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The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia.This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10-20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions-Severity (CGI-S) scores, respectively.A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were - 33.6 for the AOM group and - 34.8 in the oral aripiprazole group, respectively, with a difference of - 1.2 (95% CI: - 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was - 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was - 2.2 and - 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively.This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia.ClinicalTrials.gov identifier: NCT03172871.

Along with the increasing number of prefabricated buildings being constructed in China each year, the incident rate of hoisting operations has been continuously rising. In order to improve construction safety in hoisting operations of prefabricated buildings, this paper analyzes the construction workers’ unsafe behaviors using the Hazard and Operability (HAZOP) method. A questionnaire survey and a literature review were first performed to gather information on safety risks and influencing factors during each stage of hoisting operations, and the survey results were statistically analyzed using the SPSS software. Next, HAZOP was applied to identify the deviation and change of the unsafe behaviors as well as their causes, consequences, and countermeasures. Finally, a case study was presented to verify the effectiveness of the countermeasures through a comparison and evaluation method from experimental economics. This paper demonstrates the use of HAZOP to analyze construction workers’ unsafe behaviors in hoisting operations of prefabricated buildings, and effective countermeasures in each stage of hoisting operations are proposed to mitigate unsafe behaviors. This paper therefore provides an innovative method and a theoretical foundation for reducing unsafe behaviors in hoisting operations of prefabricated buildings and serves as a reference for decision-making for hoisting safety policies in prefabricated construction projects.

We present a simple and effective scheme of a dynamic switch for DNA nanostructures. Under such a framework of toehold-free strand displacement, blocking strands at an excess amount are applied to displace the complementation of specific segments of paired duplexes. The functional mechanism of the scheme is illustrated by modelling the base pairing kinetics of competing strands on a target strand. Simulation reveals the unique properties of toehold-free strand displacement in equilibrium control, which can be leveraged for information processing. Based on the controllable dynamics in the binding of preformed DNA nanostructures, a multi-input-multi-output (MIMO) Boolean function is controlled by the presence of the blockers. In conclusion, we implement two MIMO Boolean functions (one with 4-bit input and 2-bit output, and the other with 16-bit input and 8-bit output) to showcase the controllable dynamics., Synthetic DNA constructs can to used to recognise and respond to input signals. Here the authors present complex DNA nanostructures with toehold-free strand displacement for generation of ON/OFF switches and Boolean gates.

Aeromonas hydrophila infections are common in aquaculture. Our previous studies found that the A. hydrophila B11 strain can survive in fish macrophages for at least 24 h and the two-component system EnvZ/OmpR may be involved in intracellular survival. To reveal the role and mechanism of the two-component system EnvZ/OmpR in intracellular survival of A. hydrophila, the genes of envZ/ompR were silenced by shRNAi. The results showed that the survival rates of the envZ-RNAi and ompR-RNAi strains were only 2.05% and 3.75%, respectively, which were decreased by 91% and 83.6% compared with that of the wild-type strain. The escape ability of envZ-RNAi and ompR-RNAi was also decreased by 51.4% and 19.7%, respectively. The comparative transcriptome analysis revealed that the functional genes directly related to bacterial intracellular survival mainly included the genes related to anti-stress capacity, and the genes related to Zn

Bacteria adhesion to fish mucus is a crucial virulence mechanism. As the initial step of bacterial infection, adhesion is impacted by bacterial motility and environmental conditions. However, its molecular mechanism is yet unclear. In this study, a significant decrease in gene expression of adhesion-deficient Vibrio harveyi was observed when the bacteria were subjected by Cu

Bacterial pathogen-host interactions are highly dynamic, regulated processes that have been primarily investigated using in vitro assays. The dynamics of bacterial pathogen-host interplay in vivo are poorly understood. Using time-resolved dual RNA-seq in a Pseudomonas plecoglossicida-Epinephelus coioides infection model, we observed that bacterial genes encoding classical virulence factors and host genes involved in immune regulation were dynamically expressed during infection. Using network inferencing, we were able to predict interspecies regulatory networks linking bacterial virulence genes to host immune genes. Together with gene co-expression network analysis of the pathogen, secY was predicted to be a key virulence gene for P. plecoglossicida pathogenicity in the host, fliN was predicted to be a less important virulence gene. The results of bioinformatics prediction were confirmed by animal infection experiments. Our work provides the first paradigm to study dynamic alterations of bacterial pathogen and host interactions based on the elucidation of time-resolved interactive transcriptomes in vivo, and may be developed into a novel and universal method for revealing the true complexity of the bacterial infection process.

