miR-155 facilitates the synergistic replication between avian leukosis virus subgroup J and reticuloendotheliosis virus by targeting a dual pathway.

IMPORTANCE: The synergy of two oncogenic retroviruses is an essential phenomenon in nature. The synergistic replication of ALV-J and REV in poultry flocks increases immunosuppression and pathogenicity, extends the tumor spectrum, and accelerates viral evolution, causing substantial economic losses to the poultry industry. However, the mechanism of synergistic replication between ALV-J and REV is still incompletely elusive. We observed that microRNA-155 targets a dual pathway, PRKCI-MAPK8 and TIMP3-MMP2, interacting with the U3 region of ALV-J and REV, enabling synergistic replication. This work gives us new targets to modulate ALV-J and REV's synergistic replication, guiding future research on the mechanism.

Tunable nonreciprocal metasurfaces based on a nonlinear quasi-bound state in the continuum.

Nonreciprocal devices are essential and crucial in optics for source protection and signal separation. A hybrid grating system consisting of a silicon grating, a graphene layer, and a silicon waveguide layer is employed to create a high-Q quasi-BIC (bound state in the continuum). Then, the high-Q properties of the quasi-BIC are harnessed to enhance the third-order nonlinear effect of silicon, thereby improving the nonreciprocal characteristics of the device. The nonreciprocal transmittance ratio of the device can be tunable by adjusting the graphene Fermi energy level, achieving tunability ranging from 0.0865 to 30.57 dB. It also enables the best performance of the device over a wider range of frequency bands. This study provides a new, to the best of our knowledge, method for designing tunable nonreciprocal devices with a wide range of potential applications.

The CCCH-Type Zinc Finger Antiviral Protein Relieves Immunosuppression of T Cells Induced by Avian Leukosis Virus Subgroup J via the NLP-PKC-δ-NFAT Pathway.

The CCCH-type zinc finger antiviral protein (ZAP) can recognize and induce the degradation of mRNAs and proteins of certain viruses, as well as exerting its antiviral activity by activating T cells. However, the mechanism of ZAP that mediates T cell activation during virus infection remains unclear. Here, we found a potential function of ZAP that relieves immunosuppression of T cell induced by avian leukosis virus subgroup J (ALV-J) via a novel signaling pathway that involves norbin-like protein (NLP), protein kinase C delta (PKC-δ), and nuclear factor of activated T cell (NFAT). Specifically, ZAP expression activated T cells by promoting the dephosphorylation and nuclear translocation of NFAT. Furthermore, knockdown of ZAP weakened the reactivity and antiviral response of T cells. Mechanistically, ZAP reduced PKC-δ activity by upregulating and reactivating NLP by competitively binding with viral protein. Knockdown of NLP decreased the dephosphorylation of PKC-δ by ZAP expression. Moreover, we show that knockdown of PKC-δ reduced the phosphorylation levels of NFAT and enhanced its nuclear translocation. Taken together, these data revealed that ZAP relieves immunosuppression caused by ALV-J and mediates T cell activation through the NLP-PKC-δ-NFAT pathway. IMPORTANCE The evolution of the host defense system is driven synchronously in the process of resisting virus invasion. Accordingly, host innate defense factors effectively work to suppress virus replication. However, it remains unclear whether the host innate defense factors are involved in antiviral immune responses against the invasion of immunosuppressive viruses. Here, we found that CCCH-type zinc finger antiviral protein (ZAP) effectively worked in resistance to immunosuppression caused by avian leukosis virus subgroup J (ALV-J), a classic immunosuppressive virus. Evidence showed that ZAP released the phosphatase activity of NLP inhibited by ALV-J and further activated NFAT by inactivating PKC-δ. This novel molecular mechanism, i.e., ZAP regulation of the antiviral immune response by mediating the NLP-PKC-δ-NFAT pathway, has greatly enriched the understanding of the functions of host innate defense factors and provided important scientific ideas and a theoretical basis for research on immunosuppressive viruses and antiviral immunity.

