A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development.

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

Preparation, biological activity and antibacterial properties of tantalum surface-doped Ca2+/Zn2+nanorods.

In this research, we utilize porous tantalum, known for its outstanding elastic modulus and biological properties, as a base material in biomedical applications. The human skeletal system is rich in elements like Ca and Zn. The role of Zn is crucial for achieving a spectrum of sterilizing effects, while Ca is known to effectively enhance cell differentiation and boost cellular activity. The focus of this study is the modification of porous tantalum using a hydrothermal method to synthesize Ca2+/Zn2+-doped Ta2O5nanorods. These nanorods are subjected to extensive characterization techniques to confirm their structure and composition. Additionally, their biological performance is evaluated through a range of tests, including antibacterial assessments, MTT assays, and bacteria/cell scanning electron microscopy (SEM) analyses. The objective is to determine the most effective method of surface modification for porous tantalum, thereby laying a foundational theoretical framework for its surface enhancement.

Bioactivity and antibacterial properties of zinc-doped Ta2O5nanorods on porous tantalum surface.

This paper focuses on the preparation of Zn2+-doped Ta2O5nanorods on porous tantalum using the hydrothermal method. Porous tantalum is widely used in biomedical materials due to its excellent elastic modulus and biological activity. Porous tantalum has an elastic modulus close to that of human bone, and its large specific surface area is conducive to promoting cell adhesion. Zinc is an important component of human bone, which not only has spectral bactericidal properties, but also has no cytotoxicity. The purpose of this study is to provide a theoretical basis for the surface modification of porous tantalum and to determine the best surface modification method. The surface structure of the sample was characterized by x-ray diffractometer, x-ray photoelectron spectroscopy, scanning electron microscope, transmission electron microscope, and the Zn-doped Ta2O5nanorods are characterized by antibacterial test, MTT test, ICP and other methods. The sample has good antibacterial properties and no cytotoxicity. The results of this study have potential implications for the development of new and improved biomedical materials.

Epstein-Barr Virus Envelope Glycoprotein gp110 Inhibits IKKi-Mediated Activation of NF-κB and Promotes the Degradation of ß-Catenin.

Epstein-Barr virus (EBV) infects host cells and establishes a latent infection that requires evasion of host innate immunity. A variety of EBV-encoded proteins that manipulate the innate immune system have been reported, but whether other EBV proteins participate in this process is unclear. EBV-encoded envelope glycoprotein gp110 is a late protein involved in virus entry into target cells and enhancement of infectivity. Here, we reported that gp110 inhibits RIG-I-like receptor pathway-mediated promoter activity of interferon-ß (IFN-ß) as well as the transcription of downstream antiviral genes to promote viral proliferation. Mechanistically, gp110 interacts with the inhibitor of NF-κB kinase (IKKi) and restrains its K63-linked polyubiquitination, leading to attenuation of IKKi-mediated activation of NF-κB and repression of the phosphorylation and nuclear translocation of p65. Additionally, gp110 interacts with an important regulator of the Wnt signaling pathway, ß-catenin, and induces its K48-linked polyubiquitination degradation via the proteasome system, resulting in the suppression of ß-catenin-mediated IFN-ß production. Taken together, these results suggest that gp110 is a negative regulator of antiviral immunity, revealing a novel mechanism of EBV immune evasion during lytic infection. IMPORTANCE Epstein-Barr virus (EBV) is a ubiquitous pathogen that infects almost all human beings, and the persistence of EBV in the host is largely due to immune escape mediated by its encoded products. Thus, elucidation of EBV's immune escape mechanisms will provide a new direction for the design of novel antiviral strategies and vaccine development. Here, we report that EBV-encoded gp110 serves as a novel viral immune evasion factor, which inhibits RIG-I-like receptor pathway-mediated interferon-ß (IFN-ß) production. Furthermore, we found that gp110 targeted two key proteins, inhibitor of NF-κB kinase (IKKi) and ß-catenin, which mediate antiviral activity and the production of IFN-ß. gp110 inhibited K63-linked polyubiquitination of IKKi and induced ß-catenin degradation via the proteasome, resulting in decreased IFN-ß production. In summary, our data provide new insights into the EBV-mediated immune evasion surveillance strategy.

Epstein-Barr virus envelope glycoprotein 110 inhibits NF-κB activation by interacting with NF-κB subunit p65.

Epstein-Barr virus (EBV) is a member of the lymphotropic virus family and is highly correlated with some human malignant tumors. It has been reported that envelope glycoprotein 110 (gp110) plays an essential role in viral fusion, DNA replication, and nucleocapsid assembly of EBV. However, it has not been established whether gp110 is involved in regulating the host's innate immunity. In this study, we found that gp110 inhibits tumor necrosis factor α-mediated NF- κB promoter activity and the downstream production of NF- κB-regulated cytokines under physiological conditions. Using dual-luciferase reporter assays, we showed that gp110 might impede the NF-κB promoter activation downstream of NF-κB transactivational subunit p65. Subsequently, we used coimmunoprecipitation assays to demonstrate that gp110 interacts with p65 during EBV lytic infection, and that the C-terminal cytoplasmic region of gp110 is the key interaction domain with p65. Furthermore, we determined that gp110 can bind to the N-terminal Rel homologous and C-terminal domains of p65. Alternatively, gp110 might not disturb the association of p65 with nontransactivational subunit p50, but we showed it restrains activational phosphorylation (at Ser536) and nuclear translocation of p65, which we also found to be executed by the C-terminal cytoplasmic region of gp110. Altogether, these data suggest that the surface protein gp110 may be a vital component for EBV to antagonize the host's innate immune response, which is also helpful for revealing the infectivity and pathogenesis of EBV.