Pseudomonas plecoglossicida is a Gram-negative aerobic bacterium that causes high mortality and serious economic losses in some commercial marine fish. Expression of secY was found to be significantly upregulated at 18 °C compared to 28 °C by RNA-seq and qRT-PCR. All five tested recombinant vectors (pCM130/tac + shRNA) significantly reduced secY mRNA levels in P. plecoglossicida. The recombinant vector encoding shRNA-1165 exhibited the best gene-silencing efficiency, 82.4% and was used to create an RNAi strain for further studies. Compared with the wildtype strain, infections of Larimichthys crocea with the RNAi strain resulted in a 2-day delay in onset time and a 35% reduction in mortality, as well as the alleviation of spleen symptoms. The spleens of L. crocea infected by the wild type or RNAi strain of P. plecoglossicida were subjected to dual RNA-seq at 2 dpi. Compared with the wildtype strain, infection of P. plecoglossicida with the RNAi strain resulted in significant changes in the transcriptomes of both host and pathogen. KEGG analysis showed that the complement and coagulation cascade and the Toll-like receptor signalling pathway were the most enriched host pathways. In the pathogen, genes of the “Sec secretion system” were significantly downregulated. This downregulation of “Sec secretion system” genes hindered the secretion of bacterial proteins and reduced the virulence of P. plecoglossicida. Thus, it was easier for L. crocea to clear the RNAi strain of P. plecoglossicida, and the immune response was similarly reduced. The results indicated that secY was a virulence gene of P. plecoglossicida and played roles in the host-pathogen interactions of L. crocea and P. plecoglossicida.

As an important pathogen in aquaculture, Pseudomonas plecoglossicida has caused heavy losses. The expression of an ABC transporter gene-L321_23611 of P. plecoglossicida at 18 °C was found significant higher than those at 28 °C by RNA-seq and qRT-PCR. RNAi significantly reduced the content of L321_23611 mRNA in P. plecoglossicida with a maximal decrease of 89.2%. Compared with the wild type strain, the infection of L321_23611-RNAi strain resulted in the reduction in mortality and the onset time delay of a kind of marine teleosts, Epinephelus coioides. The results of dual RNA-seq showed that the RNAi of L321_23611 resulted in a significant change in both pathogen and host transcriptome in the spleens of infected E. coioides. The result of GO and KEGG analysis from dual RNA-seq data showed both host genes of chemokine signaling pathway, coagulation and complement system, hematopoietic cell lineage pathway as well as hemoglobin complex GO term and pathogenic genes of bacterial-type flagellum-dependent cell mortality GO term and flagellar assembly, biosynthesis of amino acids and lysine biosynthesis systems pathways were mainly affected by L321_23611 gene of P. plecoglossicida. The results indicated that: 1. ABC transporter gene-L321_23611 was a virulent gene of P. plecoglossicida. 2. Both the activation of the host immune pathways and depression of pathogenic virulence-related pathways facilitated E. coioides to remove L321_23611-RNAi strain than the wild type strain of P. plecoglossicida.

Several bacteria have been defined as extracellular pathogens; however, in recent years, it has been confirmed that they have the ability to survive and escape the attack of host phagocytes, thus causing further infection. Previous studies have shown that Aeromonas hydrophila could survive in fish macrophages; however, the mechanism remains unknown. In this study, sodA and sodB of the strain A. hydrophila B11 were stable silenced by shRNA. The survival rates of intracellular sodA-RNAi and sodB-RNAi decreased by 91.8% and 74.9% and the immune escape rates decreased by about 32% and 92% respectively. At the same time, reactive oxygen species (ROS) in fish macrophages that phagocytosed sodA-RNAi and sodB-RNAi increased by 40% and 32.6%, respectively, compared to those of macrophages that phagocytosed the wild-type strain. Compared to sodA, the expression of sodB predominates in A. hydrophila without oxidative stress; however, when exposed to oxidative stress, the magnitude of up-regulation of sodA expression is significantly higher than that of sodB. With increased of methyl viologen concentration, the survival rates of sodA-RNAi and sodB-RNAi were significantly decreased. The expressions of sodA and sodB did not affect the growth of A. hydrophila without oxidative stress, but the inhibition of sodA and sodB expression led to a slight decrease in bacterial growth under oxidative stress. These results indicated that (1) sodA and sodB play an important role in the process of bacterial resistance to ROS damage in host phagocytic cells, allowing them to survive or even escape fish macrophages; (2) the sodB expression was dominant in A. hydrophila without oxidative stress, the sodA expression was up-regulated more significantly under oxidative stress, and sodA and sodB contributed equally to the process of bacterial resistance to ROS; (3) sodA and sodB complement each other and cooperate in the process of intracellular survival of bacteria to protect against ROS damage.

