"Floating Catalytic Foam" with prominent heat-induced convection for the effective photocatalytic removal of antibiotics.

Immobilized photocatalysts represent a promising candidate for the wastewater treatments due to their good reusability, high stability and low eco-risk. Mass transfer within the immobilized catalytic bed is a crucial process that determines the contacting, adsorption, and degradation kinetics in the photodegradation. In this study, a floating catalytic foam (FCF) with a prominent pumping effect was designed to promote mass transfer. The polyurethane foam immobilized with rGO/TiO2/ultrathin-g-C3N4 photocatalyst (PRTCN) was prepared by a simple dip-coating and Uv-light aging process. It was found that the hydrophilic-hydrophobic interfaces could not only contribute to the floating of the catalyst but also establish a temperature gradient across the floating immobilized catalyst. In addition, the temperature gradient induced convection could serve as a built-in pump to effectively promote the diffusion and adsorption of target antibiotic molecules during the photocatalytic process. Therefore, the PRTCN demonstrated a high photodegradation and mineralization efficiency with excellent reusability and anti-interference capability. Moreover, the photodegradation mechanism and the intermediates' toxicity of norfloxacin were detailly investigated by ultra-high resolution electrospray time-of-flight mass spectrometry, density functional theory simulation and ECOSAR estimation. This work proposed a facile and sustainable strategy to enhance the mass transfer problem on immobilized photocatalysts, which could promote the application of the immobilized photocatalysts in the real water-treatment scenarios.

Atomically dispersed Fe-O4-C sites as efficient electrocatalysts for electrosynthesis of hydrogen peroxide.

The electrochemical reduction of oxygen via the 2e pathway is an environmentally friendly approach to the electrosynthesis of H2O2. Nevertheless, its sluggish kinetics and limited selectivity hinder its practical application. Herein, single Fe atoms anchored on graphene oxide (SA Fe/GO) with Fe-O4-C sites are developed as an efficient electrocatalyst for the electro-synthesis of H2O2. These Fe-O4-C site active centres could efficiently enhance the activity and selectivity towards 2e electrochemical oxygen reduction in an alkaline environment. The newly-developed SA Fe/GO electrocatalyst demonstrates exceptional electrochemical performance, exhibiting impressive activity with an onset potential of 0.90 and H2O2 production of 0.60 mg cm-2 h-1 at 0.4 V. Remarkably, it achieves a remarkable H2O2 selectivity of over 95.5%.

A novel slow-release selenium approach for cadmium reduction and selenium enrichment in rice (Oryza sativa L.).

In this study, a novel slightly-soluble selenium (Se) fertilizer (SSF) was successfully applied to address the problems of Cd pollution in paddy soil and rice, and Se deficiency in human beings. The pot and field experiments showed that Cd content in the rice grains was reduced by 48.4%-82.89% and Se content was increased nearly by 30-fold comparing the control group. The application of SSF increased the soil pH and significantly reduced the DGT-extracted Cd in the soil. Moreover, DCB-extractable Fe content on the surface of roots was prompt by SSF, which formed a physical barrier, namely iron plaque (IP), to inhibit Cd translocation to the above-ground tissues of the rice plants. The Cd content in the IP was also decreased before the filling period, possibly contributing to the reduction in major Cd accumulation in the rice grains. In addition, the continuous Se increase and Cd reduction in the IP by the SSF gradually exceeded that of water-soluble Se during the three periods of rice plant growth. This suggests that SSF has high potential to be an effective Se fertilizer for inhibiting Cd uptake and enriching Se in rice.

(Na, Pb)-Jarosite nucleation and growth on anglesite: Implications for inhibition of Pb releasing.

