Association of ambient ozone exposure and greenness exposure with hemorrhagic stroke mortality at different times: A cohort study in Shandong Province, China.

Evidence on the association between long-term ozone exposure and greenness exposure and hemorrhagic stroke (HS) is limited, with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone, greenness, and mortality from HS using exposure metrics at different times. We also examined whether greenness exposure modified the relationship between ozone exposure and mortality due to HS. The study population consisted of 45771 participants aged ≥40 y residing in 20 counties in Shandong Province who were followed up from 2013 to 2019. Ozone exposure metrics (annual mean and warm season) and the normalized difference a measure of greenness exposure, were calculated. The relationship between environmental exposures (ozone and greenness exposures) and mortality from HS was assessed using time-dependent Cox proportional hazards models, and the modification of greenness exposure was examined using stratified analysis with interaction terms. The person-years at the end of follow-up were 90,663. With full adjustments, the risk of death from hemorrhagic stroke increased by 5% per interquartile range increase in warm season ozone [hazard ratio =1.05; 95 % confidence interval: 1.01-1.08]. No clear association was observed between annual ozone and mortality HS. Both the annual and summer NDVI were found to reduce the risk of HS mortality. The relationships were influenced by age, sex, and residence (urban or rural). Furthermore, greenness exposure was shown to have a modifying effect on the relationship between ozone exposure and the occurrence of HS mortality (P for interaction = 0.001). Long-term exposure to warm season O3 was positively associated with HS mortality, while greenness exposure was inversely associated with HS mortality. Greenness exposure may mitigate the negative effects of warm season ozone exposure on HS mortality.

Effects of greenness in university campuses on test anxiety among Chinese university students during COVID-19 lockdowns: a correlational and mediation analysis.

The purpose of this study is to investigate the correlations of greenness exposure with test anxiety among university students during COVID-19 lockdowns and to explore their mechanisms. We conducted a cross-sectional study with 2609 university students in Anhui and Shandong provinces, China. We assessed perceived campus greenness using a five-point Likert scale for quality, visibility, abundance, usage, and accessibility. Objective greenness was estimated via average normalised difference vegetation index (NDVI) in 1,000-, 1,500-, and 2,000-m radius zones around each of the campuses. A generalised linear mixed model examined the associations between greenness and test anxiety and to evaluate the mediation effects of physical activity, body mass index (BMI), and air pollution. Results showed that higher NDVI1500-m correlated with lower test anxiety (OR = 0.871; 95% CI: 0.851, 0.891), physical activity may partially mediate this association. Increased campus greenness may alleviate test anxiety among Chinese university students.

Effect of neighbourhood greenness on the association between air pollution and risk of stroke first onset: A case-crossover study in shandong province, China.

BACKGROUND: Higher neighbourhood greenness is associated with beneficial health outcomes, and short-term exposure to air pollution is associated with an elevated risk of stroke onset. However, little is known about their interactions. METHODS: Daily data on stroke first onset were collected from 20 counties in Shangdong Province, China, from 2013 to 2019. The enhanced vegetation index (EVI) and concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were calculated for each individual at the village or community level based on their home address to measure their neighbourhood exposure to greenness and air pollution. EVI was categorised as low or high, and a time-stratified case-crossover design was used to estimate the percent excess risk (ER%) of stroke associated with short-term exposure to air pollution. We further stratified greenness on the basis of EVI values into quartiles and introduced interaction terms between air pollutant concentrations and the median EVI values of the quartiles to assess the effect of greenness on the associations between short-term exposure and stroke. RESULTS: Individuals living in the high-greenness areas had weaker associations between total stroke risk and exposure to NO2 (low greenness: ER% = 1.765% [95% CI 1.205%-2.328%]; high greenness: ER% = 0.368% [95% CI -0.252% to 0.991%]; P = 0.001), O3 (low greenness: 0.476% [95% CI 0.246%-0.706%]; high greenness: ER% = 0.085% [95% CI -0.156% to 0.327%]; P = 0.011), and SO2 (low greenness: 0.632% [95% CI 0.138%-1.129%]; high greenness: ER% = -0.177% [95% CI -0.782% to 0.431%]; P = 0.035). CONCLUSION: Residence in areas with higher greenness was related to weaker associations between air pollution and stroke risk, suggesting that effectively planning green spaces can improve public health.

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.

Association of greenness with the disease burden of lower respiratory infections and mediation effects of air pollution and heat: a global ecological study.