Survival in host macrophages is an effective strategy for pathogenic bacteria to spread. Aeromonas hydrophila has been found to survive in fish macrophages, but the mechanisms remain unknown. In this paper, the roles and possible mechanisms of IcmF in bacterial survival in fish macrophages were investigated. First, a stable silencing strain icmF-RNAi was constructed by shRNA and RT-qPCR confirmed the expression of icmF was down-regulated by 94.42%. The expression of Hcp, DotU and VgrG was also decreased in icmF-RNAi. The intracellular survival rate of the wild-type strain was 92.3%, while the survival rate of icmF-RNAi was only 20.58%. The escape rate of the wild-type strain was 20%, while that of the icmF-RNAi was only 7.5%. Further studies indicated that the expression of icmF can significantly affect the adhesion, biofilm formation, motility and acid resistance of A. hydrophila, but has no significant effect on the growth of A. hydrophila even under the stress of H2 O2 . The results indicated that IcmF of A. hydrophila not only acts as a structural protein which participates in virulence-related characteristics such as bacterial motility, adhesion and biofilm formation, but also acts as a key functional protein which participates in the interaction between bacteria and host macrophages.

The incidence of Vibrio alginolyticus infections has increased in recent years due to the influence of climate change and rising sea temperature. Vibrio virulence regulatory RNA 1 (Vvrr1) is a newly found noncoding RNA (ncRNA) predicted to be closely related to the adhesion ability of V. alginolyticus based on the previous RNA-seq. In this study, the target genes of Vvrr1 were fully screened and verified by constructing Vvrr1-overexpressing strains and using the proteome sequencing technology. Pyruvate kinase I (pykF) gene was predicted to be a chief target gene of Vvrr1 involved in virulence regulation. The adhesion ability, biofilm formation and virulence were significantly reduced in the Vvrr1-overexpressing and the pykF-silenced strain compared with the wild strains. Similar to the overexpression of Vvrr1, the silencing of pykF also reduced the expression level of virulence genes, such as ndk, eno, sdhB, glpF, and cysH. Meanwhile, by constructing the "pykF-GFP" fusion expression plasmid and using the GFP reporter gene analysis in Escherichia coli, the fluorescence intensity of the strain containing Vvrr1 whole ncRNA sequence vector was found to be significantly weakened. These indicated that Vvrr1 participated in the virulence regulation mechanism of V. alginolyticus by interacting with the virulence gene pykF.

Active exercise for upper limb training has been widely used to improve hemiplegic upper limb function, and its effect may be boosted by extrinsic visual feedback. The passive movement of the hemiplegic upper limb is also commonly used. We conducted a functional near-infrared spectroscopy experiment to compare cortical activation during the following three conditions: active left upper limb movement (on the hemiplegic sides in stroke patients), with or without extrinsic motor performance visual feedback (LAV, LAnV), and passive left upper limb movement (hemiplegic sides in stroke patients) (LP) in stroke patients and healthy controls. Twenty patients with right hemispheric stroke and 20 healthy controls were recruited for this study. Hemodynamic changes were detected during left upper limb movements (on the hemiplegic sides in stroke patients) under the above three conditions in the sensorimotor cortex (SMC), supplementary motor area (SMA), and premotor cortex (PMC). There was no significant difference in the level of cortical activation between patients with stroke and healthy subjects during the three conditions. Both the LAV and LAnV induced significantly higher activation in the contralateral SMA and PMC than in the LP. Extrinsic visual feedback led to additional activation in the contralateral PMC and SMA, but this was not statistically significant. Our study indicates that active upper-limb movement appears to induce higher cortical activation than that elicited by passive movement in both stroke patients and the healthy population. Extrinsic motor performance in the form of visual feedback provided during active movement may facilitate sensorimotor areas over the contralateral hemisphere.