Interaction between Avian Leukosis Virus Subgroup J Surface Protein and Doublecortin-Like Kinase 1 Accelerates Cell Proliferation and Epithelial-Mesenchymal Transition.

Avian leukosis virus subgroup J (ALV-J) induces myelocytomas, which can metastasize to multiple organs in diseased chickens. Although metastasis is the primary cause of death in such cases, the mechanism for it remains unclear. Here, we found that interaction between ALV-J surface protein (SU) and doublecortin-like kinase 1 (DCLK1) promotes epithelial-mesenchymal transition (EMT) and cell proliferation. We found that ALV-J can activate EMT in infected cells. Subsequently, proteomics analysis revealed that DCLK1, a well-established putative tumor stem cell marker, which is highly expressed in ALV-J-infected DF-1 cells and chickens, might be a potential factor mediating EMT. Furthermore, using immunofluorescence and immunoprecipitation, we verified that SU interacts with DCLK1. Functional studies suggested that overexpression of DCLK1 increased viral replication and promoted cell proliferation by accelerating the progression of cells from the G0/G1 phase to the S phase of cell cycle, whereas RNA interference of DCLK1 reduced viral replication and arrested cell proliferation by retarding cell cycle progression from the late G1 phase into the S phase in ALV-J-infected cells. Moreover, we demonstrate that the increased accumulation of DCLK1 promotes EMT by increasing the expression of N-cadherin, vimentin, MMP2, and transcription factor Snail1 and decreasing the expression of epithelial marker E-cadherin. These results suggest that ALV-J SU interacts with DCLK1, and accelerates cell proliferation, leading to increased viral replication and ultimately activating EMT, which paves the way for tumor metastasis. IMPORTANCE Tumor metastasis is a major challenge in cancer research, because of its systemic nature and the resistance of disseminated tumor cells to existing therapeutic agents. It is estimated that >90% of mortality from cancer is attributable to metastases. We found that ALV-J can activate EMT, which plays a critical role in cancer metastasis. Subsequently, we identified a tumor stem cell marker, DCLK1, in ALV-J infected cells, which interacts with surface protein (SU) of ALV-J to promote virus replication, activate EMT, and accelerate cell proliferation enabling ALV-J to obtain metastatic ability. Understanding the process of participation of ALV-J in EMT and the route of metastasis will help elucidate the mechanism of virus-induced tumor metastasis and help identify promising molecular targets and key obstacles for ALV-J control and clinical technology development.

Modeling the XBB strain of SARS-CoV-2: Competition between variants and impact of reinfection.

XBB, an Omicron subvariant of SARS-CoV-2 that began to circulate in late 2022, has been dominant in the US since early 2023. To quantify the impact of XBB on the progression of COVID-19, we propose a new mathematical model which describes the interplay between XBB and other SARS-CoV-2 variants at the population level and which incorporates the effects of reinfection. We apply the model to COVID-19 data in the US that include surveillance data on the cases and variant proportions from the New York City, the State of New York, and the State of Washington. Our fitting and simulation results show that the transmission rate of XBB is significantly higher than that of other variants and the reinfection from XBB may play an important role in shaping the pandemic/epidemic pattern in the US.

Molecular characteristics and pathogenicity of a novel chicken astrovirus variant.