Exposure to greenness is increasingly linked to beneficial health outcomes, but the associations between greenness and the disease burden of lower respiratory infections (LRIs) are unclear. We used the normalized difference vegetation index (NDVI) and the leaf area index (LAI) to measure greenness and incidence, death, and disability-adjusted life years (DALYs) due to LRIs to represent the disease burden of LRIs. We applied a generalized linear mixed model to evaluate the association between greenness and LRI disease burden and performed a stratified analysis, after adjusting for covariates. Additionally, we assessed the potential mediating effects of fine particulate matter (PM2.5), ozone (O3), nitrogen dioxide (NO2), and heat on the association between greenness and the disease burden of LRIs. In the adjusted model, one 0.1 unit increase of NDVI and 0.5 increase in LAI were significantly inversely associated with incidence, death, and DALYs due to LRIs, respectively. Greenness was negatively correlated with the disease burden of LRIs across 15-65 age group, both sexes, and low SDI groups. PM2.5, O3, and heat mediated the effects of greenness on the disease burden of LRIs. Greenness was significantly negatively associated with the disease burden of LRIs, possibly by reducing exposure to air pollution and heat.

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.

Molecular characterization and antibacterial ability of galectin-3 and galectin-9 in Onychostoma macrolepis.

Galectins belong to the ß-galactoside binding protein family, which have conserved carbohydrate-recognition domains (CRDs) and participate in innate and acquired immunity in animals. In this study, two galectin genes were cloned from Onychostoma macrolepis, OmGal-3 (galectin-3) and OmGal-9 (galectin-9). The open reading frames (ORFs) of OmGal-3 and OmGal-9 contain 732 and 978 base pairs, encoding 243 and 325 amino acids, respectively. OmGal-3 contains a C-terminal CRD, but OmGal-9 contains an N-terminal CRD and a C-terminal CRD. Two galectins were expressed at varying levels in all tissues examined, with the liver showing the highest expression. The relative gene expression levels of OmGal-3 and OmGal-9 following Aeromonas hydrophila infection were significantly up-regulated in the liver and spleen, and OmGal-9 had a greater increase than OmGal-3. The recombinant OmGal-3 and OmGal-9 proteins (rOmGal-3 and rOmGal-9) were authenticated and verified by SDS-PAGE and western blotting. ROmGal-3 and rOmGal-9 agglutinated all tested bacteria, including 3 g-positive bacteria (Aeromonas hydrophila, Escherichia coli, and Vibrio parahaemolyticus) and 3 g-negative bacteria (Streptococcus agalactiae, Staphylococcus aureus, and Bacillus cereus) in vivo without Ca2+. ROmGal-3 showed strong binding both to gram-positive and gram-negative bacteria and OmGal-9 had a stronger binding activity against gram-positive bacteria. Furthermore, rOmGal-3 and rOmGal-9 exhibited dose-dependent binding capability to two classic pathogens associated molecular pattern (LPS and PGN) and two sugars (d-lactose and d-galactose), and rOmGal-3 has better binding activity at lower concentrations in LPS and PGN than rOmGal-3. The integrated analyses indicate that the two galectins probably play an important role in innate immune defense by binding to bacterial cells via the CRD domain against pathogen infection.

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.

ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 Replication.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent for the coronavirus disease 2019 (COVID-19) pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin 1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete autophagy response, elevated autophagosome formation but impaired autophagosome maturation, and declined autophagy by genetic knockout of essential autophagic genes reduces SARS-CoV-2 replication efficiency. By screening 26 viral proteins of SARS-CoV-2, we demonstrated that expression of ORF3a alone is sufficient to induce incomplete autophagy. Mechanistically, SARS-CoV-2 ORF3a interacts with autophagy regulator UVRAG to facilitate PI3KC3-C1 (Beclin-1-Vps34-Atg14) but selectively inhibit PI3KC3-C2 (Beclin-1-Vps34-UVRAG). Interestingly, although SARS-CoV ORF3a shares 72.7% amino acid identity with the SARS-CoV-2 ORF3a, the former had no effect on cellular autophagy response. Thus, our findings provide the mechanistic evidence of possible takeover of host autophagy machinery by ORF3a to facilitate SARS-CoV-2 replication and raise the possibility of targeting the autophagic pathway for the treatment of COVID-19.

Sensitive and rapid on-site detection of SARS-CoV-2 using a gold nanoparticle-based high-throughput platform coupled with CRISPR/Cas12-assisted RT-LAMP.

