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Human papillomavirus (HPV) is a DNA virus that causes sexually transmitted infections. The HPV oncoprotein E7 plays a critical role in the regulation of host immunity to promote the immune escape of HPV and the occurrence of cervical cancer or genital warts. Pyroptosis, a highly inflammatory form of programmed cell death, can be induced by inflammasomes and acts as a defense against pathogenic infection. However, whether HPV E7 can regulate cell pyroptosis to evade immune surveillance has not been determined. In this study, we found that HPV E7 could inhibit cell pyroptosis induced by transfection with dsDNA. The activation of the inflammasome, and the production of IL-18 and IL-1β were also restrained by HPV E7. Mass spectrometry and immunoprecipitation showed that HPV E7 interacted with IFI16 and TRIM21. We also discovered that HPV E7 recruited the E3 ligase TRIM21 to ubiquitinate and degrade the IFI16 inflammasome, leading to the inhibition of cell pyroptosis and self-escape from immune surveillance. Thus, our study reveals an important immune escape mechanism in HPV infection and may provide targets for the development of a novel immunotherapeutic strategy to effectively restore antiviral immunity.

Psoriasis, the most common skin inflammatory disease, is characterized by massive keratinocyte proliferation and immune cell infiltration into epidermis. L-Theanine (L-THE), a nonproteinogenic amino acid derived from green tea (Camellia sinensis), has been proved to possess the properties of anti-inflammatory, antidepressants and neuroprotective. However, whether L-THE has a therapeutic effect on psoriasis is still unknown. In this study, we found that the epidermal thickness and inflammatory response were significantly reduced in Imiquimod (IMQ)-induced psoriasis mice by applying with L-THE on mice skin. The expression of proliferation and inflammation associated genes such as keratin 17, IL-23 and CXCL1-3 was also downregulated by L-THE. Furthermore, L-THE inhibited the production of IL-23 in dendritic cells (DCs) after IMQ treatment, and decreased the levels of chemokines in keratinocytes treated with IL-17A by downregulating the expression of IL-17RA. RNA-seq and KEGG analysis revealed that L-THE significantly regulated the expression of IL-17A and NF-κB signaling pathway-associated genes. Metabolomics analysis displayed that L-THE promoted propanoate metabolism which has been reported to inhibit the activity of TH17 cells. Therefore, our results demonstrated that L-THE significantly decreases the levels of IL-23 and chemokines, and attenuates IMQ-induced psoriasis like skin inflammation by inhibiting the activation of NF‐κB and IL-17A signaling pathways, and promoting the propanoate metabolism. Our findings suggest that topical applied L-THE can be used as a topical drug candidate for the treatment of psoriasis or as an adjuvant treatment of ustekinumab or secukinumab to prevent the relapse of psoriasis.

Pavements are closely related to the livelihoods of urban residents as an important part of the urban road system. Based on the early field measurements of our team, we found that plant spacing, pavement orientation, and pavement material influence the pavement thermal environment. Our objective was to quantitatively evaluate the influence of various factors on pavements in Guangzhou along West Zhonghuan Road, Guangzhou University. Based on our team’s previous research, environment-met (ENVI-MET) numerical simulation software was used to simulate pavements under different road orientations, underlying surface materials, and plant distances. Quantitative analysis of the effects of different factor combinations on the temperature, humidity, wind speed, physiological equivalent temperature (PET), and radiant temperature (Tmrt) was performed. The results show that among the various factors affecting the thermal environment of pavement, street tree spacing was found to have the greatest effect on the thermal environment of pavement. The effect of direction is negligible; however, it has a significant effect on the wind speed. There was no significant difference in the air temperature and relative humidity between concrete and asphalt. The average air temperature of red floor tile was slightly lower than that of asphalt and concrete. Reducing the spacing of street trees can effectively reduce the penetration of direct solar radiation, physiological equivalent temperature (PET), and temperature (Tmrt) and improve pedestrian walking comfort. The results can serve as a reference for pavement design in Guangzhou and improve the wellbeing of citizens and promote environmental sustainability.

Carrier transport behavior in the perovskite light absorption layer significantly impacts the performance of perovskite solar cells (PSCs). In this work, reduced carrier recombination losses were achieved by the design of a band structure in perovskite materials. An ultrathin (PbI2/PbBr2)n film with a gradient thickness ratio was deposited as the lead halide precursor layer by a thermal evaporation method, and PSCs with a gradient band structure in the perovskite absorption layer were fabricated by a two-step method in ambient atmosphere. For comparison, PSCs with homogeneous perovskite materials of MAPbI3 and MAPbIxBr3 − x were fabricated as well. It is found that the gradient type-II band structure greatly reduces the carrier lifetime and enhances the carrier separation efficiency. As a result, the PSCs with a gradient band structure exhibit an average power conversion efficiency of 17.5%, which is 1–2% higher than that of traditional PSCs. This work provides a novel method for developing high-efficiency PSCs.