It is well-established that the genetic diversity, regional prevalence, and broad host range of astroviruses significantly impact the poultry industry. In July 2022, a small-scale commercial broiler farm in China reported cases of growth retardation and a 3% mortality rate. From chickens displaying proventriculitis and pancreatitis, three chicken astroviruses (CAstV) isolates were obtained and named SDAU2022-1-3. Complete genomic sequencing and analysis revealed the unique characteristics of these isolates from known CAstV strains in ORF1a, ORF1b, and ORF2 genes, characterized by an unusually high variability. Analysis of amino acid mutations in ORF1a, ORF1b, and ORF2 indicated that the accumulation of these mutations played a pivotal role in the emergence of the variant strain. Inoculation experiments demonstrated that affected chickens exhibited liver and kidney enlargement, localized proventricular hemorrhage, and a dark reddish-brown appearance in about two-thirds of the pancreas. Histopathological examination unveiled hepatic lymphocytic infiltration, renal tubular epithelial cell swelling, along with lymphocytic proventriculitis and pancreatitis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis indicated viremia and viral shedding at 3 days post-infection (dpi). The proventriculus displayed the highest viral loads, followed by the liver, kidney, duodenum, and pancreas. Liver parameters (AST and ALT) and kidney parameters (UA and UN) demonstrated mild damage consistent with earlier findings. While the possibility of new mutations in the ORF2 gene of CAstV causing proventriculitis and pancreatitis warrants further investigation, these findings deepen our comprehension of CAstV's pathogenicity in chickens. Additionally, they serve as valuable references for subsequent research endeavors.

Biodegradable FePS3 nanoplatform for efficient treatment of osteosarcoma by combination of gene and NIR-II photothermal therapy.

As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.

Fabricating Black-Phosphorus/Iron-Tetraphosphide Heterostructure via a Solid-Phase Solution-Precipitation Method for High-Performance Nitrogen Reduction.

Although constructing heterostructures is considered as one of the most successful strategies to improve the activity of a catalyst, the heterostructures usually suffer from the cumbersome preparation treatments and low-yield. Inspired by a solid-phase solution-precipitation (SPSP) process, an approach for interface intensive heterostructures with high yield is developed. Herein, a black-phosphorus/iron-tetraphosphide (BP/FeP4 ) heterostructure is prepared mechanochemically with high transient pressure by the solid-phase ball milling approach. The BP/FeP4 heterostructure delivers excellent catalytic performance in the nitrogen reduction reaction (NRR) as exemplified by an NH3 yield of 77.6 µg h-1 mg cat . - 1 \[{\rm{mg}}_{{\rm{cat}}{\rm{.}}}^{{\bm{ - }}1}\] and Faradic efficiency of 62.9% (-0.2 V), which are superior to that of most NRR catalysts recently reported. Experimental investigation and density-functional theory calculation indicate the importance of excess phosphorus in the heterostructures on the NRR activity, which assists the Fe atom to activate N2 via adsorbing the H atom. The results demonstrate the great potential of this new type of heterostructures prepared by the SPSP approach. Benefiting from the simple preparation process and low cost, the heterostructures offer a new insight into the development of highly efficient catalysts.

Carbon Nitride with Rationally Designed π-Conjugated Structure for Bright Blue-Violet Light-Emitting Diodes.

Carbon nitride consisting of the broken π-conjugated structure (bc-CN) is designed as the emitting layer in a blue-violet light emitting diode (LED). The bc-CN is prepared by a metal-oxide (MgO) template-assisted method, in which the low reaction temperature and nano MgO jointly control the degree of polymerization to form cyano groups and broken π-conjugation in the bc-CN nanosheets (bc-CN NS) which emit intense blue-violet photoluminescence at 412 nm. The broken π-conjugated heptazine-ring structure in the bc-CN NS mitigates non-radiation energy loss and promotes the d*-LP transition. As a result, a high quantum efficiency of 73.1% is achieved. The excellent dispersing ability of the bc-CN NS enables solution-based fabrication of the light emitting diode (LED). The LED exhibits intense electroluminescence of 236 cd m-2 at 412 nm with an external quantum efficiency of 0.46%. The broken π-conjugation modulates the optical properties of the polymerized carbon nitride semiconductor giving rise to intense blue-violet electroluminescence, which is very desirable for printable and wide-color-gamut display devices.

TMT-based proteomic analysis reveals integrins involved in the synergistic infection of reticuloendotheliosis virus and avian leukosis virus subgroup J.

