FAdV-4 can cause more noticeable clinical symptoms compared to FAdV-8b after infecting specific pathogen free chickens.

Chickens infected with FAdV-4 and FAdV-8b both exhibit hepatic lesions characterized by hemorrhagic necrosis and intranuclear inclusion body formation. However, only FAdV-4 induces pericardial effusion and acute mortality in chickens. To investigate the similarities and differences in the pathogenicity of HPS and IBH, this study intends to compare the infectivity and pathogenicity of FAdV-4 and FAdV-8b, 2 serotypes of fowl adenovirus isolated in our laboratory. The 2 viruses were respectively inoculated subcutaneously into SPF chicks at the neck. The clinical manifestations and pathological changes in these infected groups of chickens differed to some extent. Chickens infected with FAdV-4 exhibit evident depression and acute mortality, with a mortality rate of 60%; while those infected with FAdV-8b only display mild depression. Postmortem examination reveals serosanguinous effusion in the pericardial sac, spot-like hemorrhage, and focal necrosis in the liver of chickens infected with FAdV-4. Additionally, various degrees of edema are observed in organs such as the lungs, spleen, kidneys, and pancreas. In contrast, chickens infected with FAdV-8b exhibit spot-like hemorrhage and focal necrosis in the liver but do not display pericardial effusion or widespread organ edema. Histopathological examination demonstrates that both FAdV-4 and FAdV-8b can induce inflammatory reactions of varying degrees in the kidneys, pancreas, and duodenum of chickens, while reducing the necrosis of bursa of Fabricius, thymus, and spleen lymphocytes. Our data preliminarily reveal that both FAdV-4 and FAdV-8b can induce strong pathogenicity in chickens.

SzM protein of Streptococcus equi ssp. zooepidemicus triggers the release of neutrophil extracellular traps depending on GSDMD.

Streptococcus equissp.zooepidemicus (SEZ) is a crucial pathogen and contributes to various infections in numerous animal species. Swine streptococcicosis outbreak caused by SEZ has been reported in several countries in recent years. SzM protein is a cell membrane-anchored protein, which exhibits as an important virulence factor of SEZ. Effects of SzM protein on host innate immune need further study. Here, recombinant SzM (rSzM) protein of the SEZ was obtained, and mice were intraperitoneally injected with rSzM protein. We discovered that rSzM protein can recruit neutrophils into the injected site. In further study, neutrophils were isolated and treated with rSzM protein, NETs release were triggered by rSzM protein independently, and GSDMD protein was promoted-expressed and activated. In order to investigate the role of GSDMD in NETs formation, neutrophils isolated from WT mice and GSDMD-/- mice were treated with rSzM protein. The results showed that GSDMD deficiency suppressed the NETs release. In conclusion, SzM protein of SEZ can trigger the NETs release in a GSDMD-depending manner.

Air-ground coordinated unmanned swarm systems: A multitasking framework for control design.

An air-ground heterogeneous unmanned swarm system coordination is considered. The system consists of N unmanned aerial vehicles (UAVs) and one unmanned ground vehicle (UGV). This forms a complicated mission, which consists of the following four different tasks. First, the aerial vehicles are in a compact formation, while avoiding collision with each other. Second, the aerial vehicles should stay close to the ground, while avoiding collision with the ground. Third, the aerial vehicles should stay close to the ground vehicle. Fourth, the ground vehicle should follow a desired trajectory. These tasks reflect two seemingly contradictory nature: close to (due to tracking) and away from (due to avoidance). The effective control design should address all four tasks even in the presence of uncertainty. By two creative transformations, this multitude of tasks are consolidated in a χ-measure. An adaptive robust control, which includes a robust control scheme and an online adaptation law, is then proposed to render guarantee boundedness performance of this χ-measure. As a result, the control design is able to accomplish the combined tracking-avoidance mission for the uncertain swarm system. Despite the presence of conflicting aspects between these tasks, the designed controller exhibits outstanding performance.

SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination.

Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKKα/ß, subsequently leading to IRF3 and NF-κB phosphorylation. However, the specific E3 ubiquitin ligase for MDA5 K63-polyubiquitination has not been well characterized. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral immune agents indicates that SARS-CoV-2 escapes from antiviral immune responses via several unknown mechanisms. Here, we report that SARS-CoV-2 nonstructural protein 8 (nsp8) acts as a suppressor of antiviral innate immune and inflammatory responses to promote infection of SARS-CoV-2. It downregulates the expression of type I interferon, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and TRIM4 and impairing TRIM4-mediated MDA5 K63-linked polyubiquitination. Our findings reveal that nsp8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.

Facile fabrication of biocompatible injectable blended polymeric hydrogel with bioactive nanoformulation to improving cardiac tissue regeneration efficiency after myocardial infarction for nursing care potential applications.

Recent years, cardiac vascular disease has arisen owing to acute myocardial infarction (MI) and heart failure leading to death worldwide. Various treatments are available for MI in modern medicine such as implantation of devices, pharmaceutical therapy, and transplantation of organs, nonetheless, it has many complications in finding an organ donor, devices for stenosis, high intrusiveness and long-time hospitalization. To overcome these problems, we have designed and developed a novel hydrogel material with a combination of Se NPs loaded poly(ethylene glycol)/tannic acid (PEG/TA) hydrogel for the treatment of acute MI repair. Herein, Se NPs were characterized by effective analytical and spectroscopic techniques. In vitro cell compatibility and anti-oxidant analyses were examined on human cardiomyocytes in different concentrations of Se NPs and appropriate Se NPs loaded hydrogel samples to demonstrate its greater suitability for in vivo cardiac applications. In vivo investigations of MI mice models injected with Se hydrogels established that LV wall thickness was conserved significantly from the value of 235.6 µm to 390 µm. In addition, the relative scar thickness (33.6%) and infarct size (17.1%) of the MI model were enormously reduced after injection of Se hydrogel when compared to the Se NPs and control (MI) sample, respectively, which confirmed that Se introduced hydrogel have greatly influenced on the restoration of the infarcted heart. Based on the investigated results of the nanoformulation samples, it could be a promising material for future generations treatment of acute myocardial infarction and cardiac repair applications.

HighlightsDesign of novel combination of Se NPs loaded poly(ethylene glycol)/tannic acid conductive hydrogelThe prepared material provides favourable cell compatibility and anti-oxidant abilitiesHydrogel samples significantly influenced In vitro pro- and anti-inflammatory behavioursIt could be developed hydrogel promises of outstanding efficiency for the treatment of acute myocardial infarction.

Suppression of KSHV lytic replication and primary effusion lymphoma by selective RNF5 inhibition.

Primary effusion lymphoma (PEL), a rare aggressive B-cell lymphoma in immunosuppressed patients, is etiologically associated with oncogenic γ-herpesvirus infection. Chemotherapy is commonly used to treat PEL but usually results in poor prognosis and survival; thus, novel therapies and drug development are urgently needed for PEL treatment. Here, we demonstrated that inhibition of Ring finger protein 5 (RNF5), an ER-localized E3 ligase, suppresses multiple cellular pathways and lytic replication of Kaposi sarcoma-associated herpesvirus (KSHV) in PEL cells. RNF5 interacts with and induces Ephrin receptors A3 (EphA3) and EphA4 ubiquitination and degradation. RNF5 inhibition increases the levels of EphA3 and EphA4, thereby reducing ERK and Akt activation and KSHV lytic replication. RNF5 inhibition decreased PEL xenograft tumor growth and downregulated viral gene expression, cell cycle gene expression, and hedgehog signaling in xenograft tumors. Our study suggests that RNF5 plays the critical roles in KSHV lytic infection and tumorigenesis of primary effusion lymphoma.

Satellite Formation-Containment Control Emphasis on Collision Avoidance and Uncertainty Suppression.