Astragalus polysaccharide alleviated the inhibition of CSFV C-strain replication caused by PRRSV via the TLRs/NF­κB/TNF-α pathways.

It is a common phenomenon that PRRSV infection can interfere with the protective efficacy of the CSFV vaccine in clinical settings, and no effective treatment is available. In our previous study, we found that PRRSV infection could inhibit the replication of CSFV-C by promoting the high expression of inflammatory cytokines. In order to further investigate whether Chinese medicine could alleviate the inhibition effect, the PAM39 cells model, which was co-infected with PRRSV and CSFV-C, was established. The effects of Chinese medicine on this co-infection model, as well as the effect of astragalus polysaccharide on the TLRs/NF-κB/TNF-α pathways, were investigated. Our results demonstrated that PAM39 cells inoculated with different pathogenic PRRSV significantly inhibited the replication of CSFV-C and up-regulated the major inflammatory mediators, including TNF-α. For the following studies, 50 µM of astragalus polysaccharide was selected from six kinds of representative Chinese medicine based on their cytotoxicity, viral titers, and inflammatory mediators. Further experiments indicated that astragalus polysaccharide could alleviate the inhibition of CSFV-C replication in the co-infection group with no influence on cell viability. In addition, astragalus polysaccharide treatment clearly reduced P65 phosphorylation and down-regulated the expression of TLR7, TLR9, and TNF-α in co-infection group, implying that the TLRs/NF-κB/TNF-α pathways may play an important role in astragalus polysaccharide's anti-inflammatory response. In conclusion, astragalus polysaccharide treatment alleviated PRRSV-mediated inhibition of CSFV-C replication via the TLRs/NF-κB/TNF-α pathways, and the molecular mechanism of PRRSV co-infection leading to the failure of CSFV vaccine immunization was partially elucidated, providing a scientific basis for effective CSF prevention and control in pig farms.

Proteomic Analysis of Vero Cells Infected with Pseudorabies Virus.

Suid herpesvirus 1 (SuHV-1), known as pseudorabies virus (PRV), is one of the most devastating swine pathogens in China, particularly the sudden occurrence of PRV variants in 2011. The higher pathogenicity and cross-species transmission potential of the newly emerged variants caused not only colossal economic losses, but also threatened public health. To uncover the underlying pathogenesis of PRV variants, Tandem Mass Tag (TMT)-based proteomic analysis was performed to quantitatively screen the differentially expressed cellular proteins in PRV-infected Vero cells. A total of 7072 proteins were identified and 960 proteins were significantly regulated: specifically 89 upregulated and 871 downregulated. To make it more credible, the expression of XRCC5 and XRCC6 was verified by western blot and RT-qPCR, and the results dovetailed with the proteomic data. The differentially expressed proteins were involved in various biological processes and signaling pathways, such as chaperonin-containing T-complex, NIK/NF-κB signaling pathway, DNA damage response, and negative regulation of G2/M transition of mitotic cell cycle. Taken together, our data holistically outline the interactions between PRV and host cells, and our results may shed light on the pathogenesis of PRV variants and provide clues for pseudorabies prevention.

Protective effect of Asarum sieboldii essential oil on ovalbumin induced allergic rhinitis in rat.

BACKGROUND: The study was aimed to investigate the protective effect of Asarum sieboldii Miq. essential oil (AEO) on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats. METHODS AND RESULTS: Sixty Sprague-Dawley male rats were randomly divided into six groups (n=10): control, model, cetirizine (Cet, 4.65 g/kg), and AEO (0.5, 1.5, 3 g/kg) groups. All animals except the control group received repeated intranasal instillation with 20 µl of 20% OVA in Al(OH)3 saline solvent for 15 days. The control group was intranasally instilled with 5 mg/ml of Al(OH)3 instead of the same procedure. In the 15 days, Cet and AEO were orally administrated for 28 days. At the end of the drug administration, 20 µl of 5% OVA was given to animals to stimulate allergic reaction, then the rat behavioral detection, assessment of the patho-morphological changes in nasal mucosa, and the serum biomarkers were determined. The result showed that AEO could significantly reduce the amount of nasal secretions, sneezing, and the degree of nasal scratching in AR rats with EC50 = 1.5 and 2.8 g/kg, respectively. The degree of nasal mucosal inflammation in AEO group improved, the levels of immunoglobulin E (IgE), histamine, IL-4, IL-5, IL-17 were decreased, and the level of IFN-γ was increased obviously with EC50 = 2 g/kg. CONCLUSION: The study suggested that the possible mechanism might be related with the inhibition of histamine release and regulation of the cytokine levels, which plays an important role in the treatment of AR.

Allergic Rhinitis in Rats Is Associated with an Inflammatory Response of the Hippocampus.

Allergic rhinitis (AR) is a major concern in personal and public health, which negatively affects emotions and behavior, leading to cognitive deficits, memory decline, poor school performance, anxiety, and depression. Several cellular and molecular mediators are released in the inflammatory process of AR and activate common neuroimmune mechanisms, involving emotionally relevant circuits and the induction of anxiety. Responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to allergic processes have been reported, which may also include responsiveness of the hippocampus, cortex, and other brain regions. Here, we have used an optimized rat model of AR to explore whether the disease has a relationship with inflammatory responses in the hippocampus. AR was established in adult rats by ovalbumin sensitization, and the expression of various inflammatory substances in the hippocampus was measured by specific assays. Comparison between experimental and various control groups of animals revealed an association of AR with significant upregulation of substance P, microglia surface antigen (CD11b), glial fibrillary acid protein (GFAP), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) in the hippocampus. Thus, we hypothesize that the AR challenge may activate these inflammatory mediators in the hippocampus, which in turn contribute to the abnormal behavior and neurological deficits associated with AR.