identified CD8 proteins. The genes encoding CD8α and CD8ß are tandemly linked in the genomes of all jawed vertebrates studied, suggesting that they were duplicated from a common ancestral gene before the divergence of cartilaginous fishes and other vertebrates. We determined the crystal structure of the ScCD8α ectodomain homodimer at a resolution of 1.35 Å and show that it exhibits the typical topological structure of CD8α from endotherms. As in mammals, the homodimer formation of ScCD8αα relies upon interactions within a hydrophobic core although this differs in position and amino acid composition. Importantly, ScCD8αα shares the canonical cavity required for interaction with peptide-loaded MHC I in mammals. Furthermore, it was found that ScCD8α can co-immunoprecipitate with ScCD8ß, indicating that it can form both homodimeric and heterodimeric complexes. Conclusion: Our results expand the current knowledge of vertebrate CD8 dimerization and the interaction between CD8α with p/MHC I from an evolutionary perspective.

Phylogeny and expression of ADAM10 and ADAM17 homologs in lamprey.

The ADAMs (a disintegrin and metalloproteinase) play regulatory roles in cell adhesion, migration and proteolysis. To explore the origin and evolution of ADAMs, this study identified the homologs of adam10 and adam17 in Lampetra morii and Lampetra japonica. Sequence analysis revealed that they share the same genomic structures with their counterparts in jawed vertebrates. The putative proteins possess conserved motifs, including a furin cut site (RXXR) for precursor processing, an enzyme catalytic motif (HEXGEHXXGXXH) for hydrolysis, and a Ca2+-binding motif (CGNXXXEXGEXCD) for stabilizing protein structure. In addition, a substrate recognition domain is present at the membrane-proximal region of lamprey ADAM17. The cytoplasmic region of lamprey ADAM10 contains a potential threonine phosphorylation site which has been shown to be activated by protein kinase C (PKC) in mammals. Both the adam10 and adam17 genes were constitutively expressed in the brain, kidney, and gills and were differentially regulated in the primary blood leukocytes by lipopolysaccharide (LPS) and pokeweed mitogen (PWM). Adam10 was induced by LPS but not PWM; conversely, adam17 was induced by PWM but not LPS. Taken together, our results suggest that the activation pathways and functions of ADAM10 and ADAM17 are conserved in agnathans.

TL1A induces apoptosis via DR3 in grass carp (Ctenopharyngodon idella).

Tumor necrosis factor like ligand 1A (TL1A), a member of TNF superfamily, regulates inflammatory response and immune defense. TL1A homologues have recently been discovered in fish, but their functions have not been studied. In this study, a TL1A homologue was identified in grass carp (Ctenopharyngodon idella) and its bioactivities were investigated. The grass carp tl1a (Citl1a) gene was constitutively expressed in tissues, with the highest expression detected in the liver. It was upregulated in response to infection with Aeromonas hydrophila. The recombinant CiTL1A was produced in bacteria and was shown to stimulate the expression of il1ß, tnfα, caspase 8 and ifnγ in the primary head kidney leucocytes. In addition, co-immunoprecipitation assay revealed that CiTL1A interacted with DR3 and induced apoptosis via activation of DR3. The results demonstrate that TL1A regulates inflammation and apoptosis and is involved in the immune defense against bacterial infection in fish.

IL-4/13 expressing CD3γ/δ+ T cells regulate mucosal immunity in response to Flavobacterium columnare infection in grass carp.

Interleukin (IL) 4 and 13 are signature cytokines orchestrating Th2 immune response. Teleost fish have two homologs, termed IL-4/13A and IL-4/13B, and have been functionally characterized. However, what cells express IL-4/13A and IL-4/13B has not been investigated in fish. In this work, the recombinant IL-4/13A and IL-4/13B proteins of grass carp (Ctenopharyngodon idella) were produced in the Escherichia coli (E. coli) cells and purified. Monoclonal antibodies (mAbs) against the recombinant CiIL-4/13A and CiIL-4/13B proteins were prepared and characterized. Western blotting analysis showed that the CiIL-4/13A and CiIL-4/13B mAbs could specifically recognize the recombinant proteins expressed in the E. coli cells and HEK293T cells and did not cross-react with each other. Confocal microscopy revealed that the CiIL-4/13A+ and CiIL-4/13B+ cells were present in the gills, intestine and spleen and could be upregulated in fish infected with Flavobacterium columnare (F. columnare). Interestingly, the cells expressing CiIL-4/13A and CiIL-4/13B were mostly CD3γ/δ+ cells. The CD3γ/δ+/IL-4/13A+ and CD3γ/δ+/IL-4/13B+ cells were significantly upregulated in the gill filaments and the intestinal mucosa after F. columnare infection. Our results imply that the CD3γ/δ+/IL-4/13A+ and CD3γ/δ+/IL-4/13B+ cells are important for homeostasis and the regulation of mucosal immunity.

The Meteorin-like cytokine is upregulated in grass carp after infection with Aeromonas hydrophila.