The rapid growth of national economy has led to more and more large-scale construction projects in China. The traditional project management mode is difficult to adapt to the requirements of the large construction projects. Inefficient exchange of information, massive waste of resources, and declining rate of profit have hindered the development of the large-scale construction projects. The SWOT method is used to analyze the supply chain of large-scale construction projects and 16 factors are obtained. The weight of judgment matrix is calculated by expert system scoring combined with analytic hierarchy process. According to the results, this article draws the strategic quadrilateral and obtains the order of supply chain strategy selection for large-scale construction projects. This article provides a new idea for selecting supply chain management strategy scientifically.

Background Trace elements function as essential cofactors that are involved in various biochemical processes in mammals. Autophagy is vital for nutrient supplement, which is an important Zeitegber for the circadian homeostasis in heart. Here, we considered the possibility that autophagy, as well as the cardiomyocyte clock and glycolysis are interlinked. Detrimental effects were observed when cardiac system is exposed to bromine containing drugs. This study investigated the effects and mechanisms of bromide on the circadian clock and glycolytic metabolism of H9C2 cardiomyocytes. Results In the present study, bromide does not affect cell viability and apoptosis of H9C2 cardiomyocytes. Bromide dampens the clock and glycolytic (Hk2 and Pkm2) gene expression rhythmicity in a dose-dependent manner. Additionally, bromide inhibits autophagic process in H9C2 cardiomyocytes. In contrast, rapamycin (an autophagy inducer) dramatically restores the inhibitory effect of NaBr on the mRNA expression levels of clock genes (Bmal1, Cry1 and Rorα) and glycolytic genes (Hk2 and Pkm2). Conclusions Our results reveal that bromide represses the clock and glycolytic gene expression patterns, partially through inhibition of autophagy.

Additional file 6: Table S1. Calculations of Amplitude and Phase shift in Fig. 2. Table S2. Calculations of Amplitude and Phase shift in Fig. 3. Table S3. Calculations of Amplitude and Phase shift in Fig. 4. Table S4. The list of primer sequences for qPCR analysis.

Based on the free volume, shear transformation zone and percolation theory, a new percolation model has been established to investigate the ductile-brittle transition in amorphous alloys. Taking the binary Cu25Zr75 amorphous alloy for example, the influence of the free volume concentration and flow unit dispersity on its percolation threshold value was analyzed. The results show that the concentration of flow units reach a critical value when the ductile-brittle transition occurs in the Cu25Zr75 amorphous alloy, and this critical value is independent of the concentration of the free volume but dependent on the dispersity of flow units. Furthermore, the percolation threshold values of La-, Zr-, Cu-, Pd-, Fe-, Sr- and Tm-based amorphous alloys were also calculated, a percolation threshold value of ~0.516 for ductile-brittle transition in these amorphous alloys was obtained. Therefore, our analysis results suggest that ~0.516 appears to be a universal percolation threshold value for ductile-brittle transition in amorphous alloys.

The fuel assembly is the core component of the nuclear energy system, and its excessive deformation will affect the normal insertion of the fuel rod and endanger safe operation of the reactor. In this paper, we present an underwater fuel assembly deformation measurement system based on 10 sets of visual measurement units. Benefitting from the waterproof design, the shielding-radiation design, the reflective structure design, the dual-optical line laser triangulation principle, and the underwater multilayer refractive geometry, the measurement system has shorter measurement time, higher measurement accuracy, and better environmental adaptability. Through the underwater field measurement and verification of the standard rod and fuel assembly, the bow deformation measurement accuracy of the measurement system is better than 0.3 mm, and the twist deformation measurement accuracy of the system is better than 0.15°. The proposed method allows transient and high-precision measurement in a certain irradiation dose and certain depth water, which provides a strong guarantee for measurement of fuel assembly deformation parameters in deep water and high radiation.

Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells. Here we show that long-lived memory CD8 T cells are derived from a subset of effector T cells through a process of dedifferentiation. To assess the developmental origin of memory CD8 T cells, we investigated changes in DNA methylation programming at naive and effector cell-associated genes in virus-specific CD8 T cells during acute lymphocytic choriomeningitis virus infection in mice. Methylation profiling of terminal effector versus memory-precursor CD8 T cell subsets showed that, rather than retaining a naive epigenetic state, the subset of cells that gives rise to memory cells acquired de novo DNA methylation programs at naive-associated genes and became demethylated at the loci of classically defined effector molecules. Conditional deletion of the de novo methyltransferase Dnmt3a at an early stage of effector differentiation resulted in reduced methylation and faster re-expression of naive-associated genes, thereby accelerating the development of memory cells. Longitudinal phenotypic and epigenetic characterization of the memory-precursor effector subset of virus-specific CD8 T cells transferred into antigen-free mice revealed that differentiation to memory cells was coupled to erasure of de novo methylation programs and re-expression of naive-associated genes. Thus, epigenetic repression of naive-associated genes in effector CD8 T cells can be reversed in cells that develop into long-lived memory CD8 T cells while key effector genes remain demethylated, demonstrating that memory T cells arise from a subset of fate-permissive effector T cells.

To improve the performance of organic Rankine cycle (ORC) system, this paper proposes to replace the electric working fluid pump with multi-stage gas-liquid booster pump which is driven by high pressure gas generated in evaporator of ORC system. This pump consists of four gas-liquid booster pumps. The working principle of gas-liquid booster pump and multi-stage gas-liquid booster pump are introduced respectively. By using high pressure air as driving force and water as pressurized working fluid, the performance of multi-stage gas-liquid booster pump is tested experimentally. The experimental results of this study mainly consist of two parts: the first part focuses on the pump performance with various pressure at pump inlet and outlet while valve at pump inlet is completely open; the second part focuses on various valve open ratio at pump inlet which is operated at fixed inlet and outlet pressure of 1.8 MPa and 0.15 MPa. The results show that the pump conversion efficiency decreases with the increase of inlet pressure and the decrease of outlet pressure. The maximum conversion efficiency, volume flow rate of water and volume flow rate of high pressure air are 0.72, 0.55 L/s and 0.42 L/s respectively. When the pump is operated at different valve open ratio, the volume flow rate of water and high pressure air decreases with the decrement of valve open ratio. In addition, the conversion efficiency almost maintains identical under different valve open ratio.

The experimental and theoretical researches have been carried out to get the flow boiling heat transfer characteristics of carbon dioxide (CO2 or R744) as a refrigerant in horizontal mini-channel. Based on infrared thermal imaging tests and experimental studies on heat transfer coefficients, the heat transfer coefficients and dryout characteristics of CO2 are analyzed qualitatively and quantitatively in following conditions: Heat flux: 2~35 kW m-2, Mass flux: 50~1350 kg m-2 s-1, saturation temperature: −10~15 °C, mini-channel inner diameter: 1 mm and 2 mm. Primary conclusions can be drawn from the results of the experiments: The increase of heat flux enhances the nucleate boiling heat transfer of the refrigerant inside mini-channel, which leads to the remarkable increase of heat transfer coefficient. But it speeds up the process of dryout. It also has a certain influence on vapor qualities of dryout at both the starting and the ending stage. The effect of mass flux on heat transfer enhancement depends on the dominant heat transfer mode in the tube. With the increase of mass flow rate, the vapor quality at the start of dryout has a decreasing trend. But the heat transfer coefficient increases at the end of dryout process or even after dryout process; the heat transfer coefficient does not vary monotonically with the saturation temperature: when the saturation temperature is high and even close to CO2's critical temperature, the heat transfer coefficient increases with the increase of saturation temperature; when the saturation temperature is low, the heat transfer coefficient increases with the decrease of saturation temperature. Besides, during the heat transfer process, the dryout vapor quality falls monotonically with the increase of saturation temperature. It is reasonable to conclude that dryout characteristics have significant influence on heat transfer coefficient. Fang correlation that predicts the heat transfer coefficient of CO2 is in good agreement with the experimental data, which has a mean absolute deviation of 15.7%, and predicts 71.98% of the entire database within ±20% and 86.84% of the entire database within ±30%.