The mobility and bioavailability of Pb can be significantly reduced by Pb-bearing minerals encapsulation in jarosite-group minerals, especially in sulfate-rich environments. However, the kinetic pathways and mechanisms of jarosite-group minerals formations on Pb-bearing mineral surfaces are not well understood. Here, time-resolved heterogeneous (Na, Pb)-jarosite nucleation and growth on anglesite were explored to gain insights into the encapsulation mechanisms. The initial dissolution of anglesite were clearly distinguished, and for the first time, the facet-specific heterogeneous nucleation of (Na, Pb)-jarosite on anglesite was demonstrated. Density functional theory calculations revealed higher adsorption energies and electronic interactions of FeSO4+ complex on anglesite (020), (140), (110) facets, attributed to the preferential nucleation of (Na, Pb)-jarosite on these facets, which resulted in effective passivation of the facets resistant to dissolution. An interpretation was proposed where (Na, Pb)-jarosite grew via a particle-attachment pathway involving the formation of amorphous intermediate, and subsequently, it transformed to the crystalline phase by solid-state conversion. These observations might improve the mechanistic understanding of interface interactions between slightly soluble Pb-bearing minerals and iron minerals, with implications for Pb immobilization in sulfate-rich environments.

Alternatively activated lung alveolar and interstitial macrophages promote fungal growth.

How lung macrophages, especially interstitial macrophages (IMs), respond to invading pathogens remains elusive. Here, we show that mice exhibited a rapid and substantial expansion of macrophages, especially CX3CR1+ IMs, in the lung following infection with Cryptococcus neoformans, a pathogenic fungus leading to high mortality among patients with HIV/AIDS. The IM expansion correlated with enhanced CSF1 and IL-4 production and was affected by the deficiency of CCR2 or Nr4a1. Both alveolar macrophages (AMs) and IMs were observed to harbor C. neoformans and became alternatively activated following infection, with IMs being more polarized. The absence of AMs by genetically disrupting CSF2 signaling reduced fungal loads in the lung and prolonged the survival of infected mice. Likewise, infected mice depleted of IMs by the CSF1 receptor inhibitor PLX5622 displayed significantly lower pulmonary fungal burdens. Thus, C. neoformans infection induces alternative activation of both AMs and IMs, which facilitates fungal growth in the lung.

Chicken CH25H inhibits ALV-J replication by promoting cellular autophagy.

Autophagy plays an important role in host antiviral defense. The avian leukosis virus subgroup J (ALV-J) has been shown to inhibit autophagy while promoting viral replication. The underlying autophagic mechanisms, however, are unknown. Cholesterol 25-hydroxylase (CH25H) is a conserved interferon-stimulated gene, which converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol (25HC). In this study, we further investigated the autophagic mechanism of CH25H resistance to ALV-J in chicken embryonic fibroblast cell lines (DF1). Our results found that overexpression of CH25H and treatment with 25HC promoted the autophagic markers microtubule-associated protein 1 light chain 3 II (LC3II) and autophagy-related gene 5(ATG5), while decreased autophagy substrate p62/SQSTM1 (p62) expression in ALV-J infection DF-1 cells. Induction of cellular autophagy also reduces the levels of ALV-J gp85 and p27. ALV-J infection, on the other hand, suppresses autophagic marker protein LC3II expression. These findings suggest that CH25H-induced autophagy is a host defense mechanism that aids in ALV-J replication inhibition. In particular, CH25H interacts with CHMP4B and inhibits ALV-J infection in DF-1 cells by promoting autophagy, revealing a novel mechanism by which CH25H inhibits ALV-J infection. Although the underlying mechanisms are not completely understood, CH25H and 25HC are the first to show inhibiting ALV-J infection via autophagy.

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Clinical Studies to Animal Experiments.

Cryptococcus neoformans is an encapsulated pathogenic fungus that initially infects the lung but can migrate to the central nervous system (CNS), resulting in meningoencephalitis. The organism causes the CNS infection primarily in immunocompromised individuals including HIV/AIDS patients, but also, rarely, in immunocompetent individuals. In HIV/AIDS patients, limited inflammation in the CNS, due to impaired cellular immunity, cannot efficiently clear a C. neoformans infection. Antiretroviral therapy (ART) can rapidly restore cellular immunity in HIV/AIDS patients. Paradoxically, ART induces an exaggerated inflammatory response, termed immune reconstitution inflammatory syndrome (IRIS), in some HIV/AIDS patients co-infected with C. neoformans. A similar excessive inflammation, referred to as post-infectious inflammatory response syndrome (PIIRS), is also frequently seen in previously healthy individuals suffering from cryptococcal meningoencephalitis. Cryptococcal IRIS and PIIRS are life-threatening complications that kill up to one-third of affected people. In this review, we summarize the inflammatory responses in the CNS during HIV-associated cryptococcal meningoencephalitis. We overview the current understanding of cryptococcal IRIS developed in HIV/AIDS patients and cryptococcal PIIRS occurring in HIV-uninfected individuals. We also describe currently available animal models that closely mimic aspects of cryptococcal IRIS observed in HIV/AIDS patients.

