Associations of air pollution and greenness with global burden of breast cancer: an ecological study.

Despite the significance of the associations of air pollution and greenness with the risk of breast cancer, this topic has not been investigated on a global scale. We conducted an ecological study using 7 years of data from 162 countries. Disability-adjusted life years (DALYs) and incidence data were used to represent the breast cancer disease burden. Particulate matter with a diameter < 2.5 µm (PM2.5), ozone (O3), nitrogen dioxide (NO2), and the normalized difference vegetation index (NDVI) were adopted as our exposures. We employed generalized linear mixed models to explore the relationship between air pollution and greenness on breast cancer disease burden. The rate ratio (RR) and its 95% confidence interval (CI) indicate the effect size. There is a positive association between air pollution and the burden of breast cancer disease. Contrarily, per interquartile range increment in NDVI was negatively associated with DALYs and incidence. In terms of air pollutants and breast cancer, NDVI seems to have a significant influence on the relationship between these two conditions. A higher amount of greenness helps to alleviate the negative association of air pollution on breast cancer. PM2.5 and O3 play a mediating role in the relationship between greenness and breast cancer disease burden. In areas with higher levels of greenness, there is a possibility that the inverse association between air pollutants and the burden of breast cancer may be influenced.

Effects of 4-tert-butylpyrocatechol and tea polyphenol on growth, physiology and antioxidant responses in Microcystis aeruginosa.

Global warming has increased the frequency of Microcystis aeruginosa blooms, leading to the deterioration of water quality and loss of biodiversity. Therefore, developing effective strategies for controlling M. aeruginosa blooms has become an important research topic. Plant extracts, 4­tert-butylpyrocatechol (TBC) and tea polyphenol (TP) are commonly used for water purification and to increase fish immunity, which have great potential to inhibit cyanobacterial blooms. The inhibitory effects of TBC and TP on M. aeruginosa were investigated in terms of growth characteristics, cell membrane morphology, physiological, photosynthetic activities, and antioxidant enzymes activities. The results showed that TBC and TP inhibited the growth of M. aeruginosa by decreasing the chlorophyll fluorescence transients or increasing the antioxidant enzymes activities of M. aeruginosa. TBC damaged the cell morphology of M. aeruginosa, reduced extracellular polysaccharides and protein contents, and up-regulated the antioxidant activity-related gene (sod and gsh) expressions of M. aeruginosa. TP significantly decreased the photosynthetic pigment content, influenced the phycobiliprotein content, and strongly down-regulated the photosynthesis-related gene (psbA, psaB, and rbcL) relative expressions of M. aeruginosa. TBC caused significant oxidative stress, dysfunction of physiological metabolic processes, and damaged crucial biomacromolecules (e.g., lipids, proteins and polysaccharides), prompted the loss of cell integrity, ultimately leading to the death of M. aeruginosa. However, TP depressed photosynthetic activities and consequently inhibited the transfer of electrons, affected the electron transfer chain, decreased the photosynthetic efficiency, and eventually caused the death of M. aeruginosa cells. Our study showed the inhibitory effects and algicidal mechanisms of TBC and TP on M. aeruginosa, and provide a theoretical basis for restrain the overgrowth of M. aeruginosa.

Multiple Impacts of Urban Built and Natural Environment on Lung Cancer Incidence: A Case Study in Bengbu.

Tumours are the main disease affecting the health of the Chinese population, and lung cancer is the malignancy with the highest incidence. Hence, the need to study and analyse the population of lung cancer incidence in order to effectively control and prevent it. In this research, we discuss the demographic characteristics of lung cancer incidence population of 2014 to 2020 from the perspective of multiple urban environmental factors, taking Bengbu city in the Huaihe River Basin of China as the research area, analyse the correlation between environmental indicators and lung cancer incidence population through the Spearman's rank correlation assessment model, and analyse the interaction between the influence factors of a geographic detector to analyse the influence of urban environmental factors. The results showed the followings: (1) The distribution characteristics of lung cancer incidence population were mainly geriatric population and spatially mainly fell in the old urban area of the study area, and the population distribution had clustered characteristics. (2) Through Spearman's rank correlation analysis, the land use, road traffic, spatial form, service facilities, and the open space of green space of the urban-built environment as well as the natural environment are all correlated with the incidence of lung cancer. (3) Factor detection and interaction analysis revealed a greater effect of spring and winter on lung cancer prevalence. In addition, the road intersection density and the distance to industrial are the most important potential influencing factors, and the interaction of any two factors will increase the risk of lung cancer.

KSHV-encoded ORF45 activates human NLRP1 inflammasome.

At steady state, the NOD-like receptor (NLR)-containing pyrin domain (PYD) (NLRP)1 inflammasome is maintained in an auto-inhibitory complex by dipeptidyl peptidases 8 and 9 (DPP8 and DPP9) and is activated by pathogen-encoded proteases after infection. Here, we showed that the open reading frame (ORF)45 protein of the Kaposi's sarcoma-associated herpesvirus activated the human NLRP1 (hNLRP1) inflammasome in a non-protease-dependent manner, and we additionally showed that the Linker1 region of hNLRP1, situated between the PYD and NACHT domains, was required for the auto-inhibition and non-protease-dependent activation of hNLRP1. At steady state, the interaction between Linker1 and the UPA subdomain silenced the activation of hNLRP1 in auto-inhibitory complexes either containing DPP9 or not in a manner independent of DPP9. ORF45 binding to Linker1 displaced UPA from the Linker1-UPA complex and induced the release of the C-terminal domain of hNLRP1 for inflammasome assembly. The ORF45-dependent activation of the NLRP1 inflammasome was conserved in primates but was not observed for murine NLRP1b inflammasomes.