This paper presents an experimental and theoretical investigation on two-phase flow boiling heat transfer with carbon dioxide (CO 2 or R744) as the refrigerant in horizontal small diameter tube at low temperature. The experimental data were obtained in the following condition, the heat flux is 7.5–30 kW/m 2 ; the mass flow rate is 300–600 kg/m 2 s; the saturation temperature is 233–273 K; the test section is made of stainless steel tubes whose inner diameters are 0.6 and 1.5 mm. The experimental results show that heat transfer coefficient increases with the increase of mass flow rate, but decreases with the increase of tubes’ inner diameter and saturation temperature, the boiling heat transfer of CO 2 has a greater effect on nucleate boiling and highly depends on heat flux. The comparative study indicates that: during the existed flow boiling heat transfer model, the model which has the best prediction accuracy presented with 79.8% of predicted points within ±30% and 21.8% mean deviation before the dryout phenomenon happened, while it was only 18.4% and 59.9% after the dryout phenomenon happened.

The heat and mass transfer characteristics for fin-and-tube heat exchangers with low environmental pressures have been experimentally investigated. The variation trends of the jhjh factor, jmjm factor and Lewis factor were examined in this study when environmental pressure decreases from 101.3 to 40 kPa. The errors caused by non-unit Lewis factor when calculating the total heat transfer rate using the logarithmic mean enthalpy difference (LMED) method were discussed. It was found that the inlet humidity ratio for the incoming air is inversely proportional to environmental pressure under the experimental conditions. Both the heat and mass transfer performances decrease when the environmental pressure is reduced. However, the jmjm factor shows a transient rise when Re

The interactions between host and pathogen is exceedingly complex, which involves alterations at multiple molecular layers. However, research to simultaneously monitor the alterations of transcriptome and proteome between a bacterial pathogen and aquatic animal host through integrated dual RNA-seq and dual iTRAQ of tissue during infection is currently lacking. The important role of a diguanylate cyclase gene (L321_RS15240) in pathogenicity of Pseudomonas plecoglossicida against Epinephelus coioides was suggested by previous dual RNA-seq of our lab. Then L321_RS15240-RNAi strains of P. plecoglossicida were constructed with pCM130/tac, and the mutant with the best silencing effect was selected for follow-up study. The RNAi of L321_RS15240 resulted in a significant decrease in bacterial virulence of P. plecoglossicida. The E. coioides spleens infected by wild type strain or L321_RS15240-RNAi strain of P. plecoglossicida were subjected to dual RNA-seq and dual iTRAQ, respectively. The results showed that: RNAi of L321_RS15240 led to 1)alterations of host transcriptome associated with complement and coagulation cascades, ribosome, arginine and proline metabolism, and oxidative phosphorylation; 2)high expression of host proteins which related to phagosome and metabolism responses (metabolism of glutathione, amino sugar and nucleotide sugar); 3)the highly differentially expression of host lncRNAs and miRNAs. The differentially expressed proteins and mRNAs of pathogen were different after infection, but the functions of these proteins and mRNAs were mainly related to metabolism and virulence. This study provides a new insight to comprehensively understand the gene functions of pathogens and hosts at multiple molecular layers during in vivo infection.

In the present study, Larimichthys crocea and Pseudomonas plecoglossicida were selected as a host-pathogen interaction model for teleosts and prokaryotic pathogens. Five shRNAs were designed and synthesized to silence the fliA gene, all of which resulted in pronounced reductions in fliA mRNA, the mutant strain with the best silencing efficiency of 92.16% was chosen for subsequent analysis. A significant decrease in motility, intracellular survival and escape was observed for the fliA-RNAi strain of P. plecoglossicida, whereby silencing of the fliA gene led to a 30% decrease in mortality and a four-day delay in the onset of infection in L. crocea. Moreover, silencing of P. plecoglossicida fliA resulted in a significant change in both the pathogen and host transcriptome in the spleens of infected L. crocea. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of pathogen transcriptome data showed that silencing fliA resulted in downregulation of 18 flagellum-related genes, KEGG analysis of host transcriptome data revealed that infection with the fliA-RNAi strain caused upregulation of 47 and downregulation of 106 immune-related genes. These pathogen-host interactions might facilitate clearance of P. plecoglossicida by L. crocea, with a significant decrease in fliA-RNAi P. plecoglossicida strain virulence in L. crocea.