This article explores an adaptive robust control scheme for satellite formation-containment flying in a way of constraint following. For safe flight and uncertainty suppression, both collision avoidance and uncertainty suppression are addressed. First, for uncertainty suppression, (possibly fast) time-varying but bounded uncertainty is considered, and then an adaptive law is proposed to estimate the comprehensive uncertainty bounds online. Second, the problem of formation-containment control with collision avoidance is converted into another problem of constraint-following control by taking the objectives of collision avoidance, formation, and containment, respectively, as the collision-avoidance constraint, formation constraint, and containment constraint. Third, an η -measure is introduced to gauge the constraint-following error, and then an adaptive robust control is proposed to render the error to be uniformly bounded and uniformly ultimately bounded, regardless of the uncertainty. By this, the satellites can follow the above collision-avoidance constraint, formation constraint, and containment constraint approximately. As a result, satellite formation-containment control emphasis on collision avoidance and uncertainty suppression is achieved.

Adaptive Robust Formation Control of Connected and Autonomous Vehicle Swarm System Based on Constraint Following.

This article proposes an adaptive robust formation control scheme for the connected and autonomous vehicle (CAV) swarm system by utilizing swarm property, diffeomorphism transformation, and constraint following. The control design is processed by starting from a 2-D dynamics model with (possibly fast) time varying but bounded uncertainty. The uncertainty bounds are unknown. For compact formation, the CAV system is treated as an artificial swarm system, for which the ideal swarm performance is taken as a desired constraint. By this, formation control is converted into a problem of constraint following and then a performance measure ß is defined as the control object to evaluate the constraint following error. For collision avoidance, a diffeomorphism transformation on space measure between two vehicles is creatively performed, by which the space measure is positive restricted. For uncertainty handling, an adaptive robust control scheme is proposed to render the ß -measure to be uniformly bounded and uniformly ultimately bounded, that is, drive the controlled (CAV) swarm system to follow the desired constraint approximatively. As a result, the system can achieve the ideal swarm performance; thereout, compact formation is realized, regardless of the uncertainty. The main contribution of this article is exploring a 2-D formation control scheme for (CAV) swarm system under the consideration of collision avoidance and time-varying uncertainty.

Subversion of autophagy machinery and organelle-specific autophagy by SARS-CoV-2 and coronaviruses.

As a new emerging severe coronavirus, the knowledge on the SARS-CoV-2 and COVID-19 remains very limited, whereas many concepts can be learned from the homologous coronaviruses. Macroautophagy/autophagy is finely regulated by SARS-CoV-2 infection and plays important roles in SARS-CoV-2 infection and pathogenesis. This review will explore the subversion and mechanism of the autophagy-related machinery, vacuoles and organelle-specific autophagy during infection of SARS-CoV-2 and coronaviruses to provide meaningful insights into the autophagy-related therapeutic strategies for infectious diseases of SARS-CoV-2 and coronaviruses.

Upregulation of ATF4-LAMP3 Axis by ORF45 Facilitates Lytic Replication of Kaposi's Sarcoma-Associated Herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a γ-oncogenic herpesvirus, and both lytic and latent infections play important roles in its pathogenesis and tumorigenic properties. Multiple cellular pathways and diverse mediators are hijacked by viral proteins and are used to support KSHV lytic replication. In previous studies, we revealed that KSHV ORF45 promoted KSHV transcription and translation by inducing sustained p90 ribosomal S6 kinase (RSK) activation and the phosphorylation of its substrates c-Fos and eIF4B. However, the cellular mediators required for lytic replication remain largely unknown. Here, we reveal that ORF45 activates eIF2α phosphorylation and ATF4 translation and then upregulates the expression of lysosome-associated membrane protein 3 (LAMP3) in an ATF4-dependent manner during KSHV lytic replication. Consequently, LAMP3 promotes Akt and ERK activation and then facilitates lytic gene expression and virion production. Furthermore, ATF4 enhances lytic replication through LAMP3, and LAMP3 acts in an ATF4-independent manner. Our findings suggest that the ATF4-LAMP3 axis is upregulated by ORF45 through ER stress activation during the KSHV lytic life cycle and, in turn, facilitates optimal lytic replication. IMPORTANCE The lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV) reprograms cellular transcription and translation to generate viral proteins and virion particles. Here, we show that the mediator of ER stress ATF4 and the expression of the downstream gene LAMP3 are upregulated by ORF45 during lytic replication. Consequently, increased LAMP3 expression activates Akt and ERK and promotes lytic replication. Although several UPR transcription factors are able to promote KSHV lytic replication, the proviral effect of ATF4 on lytic replication is attenuated by LAMP3 silencing, whereas the effect of LAMP3 does not directly require ATF4 expression, indicating that LAMP3 primarily exerts effects on KSHV lytic replication downstream of ATF4 and ER stress. Taken together, our findings suggest that the ORF45-upregulated ATF4-LAMP3 axis plays an essential role in KSHV lytic replication.