The outbreak of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic. The high infectivity of SARS-CoV-2 highlights the need for sensitive, rapid and on-site diagnostic assays of SARS-CoV-2 with high-throughput testing capability for large-scale population screening. The current detection methods in clinical application need to operate in centralized labs. Though some on-site detection methods have been developed, few tests could be performed for high-throughput analysis. We here developed a gold nanoparticle-based visual assay that combines with CRISPR/Cas12a-assisted RT-LAMP, which is called Cas12a-assisted RT-LAMP/AuNP (CLAP) assay for rapid and sensitive detection of SARS-CoV-2. In optimal condition, we could detect down to 4 copies/µL of SARS-CoV-2 RNA in 40 min. by naked eye. The sequence-specific recognition character of CRISPR/Cas12a enables CLAP a superior specificity. More importantly, the CLAP is easy for operation that can be extended to high-throughput test by using a common microplate reader. The CLAP assay holds a great potential to be applied in airports, railway stations, or low-resource settings for screening of suspected people. To the best of our knowledge, this is the first AuNP-based colorimetric assay coupled with Cas12 and RT-LAMP for on-site diagnosis of COVID-19. We expect CLAP assay will improve the current COVID-19 screening efforts, and make contribution for control and mitigation of the pandemic.

Analysis of Antibiotic Resistance Genes, Environmental Factors, and Microbial Community From Aquaculture Farms in Five Provinces, China.

The excessive use of antibiotics speeds up the dissemination and aggregation of antibiotic resistance genes (ARGs) in the environment. The ARGs have been regarded as a contaminant of serious environmental threats on a global scale. The constant increase in aquaculture production has led to extensive use of antibiotics as a means to prevent and treat bacterial infections; there is a universal concern about the environmental risk of ARGs in the aquaculture environment. In this study, a survey was conducted to evaluate the abundance and distributions of 10 ARGs, bacterial community, and environmental factors in sediment samples from aquatic farms distributed in Anhui (AP1, AP2, and AP3), Fujian (FP1, FP2, and FP3), Guangxi (GP1, GP2, and GP3), Hainan (HP1, HP2, and HP3), and Shaanxi (SP1, SP2, and SP3) Province in China. The results showed that the relative abundance of total ARGs was higher in AP1, AP2, AP3, FP3, GP3, HP1, HP2, and HP3 than that in FP1, FP2, GP1, GP2, SP1, SP2, and SP3. The sul1 and tetW genes of all sediment samples had the highest abundance. The class 1 integron (intl1) was detected in all samples, and the result of Pearson correlation analysis showed that the intl1 has a positive correlation with the sul1, sul2, sul3, bla OXA, qnrS, tetM, tetQ, and tetW genes. Correlation analysis of the bacterial community diversity and environmental factors showed that the Ca2+ concentration has a negative correlation with richness and diversity of the bacterial community in these samples. Of the identified bacterial community, Proteobacteria, Firmicutes, Chloroflexi, and Bacteroidota were the predominant phyla in these samples. Redundancy analysis showed that environmental factors (TN, TP, Cl-, and Ca2+) have a positive correlation with the bacterial community (AP1, GP1, GP2, GP3, SP1, SP2, and SP3), and the abundance of ARGs (sul1, tetW, qnrS, and intl1) has a positive correlation with the bacterial community (AP2, AP3, HP1, HP2, and HP3). Based on the network analysis, the ARGs (sul1, sul2, bla CMY, bla OXA, qnrS, tetW, tetQ, tetM, and intl1) were found to co-occur with bacterial taxa from the phyla Chloroflexi, Euryarchaeota, Firmicutes, Halobacterota, and Proteobacteria. In conclusion, this study provides an important reference for understanding the environmental risk associated with aquaculture activities in China.

Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. METHODS: Genome-wide screening was used to establish intraviral and viral-host interactomes. Quantitative proteomics was used to investigate the peripheral blood mononuclear cell (PBMC) proteome signature in COVID-19. FINDINGS: We elucidated 286 host proteins targeted by SARS-CoV-2 and >350 host proteins that are significantly perturbed in COVID-19-derived PBMCs. This signature in severe COVID-19 PBMCs reveals a significant upregulation of cellular proteins related to neutrophil activation and blood coagulation, as well as a downregulation of proteins mediating T cell receptor signaling. From the interactome, we further identified that non-structural protein 10 interacts with NF-κB-repressing factor (NKRF) to facilitate interleukin-8 (IL-8) induction, which potentially contributes to IL-8-mediated chemotaxis of neutrophils and the overexuberant host inflammatory response observed in COVID-19 patients. CONCLUSIONS: Our study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks but it also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms, representing a powerful resource in the pursuit of therapeutic interventions. FUNDING: National Key Research and Development Project of China, National Natural Science Foundation of China, National Science and Technology Major Project, Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission, Shanghai Municipal Key Clinical Specialty, Innovative Research Team of High-level Local Universities in Shanghai, Interdisciplinary Program of Shanghai Jiao Tong University, SII Challenge Fund for COVID-19 Research, Chinese Academy of Sciences (CAS) Large Research Infrastructure of Maintenance and Remolding Project, and Chinese Academy of Sciences Key Technology Talent Program.