BACKGROUND: Co-infection with the avian leukosis virus subgroup J (ALV-J) and the reticuloendotheliosis virus (REV) increases mutual viral replication, causing a more serious pathogenic effect by accelerating the progression of neoplasia and extending the tumor spectrum. However, the molecular mechanism underlying the synergistic replication of ALV-J and REV remains unclear. RESULTS: Here, we performed this study to compare the differentially expressed proteins among CEF cells infected with ALV-J, REV or both at the optimal synergistic infection time using TMT-based quantitative proteomics. We identified a total of 719 (292 upregulated and 427 downregulated) and 64 (35 upregulated and 29 downregulated) proteins by comparing co-infecting both viruses with monoinfecting ALV-J and REV, respectively. GO annotation and KEGG pathway analysis showed the differentially expressed proteins participated in virus-vector interaction, biological adhesion and immune response pathways in the synergistic actions of ALV-J and REV at the protein levels. Among the differentially expressed proteins, a large number of integrins were inhibited or increased in the co-infection group. Further, eight integrins, including ITGα1, ITGα3, ITGα5, ITGα6, ITGα8, ITGα9, ITGα11 and ITGß3, were validated in CEF cells by qRT-PCR or western blot. CONCLUSIONS: These findings proved that integrins may be key regulators in the mechanism of synergistic infection of REV and ALV-J, which will provide more insight into the pathogenesis of synergism of REV and ALV-J at protein level.

Long read sequencing revealed proventricular virome of broiler chicken with transmission viral proventriculitis.

BACKGROUND: Transmissible viral proventriculitis (TVP) causes significant economic loss to the poultry industry. However, the exact causative agents are obscure. Here we examine the virome of proventriculus from specified pathogen free (SPF) chickens that reproduced by infection of proventricular homogenate from broiler chicken with TVP using long read sequencing of the Pacific Biosciences RSII platform. The normal SPF chickens were used as control. RESULTS: Our investigation reveals a virome of proventriculitis, including three Gyrovirus genera of the Aneloviridae: Gyrovirus homsa1 (GyH1) (also known as Gyrovirus 3, GyV3) (n = 2662), chicken anemia virus (CAV) (n = 482) and Gyrovirus galga1 (GyG1) (also known as avian Gyrovirus 2, AGV2) (n = 11); a plethora of novel CRESS viral genomes (n = 26) and a novel genomovirus. The 27 novel viruses were divided into three clusters. Phylogenetic analysis showed that the GyH1 strain was more closely related to the strains from chicken (MG366592) than mammalian (human and cat), the GyG1 strain was closely related to the strains from cat in China (MK089245) and from chicken in Brazil (HM590588), and the CAV strain was more closely related to the strains from Germany (AJ297684) and United Kingdom (U66304) than that previously found in China. CONCLUSION: In this study, we revealed that Gyrovirus virome showed high abundance in chickens with TVP, suggesting their potential role in TVP, especially GyH1. This study is expected to contribute to the knowledge of the etiology of TVP.

Serological investigation of Gyrovirus homsa1 infections in chickens in China.

BACKGROUND: Gyrovirus homsa1 (GyH1) (also known as Gyrovirus 3, GyV3) is a non-enveloped, small, single-stranded DNA virus, which was first identified in children with acute diarrhea, and was subsequently detected in marketed chickens, broilers with transmissible viral proventriculitis (TVP), and mammals. GyH1 is a pathogenic virus in chickens, causing aplastic anemia, immunosuppression, and multisystem damage. However, the seroepidemiology of GyH1 infection in chickens remains unclear. Here, we investigated the seroprevalence of GyH1 in chickens by ELISA to reveal the endemic status of GyH1 in China. RESULTS: An indirect ELISA with high sensitivity and specificity was developed for investigation of seroepidemiology of GyH1 in chickens in China. The seropositive rate of GyH1 ranged from 0.6% to 7.7% in thirteen provinces, and ranged from 4.1% to 8.1% in eight species chickens. The seropositive rate of GyH1 in broiler breeders was significantly higher than that of in layers. There was a negative correlation between seropositive rate and age of chickens. The highest and lowest seropositive rate were present in chickens at 30-60 days and over 180 days, respectively. CONCLUSIONS: The seroepidemiological investigation results demonstrated that natural GyH1 infection is widespread in chickens in China. Different species showed different susceptibility for GyH1. Aged chickens showed obvious age-resistance to GyH1. GyH1 has shown a high risk to the poultry industry and should be highly concerned.