Seasonal source analysis of nitrogen and carbon aerosols of PM2.5 in typical cities of Zhejiang, China.

Fine particulate matter (PM2.5) significantly impacts global air quality and human health due to its smaller particle size and larger specific surface area. Nitrogen and carbon aerosols, as the main components of PM2.5, play key roles in air pollution. This study identified the sources and seasonal variation of nitrogen and carbon aerosols in PM2.5 in typical cities of Zhejiang. The annual average PM2.5 concentrations of Hangzhou (HZ), Ningbo (NB), and Huzhou (HUZ) were 39.8 ± 19.1 µg m-|3, 40.0 ± 21.5 µg m-3, and 50.1 ± 22.6 µg m-3, respectively, which exceeded the Chinese air quality limit of 35.0 µg m-3. The results showed that the concentrations of nitrogen aerosols (NO3- and NH4+) in water-soluble inorganic ions were higher at 9.6 ± 4.6 µg m-3, 9.0 ± 4.5 µg m-3 and 11.5 ± 5.4 µg m-3 in HZ, NB and HUZ, respectively, especially in winter, accounting for over 60% of the total. The annual average δ15N values of PM2.5 were 6.2 ± 1.9‰, 6.4 ± 2.2‰ and 6.7 ± 1.9‰ in HZ, NB and HZ, respectively; the δ15N values in winter were relatively low. A Bayesian isotopic mixing model was employed to analyse the sources of nitrogen aerosols in winter; the results showed that nitrogen concentration was mainly affected by NH3 and NOX emitted by motor vehicle exhaust, coal combustion, biomass combustion, biogenic soil emissions, animal wastes and ocean evaporation (NB). In addition, the carbon component analysis of PM2.5 showed that the annual average mass concentration of TC accounted for 18.7%, 16.4% and 20.1% of PM2.5 in HZ, HUZ and NB, respectively. The same isotope model was used to analyse the sources of carbon aerosols; the results showed that carbon aerosols were mainly affected by the sources of motor vehicle exhaust, coal combustion, biomass combustion and dust. In the PM2.5 in Zhejiang, the most contributory sources of nitrogenous aerosols and carbon aerosols were motor vehicle exhaust sources.

SARS-CoV-2 ORF3a induces RETREG1/FAM134B-dependent reticulophagy and triggers sequential ER stress and inflammatory responses during SARS-CoV-2 infection.