Cryptococcus neoformans Infection in the Central Nervous System: The Battle between Host and Pathogen.

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus with a global distribution. Humans become infected by inhaling the fungus from the environment, and the fungus initially colonizes the lungs. If the immune system fails to contain C. neoformans in the lungs, the fungus can disseminate to the blood and invade the central nervous system, resulting in fatal meningoencephalitis particularly in immunocompromised individuals including HIV/AIDS patients. Following brain invasion, C. neoformans will encounter host defenses involving resident as well as recruited immune cells in the brain. To overcome host defenses, C. neoformans possesses multiple virulence factors capable of modulating immune responses. The outcome of the interactions between the host and C. neoformans will determine the disease progression. In this review, we describe the current understanding of how C. neoformans migrates to the brain across the blood-brain barrier, and how the host immune system responds to the invading organism in the brain. We will also discuss the virulence factors that C. neoformans uses to modulate host immune responses.

Mechanisms of Pb(II) coprecipitation with natrojarosite and its behavior during acid dissolution.

Lead (Pb) coprecipitation with jarosite is common in natural and engineered environments, such as acid mine drainage (AMD) sites and hydrometallurgical industry. Despite the high relevance for environmental impact, few studies have examined the exact interaction of Pb with jarosite and the dissolution behavior of each phase. In the present work, we demonstrate that Pb mainly interacts with jarosite in four modes, namely incorporation, occlusion, physically mixing, and chemically mixing. For comparison, the four modes of Pb-bearing natrojarosite were synthesized and characterized separately. Batch dissolution experiments were undertaken on these synthetic Pb-bearing natrojarosites under pH 2 to simulate the AMD environments. The introduction of Pb decreases the final Fe releasing efficiency of jarosite-type compounds from 18.18% to 3.45%-5.01%, showing a remarkable inhibition of their dissolution. For Pb releasing behavior, PbSO4 dissolves in preference to Pb-substituted natrojarosite, i.e., (Na, Pb)-jarosite, which primarily results in the sharp increase of Pb releasing concentration (> 40 mg/L). PbSO4 occlusion by jarosite-type compounds can significantly reduce the release of Pb. The results of this study could provide useful information regarding Fe and Pb cycling in acidic natural and engineered environments.

Growth hormone receptor gene influences mitochondrial function and chicken lipid metabolism by AMPK-PGC1α-PPAR signaling pathway.

BACKGROUND: Adipose tissue is an important endocrine and energy-storage organ in organisms, and it plays a crucial role in the energy-metabolism balance. Previous studies have found that sex-linked dwarf (SLD) chickens generally have excessively high abdominal fat deposition during the growing period, which increases feeding costs. However, the underlying mechanism of this fat deposition during the growth of SLD chickens remains unknown. RESULTS: The Oil Red O staining showed that the lipid-droplet area of SLD chickens was larger than that of normal chickens in E15 and 14d. Consistently, TG content in the livers of SLD chickens was higher than that of normal chickens in E15 and 14d. Further, lower ΔΨm and lower ATP levels and higher MDA levels were observed in SLD chickens than normal chickens in both E15 and 14d. We also found that overexpression of GHR reduced the expression of genes related to lipid metabolism (AMPK, PGC1α, PPARγ, FAS, C/EBP) and oxidative phosphorylation (CYTB, CYTC, COX1, ATP), as well as reducing ΔΨm and ATP levels and increasing MDA levels. In addition, overexpression of GHR inhibited fat deposition in CPPAs, as measured by Oil Red O staining. On the contrary, knockdown of GHR had the opposite effects in vitro. CONCLUSIONS: In summary, we demonstrate that GHR promotes mitochondrial function and inhibits lipid peroxidation as well as fat deposition in vivo and in vitro. Therefore, GHR is essential for maintaining the stability of lipid metabolism and regulating mitochondrial function in chicken.

dPRLR causes differences in immune responses between early and late feathering chickens after ALV-J infection.