High-frequency and activation of CD4+CD25+ T cells maintain persistent immunotolerance induced by congenital ALV-J infection.

Congenital avian leukosis virus subgroup J (ALV-J) infection can induce persistent immunotolerance in chicken, however, the underlying mechanism remains unclear. Here, we demonstrate that congenital ALV-J infection induces the production of high-frequency and activated CD4+CD25+ Tregs that maintain persistent immunotolerance. A model of congenital infection by ALV-J was established in fertilized eggs, and hatched chicks showed persistent immunotolerance characterized by persistent viremia, immune organ dysplasia, severe imbalance of the ratio of CD4+/CD8+ T cells in blood and immune organs, and significant decrease in CD3+ T cells and Bu-1+ B cells in the spleen. Concurrently, the mRNA levels of IL-2, IL-10, and IFN-γ showed significant fluctuations in immune organs. Moreover, the frequency of CD4+CD25+ Tregs in blood and immune organs significantly increased, and the frequency of CD4+CD25+ Tregs was positively correlated with changes in ALV-J load in immune organs. Interestingly, CD4+CD25+ Tregs increased in the marginal zone of splenic nodules in ALV-J-infected chickens and dispersed to the germinal center. In addition, the proliferation and activation of B cells in splenic nodules was inhibited, and the number of IgM+ and IgG+ cells in the marginal zone significantly decreased. We further found that the mRNA levels of TGF- ß and CTLA-4 in CD4+CD25+ Tregs of ALV-J-infected chickens significantly increased. Together, high-frequency and activated CD4+CD25+ Tregs inhibited B cells functions by expressing the inhibitory cytokine TGF-ß and inhibitory surface receptor CTLA-4, thereby maintaining persistent immunotolerance in congenital ALV-J-infected chickens.

Kinetic analysis of pathogenicity and tissue tropism of gyrovirus 3 in experimentally infected chickens.

Gyrovirus 3 (GyV3), the third novel emerging species of the genus Gyrovirus of the Anelloviridae family, has been described in multiple hosts. Epidemiologically, there are suggestions that GyV3 is associated with diarrhea/proventriculitis, however, no direct causal evidence exists between GyV3 infection and specific clinical diseases. Herein, we infected special pathogen-free (SPF) chickens with GyV3, and then assessed the pathogenicity and tissue tropism. The results revealed that GyV3 induced persistent infection characterized by diarrhea, aplastic anemia, immunosuppression, and persistent systemic lymphocytic inflammation. Clinically, the infected chickens presented ruffled feathers, diarrhea, anemia, and weight loss. Aplastic anemia was characterized by progressive depletion of hematopoietic cells in the bone marrow, immunosuppression was associated with atrophy of the thymus, spleen, and bursa of Fabricious, progressive lymphocytic inflammations were characterized by proventriculitis, adrenalitis, pancreatitis, hepatitis, nephritis, and bronchitis. Viral loads of GyV3 in tissues exhibited "M", "N", "W" or "V" type dynamic changes. The highest level of viral loads was reported in bone marrow at 7dpi, followed by the adrenal gland at 2 dpi, the sciatic nerve at 7 dpi, and bile at 35 dpi. The bone marrow and kidney demonstrate the strongest immunostaining of GyV3-VP1 antigen and were suggested as the target tissues of GyV3. Collectively, GyV3 is an immunosuppressive pathogenic virus that targets the bone marrow and kidney in chickens. Exploring the pathogenicity and tissue tropism of GyV3 will guide the basic understanding of the biology of GyV3 and its pathogenesis in chickens.

From Octahedron Crystals to 2D Silicon Nanosheets: Facet-Selective Cleavage and Biophotonic Applications.

