REC8 meiotic recombination protein (REC8) is a member of structural maintenance of chromosome (SMC) protein partners, which play an important role in meiosis, anti-tumor, and sperm formation. As the adapter proteins of RLR signaling and cGAS-DNA signaling, the activity and stability of MAVS (also known as VISA, Cardif and IPS-1) and STING (also known as MITA) are critical for innate immunity. Here, we report that REC8 interacts with MAVS and STING, and inhibits their ubiquitination and subsequent degradation, thereby promoting innate antiviral signaling. REC8 is upregulated through the JAK-STAT signaling pathway under viral infection. Knockdown of REC8 impair the innate immune responses against VSV (Vesicular Stomatitis Virus), NDV (Newcastle disease virus) and HSV (herpes simplex virus). Mechanistically, under the infection of viruses, the SUMOylated REC8 is transferred from the nucleus to the cytoplasm and then interacts with MAVS and STING to inhibit their K48-linked ubiquitination triggered by RNF5. Moreover, REC8 promotes the recruitment of TBK1 to MAVS and STING. Thus, REC8 functions as a positive modulator of innate immunity. Our work highlights a previously undocumented role of meiosis-associated protein REC8 in regulating innate immunity.
IMPORTANCE
The innate immune response is crucial for the host to resist the invasion of viruses and other pathogens. STING and MAVS play a critical role in the innate immune response to DNA and RNA viral infection, respectively. In this study, REC8 promotes the innate immune response by targeting STING and MAVS. Notably, REC8 interacts with MAVS and STING in the cytoplasm and inhibits K48-linked ubiquitination of MAVS and STING triggered by RNF5, stabilizing MAVS and STING protein to promote innate immunity and gradually inhibiting viral infection. Our study provides a new insight for the study of antiviral innate immune.
Callicarpa kwangtungenis (C. Kw), C. macroph ylla (C. Ma), C. nudiflora (C. Nu), C. formosana (C. Fo), and C. kochiana (C. Ko) were medicinal plant resource in China. The aim of this study is to fully identify the chemical components, explore the similarities and differences, as well as evaluate the anti-hyperuricemia effects of these five Callicarpa leaves extracts. The UPLC/Q-TOF-MS analysis was performed and 151 compounds were identified. PCA suggested that there exist large metabolite differences between these five callicarpa species extracts. Meanwhile, metabolic profiles of C. Nu, C. Ko and C. Kw leaves differ significantly from the other two callicarpa species, while C. Fo and C. Ma share similar chemical constituents. OPLS-DA highlight with an S-plot indicated that there are 14 robust known chemical markers enabling the differentiation between these five Callicarpa plants. What is more, C. Ma, C. Nu, and C. Fo leaves extracts treatment effectively reversed the body weight loss, uric acid and creatinine content, hepatic XOD activity, kidney, liver, and ankle tissues injury and inflammation induced by potassium oxonate in hyperuricemia mice. While Ko and C. Kw leaves extracts treatment showed less improvement in hyperuricemia mice. This study supplied new therapeutic medicines for treating hyperuricemia, provided a new direction for exploitation of Callicarpa plants resources.
The effective removal of oxytetracycline hydrochloride (OTC) from the water environment is of great importance. Adsorption as a simple, stable, and cost-effective technology is regarded as an important method for removing OTC. Herein, a low-cost biochar with a developed mesoporous structure was synthesized via pyrolysis of poplar leaf with potassium bicarbonate (KHCO3) as the activator. KHCO3 can endow biochar with abundant mesopores, but excessive KHCO3 cannot continuously promote the formation of mesoporous structures. In comparison with all of the prepared biochars, PKC-4 (biochar with a poplar leaf to KHCO3 mass ratio of 5:4) shows the highest adsorption performance for OTC as it has the largest surface area and richest mesoporous structure. The pseudo-second-order kinetic model and the Freundlich equilibrium model are more consistent with the experimental data, which implies that the adsorption process is multi-mechanism and multi-layered. In addition, the maximum adsorption capacities of biochar are slightly affected by pH changes, different metal ions, and different water matrices. Moreover, the biochar can be regenerated by pyrolysis, and its adsorption capacity only decreases by approximately 6% after four cycles. The adsorption of biochar for OTC is mainly controlled by pore filling, though electrostatic interactions, hydrogen bonding, and π-π interaction are also involved. This study realizes biomass waste recycling and highlights the potential of poplar leaf-based biochar for the adsorption of antibiotics.
Context
Current chemotherapeutic drugs cannot meet the treatment needs of patients with nasopharyngeal carcinoma (NPC), so urgent action is needed to discover novel chemotherapeutic agents. Our previous study revealed that garcinone E (GE) inhibited the proliferation and metastasis of NPC, suggesting that the compound might display promising anticancer activity.
Objective
To examine the mechanism underlying the anti-NPC activity of GE for the first time.
Materials and methods
For MTS assay, NPC cells were treated with 2.5-20 μmol/L GE or dimethyl sulfoxide for 24, 48, and 72 h. Colony formation capacity, cell cycle distribution, and
in vivo
xenograft experiment of GE were assessed. MDC staining, StubRFP-sensGFP-LC3 observation, LysoBrite Blue staining, and immunofluorescence examined the autophagy of NPC cells after GE exposure. Western blotting, RNA-sequencing, and RT-qPCR measured protein and mRNA levels.
Results
GE suppressed cell viability with an IC
50
of 7.64, 8.83 and 4.65 μmol/L for HK1, HONE1 and S18 cells. GE inhibited colony formation and cell cycle, increased autophagosome number, and inhibited the autophagic flux partially by blocking lysosome-autophagosome fusion, and repressed S18 xenograft growth. GE dysregulated the expression of autophagy- and cell cycle-related proteins such as Beclin-1, SQSTM1/p62, LC3, CDKs, and Cyclins. Bioinformatics GO and KEGG pathway enrichment analysis of RNA-seq showed that autophagy was enriched in differentially expressed genes upon GE treatment.
Discussion and conclusion
GE acts as an autophagic flux inhibitor, which may have potential chemotherapeutic use for NPC treatment and may have an application in basic research to explore the mechanisms of autophagy.
Institution photo archives are important digital resource with a large proportion of old photos, which makes them of great value in aspects of history and culture. Based on OAIS (Open Archival Information System) Model, the
Anhui University Memory Project (AMP) designed and realized a Long-term
Preservation Process, which included a series of standard procedures for lifecycle management. Then digital resource repository and digital memory site were developed according to demands of Anhui University for constructing and presenting memory. This paper aims to introduce the architecture and achievements of
AMP, as well as the design and implementation of long-term preservation process and two distinctive ways of resource organization and memory presentation.
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