To understand the differences in immune responses between early feathering (EF) and late feathering (LF) chickens after infection with avian leukosis virus, subgroup J (ALV-J), we monitored the levels of prolactin, growth hormone and the immunoglobulins IgG and IgM in the serum of LF and EF chickens for 8 weeks. Moreover, we analysed the expression of immune-related genes in the spleen and the expression of PRLR, SPEF2 and dPRLR in the immune organs and DF-1 cells by qRT-PCR. The results showed that ALV-J infection affected the expression of prolactin, growth hormone, IgG and IgM in the serum. Regardless of whether LF and EF chickens were infected with ALV-J, the serum levels of the two hormones and two immunoglobulins in EF chickens were higher than those in LF chickens (P < 0.05). However, the expression of immune-related genes in the spleen of positive LF chickens was higher than that in the spleen of positive EF chickens. In the four immune organs, PRLR and SPEF2 expression was also higher in LF chickens than in EF chickens. Furthermore, the dPRLR expression of positive LF chickens was higher than that of negative LF chickens. After infection with ALV-J, the expression of PRLR in DF-1 cells significantly increased. In addition, overexpression of PRLR or dPRLR in DF-1 cells promoted replication of ALV-J. These results suggested that the susceptibility of LF chickens to ALV-J might be induced by dPRLR.

IL-27 Signaling Promotes Th1 Responses and Is Required to Inhibit Fungal Growth in the Lung during Repeated Exposure to Aspergillus fumigatus.

Aspergillus fumigatus is an opportunistic fungal pathogen that causes a wide spectrum of diseases in humans, including life-threatening invasive infections as well as several hypersensitivity respiratory disorders. Disease prevention is predicated on the host's ability to clear A. fumigatus from the lung while also limiting inflammation and preventing allergic responses. IL-27 is an important immunoregulatory cytokine, but its role during A. fumigatus infection remains poorly understood. In contrast to most infection settings demonstrating that IL-27 is anti-inflammatory, in this study we report that this cytokine plays a proinflammatory role in mice repeatedly infected with A. fumigatus We found that mice exposed to A. fumigatus had significantly enhanced secretion of IL-27 in their lungs. Genetic ablation of IL-27Rα in mice resulted in significantly higher fungal burdens in the lung during infection. The increased fungal growth in IL-27Rα-/- mice was associated with reduced secretion of IL-12, TNF-α, and IFN-γ, diminished T-bet expression, as well as a reduction in CD4+ T cells and their activation in the lung, demonstrating that IL-27 signaling promotes Th1 immune responses during repeated exposure to A. fumigatus In addition, infected IL-27Rα-/- mice displayed reduced accumulation of dendritic cells and exudate macrophages in their lungs, and these cells had a lower expression of MHC class II. Collectively, this study suggests that IL-27 drives type 1 immunity and is indispensable for inhibiting fungal growth in the lungs of mice repeatedly exposed to A. fumigatus, highlighting a protective role for this cytokine during fungal infection.

CXCR6+CD4+ T cells promote mortality during Trypanosoma brucei infection.

Liver macrophages internalize circulating bloodborne parasites. It remains poorly understood how this process affects the fate of the macrophages and T cell responses in the liver. Here, we report that infection by Trypanosoma brucei induced depletion of macrophages in the liver, leading to the repopulation of CXCL16-secreting intrahepatic macrophages, associated with substantial accumulation of CXCR6+CD4+ T cells in the liver. Interestingly, disruption of CXCR6 signaling did not affect control of the parasitemia, but significantly enhanced the survival of infected mice, associated with reduced inflammation and liver injury. Infected CXCR6 deficient mice displayed a reduced accumulation of CD4+ T cells in the liver; adoptive transfer experiments suggested that the reduction of CD4+ T cells in the liver was attributed to a cell intrinsic property of CXCR6 deficient CD4+ T cells. Importantly, infected CXCR6 deficient mice receiving wild-type CD4+ T cells survived significantly shorter than those receiving CXCR6 deficient CD4+ T cells, demonstrating that CXCR6+CD4+ T cells promote the mortality. We conclude that infection of T. brucei leads to depletion and repopulation of liver macrophages, associated with a substantial influx of CXCR6+CD4+ T cells that mediates mortality.