Meteorin-like (Metrnl) is a novel immune regulatory factor or adipokine which is mainly produced by activated macrophages. In teleost fish, two homologs are present. In this study, monoclonal antibodies were prepared against recombinant grass carp (Ctenopharyngodon idella, Ci) Metrnl-a in mice and characterized by Western blotting, flow cytometry and immunofluorescent microscopy. In grass carp infected with Aeromonus hydrophila (A. hydrophila), the cells expressing CiMetrnl-a markedly increased in the gills, head kidney and intestine. In the inflamed intestine caused by A. hydrophila infection, the CiMetrnl-a producing cells were detected mainly in the mucosal layer of anterior, middle and posterior segments. Consistently, qRT-PCR analysis showed that the mRNA expression of CiMetrnl-a was markedly induced. Our results suggest that CiMetrnl-a is involved in regulating intestine inflammation caused by bacterial infection.

Effectiveness and Accuracy of a Patient-Specific Instrumentation System for Total Hip Arthroplasty.

OBJECTIVE: Traditional total hip arthroplasty (THA) is often performed by visual inspection due to the lack of reliable reference, which results in inappropriate position of prosthesis and poor outcomes. This study attempts to introduce a novel patient-specific instrumentation (PSI) system and assess its effectiveness and accuracy compared with freehand operation and robot system through bone model experiments. METHODS: Equally divide 30 sawbone models into the freehand group, PSI group, and robot group. Ten sets of prosthesis parameters were randomly generated as planning, and the three groups underwent simulated THA depending on these parameters. After the placement of the femoral prosthesis, the acetabular anteversion plan was adjusted in the PSI and robot groups so that the combined anteversion was maintained before and after adjustment. After the surgery, the actual prosthesis parameters of all bone models were measured and analyzed statistically. RESULTS: No statistically significant difference was found in femoral anteversion error among the three groups (p = 0.951). The errors of acetabular cup anteversion, acetabular cup abduction, and combined anteversion in PSI group were 3.92° (2.94°, 4.62°), 5.65° (4.63°, 6.70°), and 3.93° (2.94°, 4.62°), respectively, which were significantly smaller than those in the freehand group [11.84° (9.92°, 13.87°), 13.54° (9.81°, 15.21°), 16.04° (8.18°, 19.25°), respectively, p < 0.05], but significantly larger than those in the robot group [1.34° (0.98°, 1.70°), 1.80° (1°, 2.02°), 1.34° (0.98°, 1.70°), respectively, p < 0.05]. CONCLUSION: Compared with the traditional freehand operation, the patient-specific instrumentation system is feasible in total hip arthroplasty because it improves the accuracy of prosthesis placement. In addition, the rapid measurement of intraoperative femoral prosthesis parameters can help surgeons optimize preoperative planning.

IL-27 suppresses spring viremia of carp virus replication in zebrafish.

Interleukin (IL) 27 is a member of the IL-12 family and is a heterodimeric cytokine composed of IL-27A and Epstein-Barr virus-induced 3 (EBI3). It plays an important role in regulating inflammation and cancer progression. IL-27A not only functions by dimerizing with EBI3 but also acts alone. Here, we report that IL-27A and EBI3 suppress spring viremia of carp virus (SVCV) replication in zebrafish. Expression analysis reveals that il-27a and ebi3 were significantly upregulated in the ZF4 cells by SVCV and poly(I:C), and in the zebrafish caudal fin (ZFIN) cells overexpressed with SVCV genes. Interestingly, il-27a and ebi3 were not modulated by IFNφ1, indicating that they are not IFN stimulated genes (ISGs). Furthermore, overexpression of IL-27A and EBI3 alone inhibited SVCV replication in the EPC cells, but less potent than co-expression of IL-27A and EBI3. Intriguingly, IL-27A could not induce the expression of irf3, ifn, isg15 and mx1. Taken together, our results demonstrate that IL-27A and EBI3 activate innate antiviral response in an IFN independent manner in zebrafish.

Expression and functional characterization of three ß-defensins in grass carp (Ctenopharyngodon idella).

ß-defensins (BDs) are a group of cysteine-rich cationic antimicrobial peptides and play important roles in the first line of defense against infection. In this study, the expression and antibacterial activities of three grass carp (Ctenopharyngodon idella) (Ci) ß-defensin (BD) peptides were comparatively investigated. Expression analysis reveals that CiBD1-3 were constitutively expressed in tissues, with the highest expression detected in the skin. The CiBD-1 transcripts were more abundant than CiBD-2 and CiBD-3. In the primary head kidney leukocytes, CiBDs were induced by PHA, LPS, poly(I:C) and cytokines such as IL-1ß and IFN-γ. In vivo challenge of fish with Aeromonas hydrophila resulted in the up-regulation of CiBDs in the head kidney and hindgut. To determine the biological activities, recombinant CiBD proteins were produced in the HEK293-F cells and purified for the minimum inhibitory concentration assay. It was found that all three recombinant CiBD proteins were effective to inhibit the growth of Gram-negative fish bacterial pathogens including Aeromonas hydrophila, Edwardsiella tarda, Flavobacterium columnare and Klebsiella pneumoniae and Gram-positive Staphylococcus aureus. CiBD-2 and CiBD-3 were more effective than CiBD-1. Our results demonstrate that all the three CiBDs have broad antibacterial activity against fish bacterial pathogens.