The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis.

Zika virus (ZIKV) causes microcephaly and disrupts neurogenesis. Dicer-mediated miRNA biogenesis is required for embryonic brain development and has been suggested to be disrupted upon ZIKV infection. Here we mapped the ZIKV-host interactome in neural stem cells (NSCs) and found that Dicer is specifically targeted by the capsid from ZIKV, but not other flaviviruses, to facilitate ZIKV infection. We identified a capsid mutant (H41R) that loses this interaction and does not suppress Dicer activity. Consistently, ZIKV-H41R is less virulent and does not inhibit neurogenesis in vitro or corticogenesis in utero. Epidemic ZIKV strains contain capsid mutations that increase Dicer binding affinity and enhance pathogenicity. ZIKV-infected NSCs show global dampening of miRNA production, including key miRNAs linked to neurogenesis, which is not observed after ZIKV-H41R infection. Together these findings show that capsid-dependent suppression of Dicer is a major determinant of ZIKV immune evasion and pathogenesis and may underlie ZIKV-related microcephaly.

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.

[Influence of scald and lipopolysaccharide on gastrointestinal motility].

OBJECTIVE: To investigate the pathogenesis of gastrointestinal motility dysfunction as a result of scald and lipopolysaccharide (LPS) challenge in guinea pigs. METHODS: Thirty guinea pigs were enrolled in the study and were randomly divided into 3 groups:i. e. control (n = 10, with intraperitoneal injection of isotonic saline), scald (n = 10, with 30% TBSA deep partial thickness burn) and LPS (n = 10, with intraperitoneal injection of LPS) groups. Thirty minutes after treatment, all animals were gavaged with carbolic ink. The propelled distance of the ink within the gastrointestinal tract was measured. The intestinal tissue was harvested and homogenized, and the contents of CGRP, Na+-K+-ATP enzyme, Mg2+-ATP enzyme, Ca2+-ATP enzyme, Ca2+-Mg2+-ATP enzyme were determined, and the delta phim of haustra coli smooth muscular cell mitochondria was assessed. RESULTS: The propelled distance of the ink in the gastrointestinal tract in scald (53 +/- 9 cm) and LPS (91 +/- 10 cm) groups was obviously shorter than that in control group (142 +/- 11 cm, P < 0.01). Furthermore, the distance in scald group was shorter than that in LPS group (P < 0.01). The CGRP content in scald and LPS groups [52.0 +/- 39.0 microg/L and 20.0 +/- 23.0 microg/L] was obviously higher than that in control group (0.8 +/-2.0 microg/L, P <0.05 or 0.01), especially in scald group ( P < 0.05). The Na+-K+-ATP enzyme, Mg2+-ATP enzyme, Ca2+-ATP enzyme, Ca2+-Mg2+-ATP enzyme and the delta phim in scald and LPS groups were remarkably lower than those in control group (P <0.005), but there was no difference between scald and LPS groups (P > 0.05). CONCLUSION: The gastrointestinal motility of guinea pigs could obviously be inhibited by scald and LPS, especially by scald. LPS might be the key factor to produce change in the membrane potential of mitochondria of intestinal smooth muscle after severe scald.

[An experimental study on the prevention and treatment of postburn intestinal injury and bacterial translocation by Sijunzi decoction in scalded rats].

OBJECTIVE: To explore the effects of traditional Chinese herbal medicine Sijunzi decoction on amelioration of postburn intestinal injury in scalded rats. METHODS: One hundred and eighty Wistar rats were randomly divided into 3 groups, i.e. scald and treatment (T), scald control (S) and normal control (C) groups. The rats in T group were gavaged with the decoction consisting of tangshen, tuckahoe, large head atractylodes rhizome, glycyrrhizic and rhubarb in a dose of 2 ml twice daily, while the rats in C group were just gavaged with the same amount of distilled water. The rats were sacrificed according to the scheduled postburn observation timepoints. The contents of TNF, NO, MDA and ATPase activity in rat plasma and the intestinal mucosa and the S-IgA content in the intestinal mucus were determined respectively. The changes in histopathology of intestinal mucosa were observed. The samples from internal organ tissue and blood were obtained for bacterial culture. RESULTS: The contents of TNF, NO and MDA in the intestinal mucosa tissue and the rat plasma in scalded rats were lowered significantly by Sijunzi decoction. Furthermore, S-IgA secretion from intestinal mucous cells was maintained by Sijunzi decoction. T cell count was recovered and intestinal mucous barrier injury were lessened, and the bacterial positive rate in the internal organs was decreased. CONCLUSION: Traditional Chinese herbal medicine Sijunzi decoction might be helpful in alleviation of postburn intestinal injury and in the prevention of intestinal bacterial translocation.