2D silicon nanosheets (SiNSs) are promising materials for biomedicine but facile synthesis of SiNSs remains a challenge. Herein, by means of a sulfur-iodine co-assisted chemical vapor transport method, octahedron silicon (oct-Si) crystals with fully exposed {111} planes are prepared as precursors for efficient synthesis of SiNSs by facet-selective exfoliation. The 13 nm thick SiNSs have good biocompatibility and the sharp Raman scattering signal facilitates intracellular Raman imaging upon exposure to a near-infrared (NIR) laser. Furthermore, the SiNSs have excellent NIR photothermal characteristics such as a large extinction coefficient of 11.3 L g-1 cm-1 and high photothermal conversion efficiency of 21.4% at 1064 nm. In vitro experiments demonstrate superior NIR-II photothermal therapeutic effects in killing cancer cells. Comparing to conventional methods, the novel facet-selective cleavage strategy is more controllable and environmentally friendly boding well for the fabrication of non-van der Waals 2D materials. The multimodal photonic behavior also suggests large potential of the SiNSs pertaining to integrated multi-NIR biophotonic techniques using single nanomaterials.

Complete optical absorption in hybrid halide perovskites based on critical coupling in the communication band.

In order to remarkably enhance the absorption capability of (CH3NH3)PbI3, a tunable narrow-band (CH3NH3)PbI3-based perfect absorber based on the critical coupling with guided resonance is proposed. By using the finite-difference time-domain (FDTD) simulations, a complete absorption peak is achieved at the wavelength of 1310 nm. Moreover, we have compared the simulation results with theoretical calculations, which agree well with each other. By changing related structural parameters, the wavelength of absorption peak can be tuned effectively. Furthermore, the proposed absorber can tolerate a relatively wide range of incident angles and demonstrate polarization-independence. In addition to (CH3NH3)PbI3, the complete optical absorption in the other halide perovskites can be realized by the same mechanism.

Regulatory effects of chicken TRIM25 on the replication of ALV-A and the MDA5-mediated type I interferon response.

This study focuses on the immunoregulatory effects of chicken TRIM25 on the replication of subgroup A of avian leukosis virus (ALV-A) and the MDA5-mediated type I interferon response. The ALV-A-SDAU09C1 strain was inoculated into DF1 cells and 1-day-old SPF chickens, and the expression of TRIM25 was detected at different time points after inoculation. A recombinant overexpression plasmid containing the chicken TRIM25 gene (TRIM25-GFP) was constructed and transfected into DF1 cells to analyse the effects of the overexpression of chicken TRIM25 on the replication of ALV-A and the expression of MDA5, MAVS and IFN-ß. A small interfering RNA targeting chicken TRIM25 (TRIM25-siRNA) was prepared and transfected into DF1 cells to assess the effects of the knockdown of chicken TRIM25 on the replication of ALV-A and the expression of MDA5, MAVS and IFN-ß. The results showed that chicken TRIM25 was significantly upregulated at all time points both in ALV-A-infected cells and in ALV-A-infected chickens. Overexpression of chicken TRIM25 in DF1 cells dramatically decreased the antigenic titres of ALV-A in the cell supernatant and upregulated the relative expression of MDA5, MAVS and IFN-ß induced by ALV-A or by poly(I:C); in contrast, knockdown of chicken TRIM25 significantly increased the antigenic titres of ALV-A and downregulated the relative expression of MDA5, MAVS and IFN-ß. It can be concluded that chicken TRIM25 can inhibit the replication of ALV-A and upregulate the MDA5 receptor-mediated type I interferon response in chickens. This study can help improve the understanding of the antiviral activities of chicken TRIM25 and enrich the knowledge of antiviral responses in chickens.

Crystalline Red Phosphorus Nanoribbons: Large-Scale Synthesis and Electrochemical Nitrogen Fixation.