SARS-CoV-2 infections have resulted in a very large number of severe cases of COVID-19 and deaths worldwide. However, knowledge of SARS-CoV-2 infection, pathogenesis and therapy remains limited, emphasizing the urgent need for fundamental studies and drug development. Studies have shown that induction of macroautophagy/autophagy and hijacking of the autophagic machinery are essential for the infection and replication of SARS-CoV-2; however, the mechanism of this manipulation and the function of autophagy during SARS-CoV-2 infection remain unclear. In the present study, we identified ORF3a as an inducer of autophagy (in particular reticulophagy) and revealed that ORF3a localizes to the ER and induces RETREG1/FAM134B-related reticulophagy through the HMGB1-BECN1 (beclin 1) pathway. As a consequence, ORF3a induces ER stress and inflammatory responses through reticulophagy and then sensitizes cells to the acquisition of an ER stress-related early apoptotic phenotype and facilitates SARS-CoV-2 infection, suggesting that SARS-CoV-2 ORF3a hijacks reticulophagy and then disrupts ER homeostasis to induce ER stress and inflammatory responses during SARS-CoV-2 infection. These findings reveal the sequential induction of reticulophagy, ER stress and acute inflammatory responses during SARS-CoV-2 infection and imply the therapeutic potential of reticulophagy and ER stress-related drugs for COVID-19.Abbreviations: CQ: chloroquine; DEGs: differentially expressed genes; ER: endoplasmic reticulum; GSEA: gene set enrichment analysis; HMGB1: high mobility group box 1; HMOX1: heme oxygenase 1; MERS-CoV: Middle East respiratory syndrome coronavirus; RETREG1/FAM134B: reticulophagy regulator 1; RTN4: reticulon 4; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TN: tunicamycin.

Regulating Constraint-Following Bound for Fuzzy Mechanical Systems: Indirect Robust Control and Fuzzy Optimal Design.

This article proposes an optimal indirect approach of constraint-following control for fuzzy mechanical systems. The system contains (possibly fast) time-varying uncertainty that lies in a fuzzy set. It aims at an optimal controller for the system to render bounded constraint-following error such that it can stay within a predetermined bound at all time and be sufficiently small eventually. First, for deterministic performance, the original system is transformed into a constructed system. A deterministic (not the usual IF-THEN rules-based) robust control is then designed for the constructed system to render it to be uniformly bounded and uniformly ultimately bounded, regardless of the uncertainty. Second, for optimal performance, a performance index, including the average fuzzy system performance and control effort, is proposed based on the fuzzy information. An optimal design problem associated with the control gain is then formulated and solved by minimizing the performance index. Finally, it is proved when the constructed system renders uniform boundedness and uniform ultimate boundedness, the original system achieves the desired performance of bounded constraint following.

Robust Pointing Control of Marching Tank Gun With Matched and Mismatched Uncertainty.

This article focuses on a robust control scheme for pointing control of the marching tank gun. Both matched and mismatched uncertainties, which may be nonlinear (possibly fast) time varying but bounded, are considered. First, the pointing control system is constructed as a coupled, nonlinear, and uncertain dynamical system with two interconnected (horizontal and vertical) subsystems. Second, for the horizontal pointing control, robust control is proposed to render the horizontal subsystem to be practically stable. Third, for the vertical pointing control, an uncertainty bound-based state transformation is constructed in a similar way of backstepping to convert the original mismatched system (i.e., the vertical subsystem) to be locally matched and then robust control is proposed to render the transformed system to be practically stable. Finally, it is proved that when the transformed system is rendered to be practically stable, the original system renders the same performance; therefore, vertical pointing control is achieved. This work should be among the first ever endeavor to cast all the coupling, nonlinearity, and (both matched and mismatched) uncertainty into the pointing control framework of the marching tank gun.

BRLF1-dependent viral and cellular transcriptomes and transcriptional regulation during EBV primary infection in B lymphoma cells.

The immediate-early protein BRLF1 plays important roles in lytic infection of Epstein-Barr virus (EBV), in which it activates lytic viral transcription and replication. However, knowledge of the influence of BRLF1 on cellular gene expression and transcriptional reprogramming during the early lytic cycle remains limited. In the present study, deep RNA-sequencing analysis identified all differentially expressed genes (DEGs) and alternative splicing in B lymphoma cells subjected to wild-type and BRLF1-deficient EBV primary infection. The BRLF1-dependent cellular DEGs were annotated, and major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory responses, cytokine-receptor interactions and chemokine signaling and metabolic processes. Furthermore, analysis of BRLF1-binding proteins by mass spectrometry shows that BRLF1 binds to and cooperates with several transcription factors and components of the spliceosome and then influences both RNA polymerase II-dependent transcription and pre-mRNA splicing. The RTA-binding RRE motifs or specific motifs of unique cooperative transcription factors in viral and cellular DEG promoter regions indicate that BRLF1 employs different strategies for regulating viral and cellular transcription. Thus, our study characterized BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the comprehensive virus-cell interaction and alterations of transcription during EBV primary infection and lytic replication.