SOCS3 Promotes ALV-J Virus Replication via Inhibiting JAK2/STAT3 Phosphorylation During Infection.

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that causes immunosuppression and neoplastic diseases in poultry. Cytokine signal-transduction inhibitor molecule 3 (SOCS3) is an important negative regulator of the JAK2/STAT3 signaling pathway and plays certain roles in ALV-J infection. It is of significance to confirm the roles of SOCS3 in ALV-J infection and study how this gene affects ALV-J infection. In this study, we assessed the expression of the SOCS3 gene in vivo and in vitro, and investigated the roles of SOCS3 in ALV-J infection using overexpressed or interfered assays with the SOCS3 in DF-1 cells. The results showed that the SOCS3 expression of ALV-J infected chickens was different from uninfected chickens in the spleen, thymus and cecal tonsil. Further, SOCS3 is mainly expressed in the nucleus as determined by immunofluorescence assay. Overexpression of SOCS3 in DF-1 cells promoted the replication of ALV-J virus, and the expression of interferons (IFNα and INFß), inflammatory factors (IL-6 and TNFα) along with interferon-stimulating genes (CH25H, MX1, OASL, and ZAP). Conversely, interference of SOCS3 showed the opposite results. We also observed that SOCS3 promoted ALV-J virus replication by inhibiting JAK2/STAT3 phosphorylation. In conclusion, SOCS3 promotes ALV-J replication via inhibiting the phosphorylation of the JAK2/STAT3 signaling pathway. These results would advance further understanding of the persistent infection and the viral immune evasion of the ALV-J virus.

FcRn-Targeted Mucosal Vaccination against Influenza Virus Infection.

The respiratory tract is constantly exposed to various airborne pathogens. Most vaccines against respiratory infections are designed for the parenteral routes of administration; consequently, they provide relatively minimal protection in the respiratory tract. A vaccination strategy that aims to induce the protective mucosal immune responses in the airway is urgently needed. The FcRn mediates IgG Ab transport across the epithelial cells lining the respiratory tract. By mimicking this natural IgG transfer, we tested whether FcRn delivers vaccine Ags to induce a protective immunity to respiratory infections. In this study, we designed a monomeric IgG Fc fused to influenza virus hemagglutinin (HA) Ag with a trimerization domain. The soluble trimeric HA-Fc were characterized by their binding with conformation-dependent HA Abs or FcRn. In wild-type, but not FcRn knockout, mice, intranasal immunization with HA-Fc plus CpG adjuvant conferred significant protection against lethal intranasal challenge with influenza A/PR/8/34 virus. Further, mice immunized with a mutant HA-Fc lacking FcRn binding sites or HA alone succumbed to lethal infection. Protection was attributed to high levels of neutralizing Abs, robust and long-lasting B and T cell responses, the presence of lung-resident memory T cells and bone marrow plasma cells, and a remarkable reduction of virus-induced lung inflammation. Our results demonstrate for the first time, to our knowledge, that FcRn can effectively deliver a trimeric viral vaccine Ag in the respiratory tract and elicit potent protection against respiratory infection. This study further supports a view that FcRn-mediated mucosal immunization is a platform for vaccine delivery against common respiratory pathogens.

Quantitative analysis reveals internalisation of Cryptococcus neoformans by brain endothelial cells in vivo.

Migration of Cryptococcus neoformans from the blood to the brain parenchyma is crucial to cause fatal meningoencephalitis. Although mechanisms involved in brain migration of C. neoformans have been widely studied in vitro, less is known about how the fungus crosses the blood-brain barrier (BBB) in vivo. This is in part because of the lack of an approach to quantitatively analyse the dynamics of fungal transmigration into the brain across the BBB in vivo. In this study, we report a novel approach to quantitatively analyse the interactions between C. neoformans and brain endothelial cells in a mouse model using flow cytometry. Using this system, we show that C. neoformans was internalised by brain endothelial cells in vivo and that mice infected with acapsular or heat-killed C. neoformans yeast cells displayed a lower frequency of brain endothelial cells containing the yeast cell compared to mice infected with wild-type or viable yeast cells, respectively. We further demonstrate that brain endothelial cells were invaded by serotype A strain (H99 strain) at a higher rate compared to serotype D strain (52D strain). Our experiments established that internalisation of C. neoformans by brain endothelial cells occurred in vivo and offered a powerful approach to quantitatively analyse fungal migration into the brain.