Two dimensional (2D) nanoribbons constitute an emerging nanoarchitecture for advanced microelectronics and energy conversion due to the stronger size confinement effects compared to traditional nanosheets. Triclinic crystalline red phosphorus (cRP) composed by a layered structure is a promising 2D phosphorus allotrope and the tube-like substructure is beneficial to the construction of nanoribbons. In this work, few-layer cRP nanoribbons are synthesized and the effectiveness in the electrochemical nitrogen reduction reaction (NRR) is investigated. An iodine-assisted chemical vapor transport (CVT) method is developed to synthesize circa 10 g of bulk cRP lumps with a yield of over 99 %. With the aid of probe ultrasonic treatment, high-quality cRP microcrystals are exfoliated into few-layer nanoribbons (cRP NRs) with large aspect ratios. As non-metallic materials, cRP NRs are suitable for the electrochemical nitrogen reduction reaction. The ammonia yield is 15.4 µg h-1 mgcat. -1 at -0.4 V vs. reversible hydrogen electrode in a neutral electrolyte under ambient conditions and the Faradaic efficiency is 9.4 % at -0.2 V. Not only is cRP a promising catalyst, but also the novel strategy expands the application of phosphorus-based 2D structures beyond that of traditional nanosheets.

Clonal anergy of CD117+chB6+ B cell progenitors induced by avian leukosis virus subgroup J is associated with immunological tolerance.

BACKGROUND: The pathogenesis of immunological tolerance caused by avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, is largely unknown. RESULTS: In this study, the development, differentiation, and immunological capability of B cells and their progenitors infected with ALV-J were studied both morphologically and functionally by using a model of ALV-J congenital infection. Compared with posthatch infection, congenital infection of ALV-J resulted in severe immunological tolerance, which was identified as the absence of detectable specific antivirus antibodies. In congenitally infected chickens, immune organs, particularly the bursa of Fabricius, were poorly developed. Moreover, IgM-and IgG-positive cells and total immunoglobulin levels were significantly decreased in these chickens. Large numbers of bursa follicles with no differentiation into cortex and medulla indicated that B cell development was arrested at the early stage. Flow cytometry analysis further confirmed that ALV-J blocked the differentiation of CD117+chB6+ B cell progenitors in the bursa of Fabricius. Furthermore, both the humoral immunity and the immunological capability of B cells and their progenitors were significantly suppressed, as assessed by (a) the antibody titres against sheep red blood cells and the Marek's disease virus attenuated serotype 1 vaccine; (b) the proliferative response of B cells against thymus-independent antigen lipopolysaccharide (LPS) in the spleen germinal centres; and (c) the capacities for proliferation, differentiation and immunoglobulin gene class-switch recombination of B cell progenitors in response to LPS and interleukin-4(IL-4) in vitro. CONCLUSIONS: These findings suggested that the anergy of B cells in congenitally infected chickens is caused by the developmental arrest and dysfunction of B cell progenitors, which is an important factor for the immunological tolerance induced by ALV-J.

Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs.

BACKGROUND: Co-infection with avian leukosis virus subgroup J and reticuloendotheliosis virus induces synergistic pathogenic effects and increases mortality. However, the role of exosomal miRNAs in the molecular mechanism of the synergistic infection of the two viruses remains unknown. RESULTS: In this study, exosomal RNAs from CEF cells infected with ALV-J, REV or both at the optimal synergistic infection time were analysed by Illumina RNA deep sequencing. A total of 54 (23 upregulated and 31 downregulated) and 16 (7 upregulated and 9 downregulated) miRNAs were identified by comparing co-infection with two viruses, single-infected ALV-J and REV, respectively. Moreover, five key miRNAs, including miR-184-3p, miR-146a-3p, miR-146a-5p, miR-3538 and miR-155, were validated in both exosomes and CEF cells by qRT-PCR. GO annotation and KEGG pathway analysis of the miRNA target genes showed that the five differentially expressed miRNAs participated in virus-vector interaction, oxidative phosphorylation, energy metabolism and cell growth. CONCLUSIONS: We demonstrated that REV and ALV-J synergistically increased the accumulation of exosomal miRNAs, which sheds light on the synergistic molecular mechanism of ALV-J and REV.