The SUMO E3 ligase activity of ORF45 determines KSHV lytic replication.

RSK1, an essential cellular kinase for Kaposi's sarcoma-associated herpesvirus (KSHV) replication, is highly phosphorylated and SUMOylated during KSHV lytic cycle, which determine the substrate phosphorylation and specificity of RSK1, respectively. However, the SUMO E3 ligase responsible for attaching SUMO to RSK1 has not yet been identified. By genome-wide screening, we found that KSHV ORF45 is necessary and sufficient to enhance RSK1 SUMOylation. Mechanistically, KSHV ORF45 binds to SUMOs via two classic SUMO-interacting motifs (SIMs) and functions as a SIM-dependent SUMO E3 ligase for RSK1. Mutations on these ORF45 SIMs resulted in much lower lytic gene expressions, viral DNA replication, and mature progeny virus production. Interestingly, KSHV ORF45 controls RSK1 SUMOylation and phosphorylation via two separated functional regions: SIMs and amino acid 17-90, respectively, which do not affect each other. Similar to KSHV ORF45, ORF45 of Rhesus Macaque Rhadinovirus has only one SIM and also increases RSK1 SUMOylation in a SIM-dependent manner, while other ORF45 homologues do not have this function. Our work characterized ORF45 as a novel virus encoded SUMO E3 ligase, which is required for ORF45-RSK1 axis-mediated KSHV lytic gene expression.

RSK1 SUMOylation is required for KSHV lytic replication.

RSK1, a downstream kinase of the MAPK pathway, has been shown to regulate multiple cellular processes and is essential for lytic replication of a variety of viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV). Besides phosphorylation, it is not known whether other post-translational modifications play an important role in regulating RSK1 function. We demonstrate that RSK1 undergoes robust SUMOylation during KSHV lytic replication at lysine residues K110, K335, and K421. SUMO modification does not alter RSK1 activation and kinase activity upon KSHV ORF45 co-expression, but affects RSK1 downstream substrate phosphorylation. Compared to wild-type RSK1, the overall phosphorylation level of RxRxxS*/T* motif is significantly declined in RSK1K110/335/421R expressing cells. Specifically, SUMOylation deficient RSK1 cannot efficiently phosphorylate eIF4B. Sequence analysis showed that eIF4B has one SUMO-interacting motif (SIM) between the amino acid position 166 and 170 (166IRVDV170), which mediates the association between eIF4B and RSK1 through SUMO-SIM interaction. These results indicate that SUMOylation regulates the phosphorylation of RSK1 downstream substrates, which is required for efficient KSHV lytic replication.

Lysophosphatidic Acid Receptor 6 (LPAR6) Is a Potential Biomarker Associated with Lung Adenocarcinoma.

LPAR6 is the most recently determined G-protein-coupled receptor of the lysophosphatidic acid receptor, and very few of studies have demonstrated the performance of LPAR6 in cancers. Moreover, the relationship of LPAR6 to the potential of prognosis and tumor infiltration immune cells in different types of cancer are still unclarified. In this study, the mRNA expression of LPAR6 and its clinical characteristics were evaluated on various databases. The association between LPAR6 and immune infiltrates of various types of cancer were investigated via TIMER. Immunohistochemistry (IHC) for LPAR6 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissue microarray with patients' information was detected. We constructed a systematic prognostic landscape in a variety of types of cancer base on the expression level of mRNA. We enclosed that higher LPAR6 mRNA expression level was associated with better overall survival in some types of malignancy. Moreover, LPAR6 significantly affects the prognostic potential of various cancers in The Cancer Genome Atlas Program (TCGA), especially in lung cancer. Tissue microarrays of lung cancer patient cohorts demonstrated that a higher protein level of LPAR6 was correlated to better overall survival of LUAD rather than LUSC cohorts. Further research indicated that the underlying mechanism of this phenome might be the mRNA expression level of LPAR6 was positively associated to infiltrating statuses of devious immunocytes in LUAD rather than in LUSC, that is, LPAR6 expression potentially contributes to the activation and recruiting of T cells (CD8+ T, naive T, effector T cell) and NK cells and inactivates Tregs, decreases T cell exhaustion and regulates T-helper (Th) cells in LUAD. Our discovery implies that LPAR6 is associated with prognostic potential and immune-infiltrating levels in LUAD. These discoveries imply that LPAR6 could be a promising novel biomarker for indicating the prognosis potential of LUAD patients.

KSHV strategies for host dsDNA sensing machinery.

The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling. This review summarizes the evasion strategies of host cGAS DNA sensing pathway by Kaposi's Sarcoma-associated Herpesvirus (KSHV) and their contributions to KSHV life cycles.