IL-27 Negatively Regulates Tip-DC Development during Infection.

Tumor necrosis factor (TNF)/inducible nitric oxide synthase (iNOS)-producing dendritic cells (Tip-DCs) have profound impacts on host immune responses during infections. The mechanisms regulating Tip-DC development remain largely unknown. Here, using a mouse model of infection with African trypanosomes, we show that a deficiency in interleukin-27 receptor (IL-27R) signaling results in escalated intrahepatic accumulation of Ly6C-positive (Ly6C+) monocytes and their differentiation into Tip-DCs. Blocking Tip-DC development significantly ameliorates liver injury and increases the survival of infected IL-27R-/- mice. Mechanistically, Ly6C+ monocyte differentiation into pathogenic Tip-DCs in infected IL-27R-/- mice is driven by a CD4+ T cell-interferon gamma (IFN-γ) axis via cell-intrinsic IFN-γ signaling. In parallel, hyperactive IFN-γ signaling induces cell death of Ly6C-negative (Ly6C-) monocytes in a cell-intrinsic manner, which in turn aggravates the development of pathogenic Tip-DCs due to the loss of the negative regulation of Ly6C- monocytes on Ly6C+ monocyte differentiation into Tip-DCs. Thus, IL-27 inhibits the dual-track exacerbation of Tip-DC development induced by a CD4+ T cell-IFN-γ axis. We conclude that IL-27 negatively regulates Tip-DC development by preventing the cell-intrinsic effects of IFN-γ and that the regulation involves CD4+ T cells and Ly6C- monocytes. Targeting IL-27 signaling may manipulate Tip-DC development for therapeutic intervention.IMPORTANCE TNF/iNOS-producing dendritic cells (Tip-DCs) are at the front line as immune effector cells to fight off a broad range of invading microbes. Excessive development of Tip-DCs contributes to tissue destruction. Thus, identifying master regulators of Tip-DC development is fundamental for developing new therapeutic strategies. Here, we identify Tip-DCs as a terminal target of IL-27, which prevents Tip-DC-mediated early mortality during parasitic infections. We demonstrate that IL-27 inhibits Tip-DC development via a dual-track mechanism involving the complex interactions of effector CD4+ T cells, Ly6C- monocytes, and Ly6C+ monocytes. These findings delineate an in-depth view of mechanisms of Tip-DC differentiation that may have significant implications for the ongoing development of IL-27-based immunotherapy.

High expression of BCL6 inhibits the differentiation and development of hematopoietic stem cells and affects the growth and development of chickens.

BACKGROUND: B-cell CLL/lymphoma 6 (BCL6) is a transcriptional master regulator that represses more than 1200 potential target genes. Our previous study showed that a decline in blood production in runting and stunting syndrome (RSS) affected sex-linked dwarf (SLD) chickens compared to SLD chickens. However, the association between BCL6 gene and hematopoietic function remains unknown in chickens. METHODS: In this study, we used RSS affected SLD (RSS-SLD) chickens, SLD chickens and normal chickens as research object and overexpression of BCL6 in hematopoietic stem cells (HSCs), to investigate the effect of the BCL6 on differentiation and development of HSCs. RESULTS: The results showed that comparison of RSS-SLD chickens with SLD chickens, the BCL6 was highly expressed in RSS-SLD chickens bone marrow. The bone marrow of RSS-SLD chickens was exhausted and red bone marrow was largely replaced by yellow bone marrow, bone density was reduced, and the levels of immature erythrocytes in peripheral blood were increased. At the same time, the hematopoietic function of HSCs decreased in RSS-SLD chickens, which was manifested by a decrease in the hematopoietic growth factors (HGFs) EPO, SCF, TPO, and IL-3, as well as hemoglobin α1 and hemoglobin ß expression. Moreover, mitochondrial function in the HSCs of RSS-SLD chickens was damaged, including an increase in ROS production, decrease in ATP concentration, and decrease in mitochondrial membrane potential (ΔΨm). The same results were also observed in SLD chickens compared with normal chickens; however, the symptoms were more serious in RSS-SLD chickens. Additionally, after overexpression of the BCL6 in primary HSCs, the secretion of HGFs (EPO, SCF, TPO and IL-3) was inhibited and the expression of hemoglobin α1 and hemoglobin ß was decreased. However, cell proliferation was accelerated, apoptosis was inhibited, and the HSCs entered a cancerous state. The function of mitochondria was also abnormal, ROS production was decreased, and ATP concentration and ΔΨm were increased, which was related to the inhibition of apoptosis of stem cells. CONCLUSIONS: Taken together, we conclude that the high expression of BCL6 inhibits the differentiation and development of HSCs by affecting mitochondrial function, resulting in impaired growth and development of chickens. Moreover, the abnormal expression of BCL6 might be a cause of the clinical manifestations of chicken comb, pale skin, stunted growth and development, and the tendency to appear RSS in SLD chickens.