Genotypic evolution and epidemiological characteristics of H9N2 influenza virus in Shandong Province, China.

H9N2 avian influenza has been prevalent in chicken flocks of China for years. In the first half year of 2018, clinical cases of suspected H9N2 infection were collected from chicken flocks in Shandong province. Nine strains of H9N2 influenza virus were isolated. The pathological changes of the dead chickens were mainly respiratory inflammation, renal swelling, and secondary infection. The microscopic lesions were consistent with the pathogenic characteristics of H9N2 influenza virus. From November 2017 to June 2018, a total of 3,380 serum samples were randomly collected from commercial laying hens in Shandong Province. The H9 antibody levels were tested with the isolated strain (CK/SD/231/17) as the antigen. It showed that the average of antibody titers of H9 avian influenza was 9.24 1og2. Hemagglutination inhibition experiments were conducted on chicken serum with the vaccine virus and the isolated virus (CK/SD/231/17) as the antigens. It was found that the antibody titer measured with the vaccine virus was 1 or 2 titers higher than the isolated strain. It indicated that the antigenicity of H9N2 circulating strain was different from that of vaccine strain. The nucleotide sequences of HA gene of these recent H9N2 avian influenza virus isolates shared homologies from 93.8 to 99.9%. Phylogenetic analysis revealed that the eight gene segments of the viruses were in the same clades with G57 gene reference strain. The amino acid site analysis of influenza resistance showed that the virus was sensitive to neuraminidase inhibitors and resistant to amantadine. Highlights: The protection rate of the H9N2 AIV vaccine almost reached 100% before 2016, but the antibody level of serum samples showed high diversity in this study, which means the poultry were infected. The antigenicity of isolated H9N2 strains was different from that of vaccine strain. Current available vaccines may provide only limited protection.

Immunosuppressive potential of fowl adenovirus serotype 4.

Fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium syndrome. To clarify the effects of FAdV-4 on immune organs in birds, we conducted a detailed examination of dynamic morphology and damage mechanisms in chickens randomly divided into 4 groups (FAdV-4, vaccination, FAdV-4 plus vaccination, and control). FAdV-4 caused the depletion of lymphocytes and subsequent growth impairment in the thymus and bursa. Chickens infected with FAdV-4 and subjected to vaccination experienced greater inhibition of antibody responses to inactivated vaccines against Newcastle disease and avian influenza virus subtype H9 than uninfected and vaccinated chickens. The mechanisms underlying adenovirus-mediated lymphoid organ damage were further investigated via transferase-mediated dUTP nick-end labeling and apoptotic genes transcription analyses. Notably, lymphocytes apoptosis in lymphoid organs and expression of specific gene transcripts was significantly upregulated after infection (P < 0.05). Furthermore, increased expression of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α mRNA was observed (P < 0.05), compared to the control group. Our collective findings suggested that FAdV-4 caused structural and functional damage of immune organs via apoptosis along with induction of a severe inflammatory response.

Difference in pathogenicity of 2 strains of avian leukosis virus subgroup J in broiler chicken.