Stimulator of interferon genes (STING) is a central and multifaceted mediator in the innate immune response of higher vertebrates. To explore its role in teleost fish, the STING homolog of black carp (Mylopharyngodon piceus) (bcSTING) has been cloned and characterized in this paper. bcSTING transcription in Mylopharyngodon piceus fin (MPF) cells increased remarkably in response to GCRV and SVCV infection, or poly (I:C) stimulation. bcSTING migrated around 42 KDa in immunoblot assay and was identified as a cytosolic protein locating on ER majorly through immunofluorescence staining. Under condition of SVCV/GCRV infection or poly (I:C) stimulation, the subcellular distribution of bcSTING majorly displayed on mitochondria, which overlapped with that of bcMAVS. HA-bcSTING instead of bcSTING-HA presented strong IFN-inducing activity in reporter assay and antiviral ability against both SVCV and GCRV in plaque assay. Site mutation of serine (S) on C-terminus of bcSTING demonstrated that both S371 and S379 were crucial for its mediated signaling. Taken together, our study support the conclusion that bcSTING plays an important role in host innate immune defense against RNA virus such as SVCV and GCRV, in which its C-terminus functions crucially.

TAK1-binding protein 1 (TAB1) forms the protein complex with TAK1 and enhances its kinase activity in human and mammals. To elucidate the role of TAB1 in the innate immunity of teleost sfih, the TAB1 homologue of black carp (Mylopharyngodon piceus) (bcTAB1) has been cloned and characterized in this paper. bcTAB1 is composed of 498 amino acids and contains a typical PP2Cc domain like its mammalian counterpart. The transcription of bcTAB1 gene in vivo and ex vivo varied in response to different stimuli; and the immunofluorescence staining showed that bcTAB1 was distributed in both cytoplasm and nucleus of host cell. The reporter assay showed that neither bcTAB1-expression alone nor co-expression of bcTAB1 and bcTAK1 could activate the transcription of IFN in EPC cells. Accordingly, EPC cells expressing bcTAB1 or co-expressing bcTAB1 and bcTAK1 showed no improved antiviral activity against grass carp reovirus (GCRV) and spring viremia of carp virus (SVCV). However, EPC cells co-expressing bcTAB1, bcTAK1 and bcIRF7 showed fiercely increased IFN-inducing ability in reporter assay and obviously improved antiviral activity in plaque assay compared with EPC cells co-expressing bcTAK1 and bcIRF7. The subsequent co-immunoprecipitation assay identified that bcTAB1 associated with bcTAK1 but not interacted with bcIRF7. Based on our previous finding that bcTAK1 up-regulates bcIRF7-mediated IFN signaling during host innate immune activation, the data generated in this study support the conclusion that bcTAB1 interacts with bcTAK1 and boosts bcTAK1-activated bcIRF7/IFN signaling during host antiviral innate immune response against GCRV and SVCV.

NOD-like receptor (NLR) family member X1 (NLRX1) of human localizes on mitochondria and serves as a negative regulator of antiviral signaling. However, the function of NLRX1 in teleost fish still remains elusive. To explore its role in the innate immunity of teleost fish, NLRX1 homologue has been cloned and characterized from black carp (Mylopharyngodon piceus). Black carp NLRX1 (bcNLRX1) consists of 1008 amino acids, which includes a N-terminal mitochondrial targeting sequence, a central NACHT domain and a C-terminal leucine-rich repeat (LRR) domain. bcNLRX1 was identified as a cytosolic protein locating on mitochondria through immunofluorescence (IF) staining. The overlapped subcellular distribution of bcNLRX1 and black carp MAVS (bcMAVS) was detected in IF staining, and the direct interaction between these two molecules in vitro was identified through co-immunoprecipitation assay. When co-expressed with bcMAVS, bcNLRX1 fiercely reduced bcMAVS-mediated IFN induction in reporter assay. Accordingly, the antiviral activity of bcMAVS against both grass carp reovirus (GCRV) and spring viremia of carp virus (SVCV) was forcefully repressed by bcNLRX1 in plaque assay. Mutagenic analyses further revealed that the NACHT domain of bcNLRX1 was essential for it to interact with bcMAVS and to suppress bcMAVS-mediated antiviral signaling. Taken together, our data support the conclusion that bcNLRX1 negatively regulates bcMAVS-mediated antiviral signaling through its NACHT domain during host innate immune activation.

Imiquimod (IMQ) is approved as a first-line treatment for genital warts caused by human papillomavirus (HPV) infection. However, the recurrence rate is very high. HPV E7 protein plays a critical role in HPV immune escape. However, the role of HPV11 E7 protein in genital warts recurrence during IMQ treatment is not clear. Here, we found that the expression profile of NHEK cells was obviously changed after IMQ treatment, and a large number of genes encoding cytokines and genes involved in cytokine-mediated signaling pathways and cellular metabolic signaling pathways were up- or downregulated. HPV11E7 overexpression inhibited the IMQ-induced production of of multiple chemokines and colony-stimulating factors in NHEK cells. Furthermore, we found that HPV11E7 could impair the activation of mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, our results suggested that HPV11 E7 diminishes the production of chemokines, colony-stimulating factors and other cytokines via inhibition of the MAPK signaling pathway, which suppresses the therapeutic effect of IMQ and promotes the recurrence of diseases, such as condyloma acuminatum.