Cytokine inducible SH2-containing protein potentiate J subgroup avian leukosis virus replication and suppress antiviral responses in DF-1 chicken fibroblast cells.

Cytokine-inducible Srchomology2 (SH2)-containing protein (CIS) belongs to the suppressors of cytokine signaling (SOCS) protein family function as a negative feedback loop inhibiting cytokine signal transduction. J subgroup avian leukosis virus (ALV-J), a commonly-seen avian virus with a feature of immunosuppression, poses an unmeasurable threat to the poultry industry across the world. However, commercial medicines or vaccines are still no available for this virus. This study aims to evaluate the potential effect of chicken CIS in antiviral response and its role on ALV-J replication. The results showed that ALV-J strain SCAU-HN06 infection induced CIS expression in DF-1 cells, which was derived from chicken embryo free of endogenous avian sarcoma-leukosis virus (ASLV) like sequences. By overexpressing CIS, the expression of chicken type I interferon (IFN-I) and interferon-stimulated genes (ISGs; PKR, ZAP, CH25H, CCL4, IFIT5, and ISG12) were both suppressed. Meanwhile, data showed that CIS overexpression also increased viral yield. Interestingly, knockdown of CIS enhanced induction of IFN-I and ISGs and inhibited viral replication. Collectively, we proved that modulation of CIS expression not only affected SCAU-HN06 replication in vitro but also altered the expression of IFN-I and ISGs that act as an essential part of antiviral innate immune system. Our data provide a potential target for developing antiviral agents for ALV-J.

Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis.

Rationale: Invariant natural killer T (iNKT) cells and Kupffer cells represent major hepatic populations of innate immune cells. However, their roles in steatohepatitis remain poorly understood. To elucidate their functions in steatohepatitis development, real-time, in vivo analysis is necessary to understand the pathophysiological events in the dynamic interactions between them during diet-induced steatohepatitis. Methods: We used a steatohepatitis animal model induced by a methionine-choline-deficient (MCD) diet. Multi-photon confocal live imaging and conventional experimental techniques were employed to investigate the hepatic pathological microenvironment of iNKT and Kupffer cells, interactions between them, and the biological effects of these interactions in steatohepatitis. Results: We found that iNKT cells were recruited and aggregated into small clusters and interacted dynamically with Kupffer cells in the early stage of steatohepatitis. Most significantly, the iNKT cells in the cluster cleared free lipids released by necrotic hepatocytes and presented a non-classical activation state with high IFN-γ expression. Furthermore, the Kupffer cells in the cell cluster were polarized to type M1. The transcriptome sequencing of iNKT cells showed upregulation of genes related to phagocytosis and lipid processing. Adoptive transfer of iNKT cells to Jα18-/- mice showed that iNKT and Kupffer cell clusters were essential for balancing the liver and peripheral lipid levels and inhibiting liver fibrosis development. Conclusions: Our study identified an essential role for dynamic interactions between iNKT cells and Kupffer cells in promoting lipid phagocytosis and clearance by iNKT cells during early liver steatohepatitis. Therefore, modulating iNKT cells is a potential therapeutic strategy for early steatohepatitis.