Avian leukosis virus subgroup J has been found to infect many types of chickens with various genetic backgrounds. The ALV-J strain NX0101, which was isolated from broiler breeders in 2001, mainly induces the formation of myeloid cell tumors. However, strain HN10PY01, which was recently isolated from laying hens, mainly induces the formation of myeloid cell tumors and hemangioma. In order to determine the difference in pathogenicity of the 2 strains in broiler chickens, 2 groups of chicken embryos were infected with NA0101 and HN10PY01 separately. A comparison was made of the mortality, oncogenicity, body weights, indexes for immune organs, levels of ALV group-specific antigen p27, and mRNA expression levels of the tumor-related gene, p53, in ALV-J-infected birds and immune organs of theses chickens in response to Newcastle Disease Virus (NDV) and avian influenza virus subtype H9 (AIV-H9) vaccination. The results indicated that strain NX0101 was highly pathogenic in broiler chickens and led to a 30% mortality rate and 45% oncogenicity, compared with the HN10PY01-infected birds. Weight of chickens was also significantly lower after 15 wk (P < 0.05). In addition, the mRNA expression levels of tumor-related p53 in medulla, liver, and lung in broilers infected with strain NX0101 were significantly higher than those infected with strain HN10PY01 (P < 0.05). These results indicated that strain NX0101 had a higher replication ability in broiler chickens. The findings of this study will contribute to further elucidating the mechanisms underlying host susceptibility and tumor classification in ALV-J-infected chickens.

Mechanism of fowl adenovirus serotype 4-induced heart damage and formation of pericardial effusion.

Fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium syndrome (HPS), which is characterized by the accumulation of a clear, straw-colored fluid in the pericardial sac, and high mortality rates. In order to explore the mechanism of FAdV-4-induced cardiac damage, dynamic pathology, apoptosis, and inflammatory reactions were analyzed in vivo. Moreover, we detected viral proliferation, and ultrastructure, inflammation and apoptosis of cardiomyocytes (CM) after FAdV-4 infection in vitro. The results showed that FAdV-4 impaired cardiac integrity and function by causing apoptosis and inflammation in vivo. Flow cytometry showed that CM infected with FAdV-4 did not show apoptosis in vitro. In addition, the mRNA expression of four inflammatory cytokines (interleukin (il)1B, il6, il8, and tumor necrosis factor), and activity of three myocardial enzymes were significantly different between FAdV-4 and control groups. However, in vitro, these indexes showed no significant difference between the groups. These observations collectively indicated that the heart was not the target organ of FAdV-4, and the virus may not directly lead to the occurrence of CM apoptosis and inflammation. To explore the source of pericardial effusion, we measured total protein, albumin, aspartate aminotransferase, creatine kinase isoenzyme, lactate dehydrogenase, potassium, sodium, and chloride ions in serum and pericardial effusion. Pericardial effusion was derived from vascular exudation rather than CM degeneration. Further studies are needed to investigate the exudation mechanism of vascular endothelial cells in FAdV-4 infection then weakened or eliminated pericardial effusion to minimize heart injury and/or restore damaged CM.

LncRNA LINC00319 accelerates ovarian cancer progression through miR-423-5p/NACC1 pathway.

Long noncoding RNA (lncRNA) LINC00319 has been reported to promote carcinogenesis of lung cancer and cutaneous squamous cell carcinoma. However, the role and mechanism of LINC00319 in ovarian cancer progression is unclear. In this study, LINC00319 expression was found to be upregulated in ovarian cancer tissues and cell lines. And our evidence showed that LINC00319 could be a potential prognostic biomarker for patients with ovarian cancer. Cell Counting Kit-8 (CCK-8), colony formation and transwell assays indicated that LINC00319 upregulation promoted proliferation, migration and invasion of ovarian cancer cells. Bioinformatics analysis and luciferase reporter assay revealed that LINC00319 worked as the sponge for miR-423-5p. Furthermore, miR-423-5p directly targeted NACC1. qRT-PCR and western blot results demonstrated that LINC00319 upregulates NACC1 expression through inhibiting miR-423-5p in ovarian cancer cells. Moreover, we observed an inverse expression correlation between miR-423-5p and LINC00319 or between miR-423-5p and NACC1 in ovarian cancer tissues. Finally, rescue assay showed that NACC1 restoration rescued the potentials of proliferation, migration and invasion in LINC00319-depleted ovarian cancer cells. In conclusion, our findings demonstrated that LINC00319 promotes ovarian cancer progression through upregulating NACC1 expression by restraining miR-423-5p.